[{"Name":"Introduction to Enzymes","TopicPlaylistFirstVideoID":0,"Duration":null,"Videos":[{"Watched":false,"Name":"The History of Enzymes","Duration":"4m 3s","ChapterTopicVideoID":28564,"CourseChapterTopicPlaylistID":286641,"HasSubtitles":true,"ThumbnailPath":null,"UploadDate":null,"DurationForVideoObject":null,"Description":null,"MetaTitle":null,"MetaDescription":null,"Canonical":null,"VideoComments":[],"Subtitles":[{"Start":"00:00.000 ","End":"00:03.000","Text":"Welcome to the chapter on enzymes."},{"Start":"00:03.000 ","End":"00:07.485","Text":"We\u0027re going to introduce enzymes and start with the history of enzymes."},{"Start":"00:07.485 ","End":"00:08.970","Text":"By the end of this section,"},{"Start":"00:08.970 ","End":"00:11.610","Text":"you will know the history of enzyme studies and"},{"Start":"00:11.610 ","End":"00:16.245","Text":"understanding and the contributors to the understanding of enzymes."},{"Start":"00:16.245 ","End":"00:21.765","Text":"Biological catalysis was first recognized in the late 1700s,"},{"Start":"00:21.765 ","End":"00:26.370","Text":"in studies on the digestion of meat by secretions of the stomach."},{"Start":"00:26.370 ","End":"00:30.030","Text":"Research continued in the 1800s with"},{"Start":"00:30.030 ","End":"00:35.355","Text":"examinations of the conversion of starch to sugar by saliva and various plant extracts."},{"Start":"00:35.355 ","End":"00:38.100","Text":"Now let\u0027s mention a name you probably all know."},{"Start":"00:38.100 ","End":"00:40.080","Text":"In the 1850s,"},{"Start":"00:40.080 ","End":"00:43.580","Text":"Louis Pasteur concluded that fermentation of sugar"},{"Start":"00:43.580 ","End":"00:47.435","Text":"into alcohol by yeast is catalyzed by ferments."},{"Start":"00:47.435 ","End":"00:50.420","Text":"He suggested that these ferments were"},{"Start":"00:50.420 ","End":"00:54.185","Text":"inseparable from the structure of living yeast cells."},{"Start":"00:54.185 ","End":"01:00.215","Text":"This view called vitalism, prevailed for decades."},{"Start":"01:00.215 ","End":"01:03.875","Text":"Then, in 1897, Eduard Buchner"},{"Start":"01:03.875 ","End":"01:07.954","Text":"discovered that yeast extracts could ferment sugar to alcohol,"},{"Start":"01:07.954 ","End":"01:10.610","Text":"proving that fermentation was promoted by molecules"},{"Start":"01:10.610 ","End":"01:13.430","Text":"that continued to function when removed from cells."},{"Start":"01:13.430 ","End":"01:16.400","Text":"This experiment marked the end of vitalistic notions"},{"Start":"01:16.400 ","End":"01:19.690","Text":"in the beginning of a science of biochemistry."},{"Start":"01:19.690 ","End":"01:24.470","Text":"Frederich W. Kuhne later called these molecules that were detected by"},{"Start":"01:24.470 ","End":"01:30.610","Text":"Buchner enzymes from the Greek word emzymos, which means leavened."},{"Start":"01:30.610 ","End":"01:33.980","Text":"We started the 1700s with a study of digestion of meat."},{"Start":"01:33.980 ","End":"01:35.840","Text":"In the 1800s,"},{"Start":"01:35.840 ","End":"01:39.920","Text":"examinations of starch to sugar was"},{"Start":"01:39.920 ","End":"01:44.945","Text":"studied and further hinted on the idea of enzymes and in the 1850s,"},{"Start":"01:44.945 ","End":"01:51.515","Text":"Louis Pasteur concluded that fermentation was catalyzed by ferments."},{"Start":"01:51.515 ","End":"01:53.990","Text":"This led to the idea of vitalism,"},{"Start":"01:53.990 ","End":"01:56.300","Text":"which was the belief that these ferments were"},{"Start":"01:56.300 ","End":"02:00.215","Text":"inseparable from the living cells and in 1897,"},{"Start":"02:00.215 ","End":"02:02.150","Text":"Eduard Buchner discovered that,"},{"Start":"02:02.150 ","End":"02:08.825","Text":"they actually can be separated and continue the function when removed from cells."},{"Start":"02:08.825 ","End":"02:13.190","Text":"This is where vitalism came to"},{"Start":"02:13.190 ","End":"02:19.100","Text":"its combination and biochemistry took over the idea of enzymes,"},{"Start":"02:19.100 ","End":"02:22.955","Text":"the term as coined by Frederich Kuhne."},{"Start":"02:22.955 ","End":"02:26.360","Text":"Now as vitalistic notions of life were disproved the isolation of"},{"Start":"02:26.360 ","End":"02:27.950","Text":"new enzymes and the investigation of"},{"Start":"02:27.950 ","End":"02:30.755","Text":"their properties advance the science of biochemistry."},{"Start":"02:30.755 ","End":"02:34.640","Text":"The isolation and crystallization of urease by James Sumner"},{"Start":"02:34.640 ","End":"02:38.990","Text":"in 1926 provided a breakthrough in early enzyme studies."},{"Start":"02:38.990 ","End":"02:44.195","Text":"Sumner found that urease crystals consisted entirely"},{"Start":"02:44.195 ","End":"02:49.510","Text":"of protein and he postulated that all enzymes are proteins."},{"Start":"02:49.510 ","End":"02:51.590","Text":"In the absence of other examples,"},{"Start":"02:51.590 ","End":"02:56.390","Text":"the idea remain controversial for some time only in the 1930s was"},{"Start":"02:56.390 ","End":"02:59.420","Text":"Sumner\u0027s conclusion widely accepted after"},{"Start":"02:59.420 ","End":"03:03.530","Text":"John Northrop and Moses Kunitz crystallized pepsin,"},{"Start":"03:03.530 ","End":"03:08.900","Text":"trypsin, and other digestive enzymes and found them also to be proteins."},{"Start":"03:08.900 ","End":"03:13.895","Text":"Now although the molecular nature of enzymes was not yet fully appreciated,"},{"Start":"03:13.895 ","End":"03:17.945","Text":"JBS Haldane, who during this period wrote a paper entitled Enzymes,"},{"Start":"03:17.945 ","End":"03:22.520","Text":"made the remarkable suggestion that weak bonding and actions between"},{"Start":"03:22.520 ","End":"03:27.605","Text":"an enzyme and its substrate might be used to catalyze a reaction."},{"Start":"03:27.605 ","End":"03:32.900","Text":"This insight lies at the heart of our current understanding of enzymatic catalysis,"},{"Start":"03:32.900 ","End":"03:40.325","Text":"that there\u0027s an enzyme and a substrate and they fit like a lock and key."},{"Start":"03:40.325 ","End":"03:43.850","Text":"Now since the latter part of the 20th century,"},{"Start":"03:43.850 ","End":"03:46.070","Text":"research on enzymes has been intensive."},{"Start":"03:46.070 ","End":"03:48.500","Text":"It has led to the purification of thousands of enzymes,"},{"Start":"03:48.500 ","End":"03:51.830","Text":"elucidation of the structure and chemical mechanism of many of them,"},{"Start":"03:51.830 ","End":"03:54.065","Text":"and a general understanding of how enzymes work."},{"Start":"03:54.065 ","End":"03:57.770","Text":"We will learn about all this in the coming chapter and with this,"},{"Start":"03:57.770 ","End":"04:03.750","Text":"we concluded the history of enzymes within the introduction to enzymes."}],"ID":30092},{"Watched":false,"Name":"Exercise 1","Duration":"2m 54s","ChapterTopicVideoID":28565,"CourseChapterTopicPlaylistID":286641,"HasSubtitles":true,"ThumbnailPath":null,"UploadDate":null,"DurationForVideoObject":null,"Description":null,"MetaTitle":null,"MetaDescription":null,"Canonical":null,"VideoComments":[],"Subtitles":[{"Start":"00:00.000 ","End":"00:06.285","Text":"Welcome to exercises on the history of enzymes within the introduction to enzymes."},{"Start":"00:06.285 ","End":"00:08.550","Text":"A general and specific outline of the history of"},{"Start":"00:08.550 ","End":"00:11.190","Text":"discovery of enzymes is described in this lesson."},{"Start":"00:11.190 ","End":"00:13.245","Text":"Answer the following questions."},{"Start":"00:13.245 ","End":"00:17.070","Text":"What was first recognized and described in the late 1700s and"},{"Start":"00:17.070 ","End":"00:21.450","Text":"studies on the digestion of meat by secretions of the stomach?"},{"Start":"00:21.450 ","End":"00:28.785","Text":"B,what did Eduard Buchner discover in 1897 and what was its significance?"},{"Start":"00:28.785 ","End":"00:33.915","Text":"C, what did Frederick W. Kuhne contribute to the topic?"},{"Start":"00:33.915 ","End":"00:37.580","Text":"Let\u0027s start with A, what was first recognized and described in"},{"Start":"00:37.580 ","End":"00:44.600","Text":"the late 1700s in studies on the digestion of meat by secretions of the stomach?"},{"Start":"00:44.600 ","End":"00:50.315","Text":"Biological catalysis was first recognized and described in the late 1700s."},{"Start":"00:50.315 ","End":"00:57.450","Text":"The digestion of meat by secretions of the stomach was what led to this discovery."},{"Start":"00:57.450 ","End":"01:03.635","Text":"B, what did Eduard Buchner discover in 1897 and what was its significance?"},{"Start":"01:03.635 ","End":"01:06.830","Text":"In 1897, Eduard Buchner discovered that"},{"Start":"01:06.830 ","End":"01:10.759","Text":"cell-free yeast extracts could ferment sugar to alcohol,"},{"Start":"01:10.759 ","End":"01:12.800","Text":"proving that fermentation was promoted by"},{"Start":"01:12.800 ","End":"01:15.965","Text":"molecules that continued to function when removed from cells."},{"Start":"01:15.965 ","End":"01:18.440","Text":"This experiment mark the end of"},{"Start":"01:18.440 ","End":"01:23.195","Text":"vitalistic notions and the beginning of the science of biochemistry."},{"Start":"01:23.195 ","End":"01:27.620","Text":"Now the significance of this was that this experiment"},{"Start":"01:27.620 ","End":"01:32.134","Text":"marked the end of vitalistic notions and the beginning of the signs of biochemistry."},{"Start":"01:32.134 ","End":"01:39.005","Text":"The idea of vitalistic notions was that the biochemical catalysis was dependent on cells."},{"Start":"01:39.005 ","End":"01:42.590","Text":"This was very significant to realize that"},{"Start":"01:42.590 ","End":"01:46.999","Text":"cell-free extracts could continue with this biological catalysis."},{"Start":"01:46.999 ","End":"01:52.779","Text":"As for C, Frederick W. Kuhne called these molecules that were detected by Buchner,"},{"Start":"01:52.779 ","End":"01:54.645","Text":"enzymes from the Greek word,"},{"Start":"01:54.645 ","End":"01:57.720","Text":"enzymos, which means leavened."},{"Start":"01:57.720 ","End":"02:02.115","Text":"He coined the term enzymes."},{"Start":"02:02.115 ","End":"02:06.080","Text":"We look at the 3 main things that we talked about here."},{"Start":"02:06.080 ","End":"02:09.200","Text":"We started with the late 1700s"},{"Start":"02:09.200 ","End":"02:12.995","Text":"based on the studies of digestion of meat by secretions of the stomach."},{"Start":"02:12.995 ","End":"02:17.440","Text":"Biological catalysis was first recognized, thanks to this."},{"Start":"02:17.440 ","End":"02:20.970","Text":"Next 1897, Eduard Buchner,"},{"Start":"02:20.970 ","End":"02:25.400","Text":"he discovered that cell-free yeast extracts could ferment sugar to alcohol."},{"Start":"02:25.400 ","End":"02:31.715","Text":"Meaning that the idea of vitalistic notions that was dependent on the presence of cells,"},{"Start":"02:31.715 ","End":"02:40.150","Text":"now were actually no longer the leading belief with regard to biological catalysis."},{"Start":"02:40.150 ","End":"02:44.330","Text":"Third thing we talked about was Frederick Kuhne,"},{"Start":"02:44.330 ","End":"02:51.420","Text":"who coined the term enzymes based on enzymos from Greek, which means leavened."}],"ID":30093},{"Watched":false,"Name":"Exercise 2","Duration":"45s","ChapterTopicVideoID":28566,"CourseChapterTopicPlaylistID":286641,"HasSubtitles":true,"ThumbnailPath":null,"UploadDate":null,"DurationForVideoObject":null,"Description":null,"MetaTitle":null,"MetaDescription":null,"Canonical":null,"VideoComments":[],"Subtitles":[{"Start":"00:00.000 ","End":"00:03.749","Text":"We\u0027re back with another exercise within the history of enzymes."},{"Start":"00:03.749 ","End":"00:07.724","Text":"How did crystallization techniques contribute to the study of enzymes?"},{"Start":"00:07.724 ","End":"00:11.850","Text":"The isolation and crystallization of urease by James Sumner in"},{"Start":"00:11.850 ","End":"00:16.499","Text":"1926 provided a breakthrough in early enzyme studies."},{"Start":"00:16.499 ","End":"00:21.030","Text":"Sumner found that urease crystals consisted entirely of"},{"Start":"00:21.030 ","End":"00:25.590","Text":"protein and he postulated that all enzymes are proteins."},{"Start":"00:25.590 ","End":"00:27.300","Text":"In the 1930s,"},{"Start":"00:27.300 ","End":"00:31.859","Text":"John Northrop and Moses Kunitz crystallized pepsin, trypsin,"},{"Start":"00:31.859 ","End":"00:34.860","Text":"and other digestive enzymes and found them also to be"},{"Start":"00:34.860 ","End":"00:38.625","Text":"proteins which substantiated Sumner\u0027s thoughts."},{"Start":"00:38.625 ","End":"00:42.004","Text":"With this, we completed another exercise within"},{"Start":"00:42.004 ","End":"00:46.830","Text":"the history of the study of enzymes and introduction to enzymes."}],"ID":30094},{"Watched":false,"Name":"Enzyme Components-Most Enzymes are Proteins","Duration":"6m 20s","ChapterTopicVideoID":28585,"CourseChapterTopicPlaylistID":286641,"HasSubtitles":true,"ThumbnailPath":null,"UploadDate":null,"DurationForVideoObject":null,"Description":null,"MetaTitle":null,"MetaDescription":null,"Canonical":null,"VideoComments":[],"Subtitles":[{"Start":"00:00.000 ","End":"00:03.630","Text":"We are within introduction to enzymes in the chapter on enzymes,"},{"Start":"00:03.630 ","End":"00:05.730","Text":"and we\u0027re going to talk about enzyme components."},{"Start":"00:05.730 ","End":"00:07.184","Text":"By the end of this section,"},{"Start":"00:07.184 ","End":"00:11.520","Text":"you\u0027ll be able to understand enzyme components and general composition of enzymes,"},{"Start":"00:11.520 ","End":"00:15.090","Text":"and contributory factors to enzyme catalytic activity."},{"Start":"00:15.090 ","End":"00:18.900","Text":"With the exception of this small group of catalytic RNA molecules,"},{"Start":"00:18.900 ","End":"00:21.165","Text":"all enzymes are proteins."},{"Start":"00:21.165 ","End":"00:24.660","Text":"Their catalytic activity depends on the integrity of"},{"Start":"00:24.660 ","End":"00:28.380","Text":"their native protein conformation. What does this mean?"},{"Start":"00:28.380 ","End":"00:33.783","Text":"If an enzyme is denatured or dissociated into its subunits,"},{"Start":"00:33.783 ","End":"00:37.200","Text":"catalytic activity is usually lost."},{"Start":"00:37.200 ","End":"00:41.145","Text":"If an enzyme is broken down into its component amino acids,"},{"Start":"00:41.145 ","End":"00:45.105","Text":"its catalytic activity is always destroyed."},{"Start":"00:45.105 ","End":"00:47.145","Text":"Thus, the primary,"},{"Start":"00:47.145 ","End":"00:48.390","Text":"secondary, tertiary,"},{"Start":"00:48.390 ","End":"00:53.400","Text":"and quaternary structures of protein enzymes are essential to their catalytic activity."},{"Start":"00:53.400 ","End":"01:00.180","Text":"This means the structure of the protein as it\u0027s folded on itself,"},{"Start":"01:00.180 ","End":"01:02.505","Text":"so the sequence of the amino acids,"},{"Start":"01:02.505 ","End":"01:04.695","Text":"the way they interact with each other,"},{"Start":"01:04.695 ","End":"01:06.645","Text":"the tertiary structure,"},{"Start":"01:06.645 ","End":"01:09.540","Text":"the interactions of the different parts of"},{"Start":"01:09.540 ","End":"01:13.050","Text":"this protein as it folds and a quaternary, or the subunits,"},{"Start":"01:13.050 ","End":"01:16.890","Text":"that associate and contribute to the enzyme that"},{"Start":"01:16.890 ","End":"01:21.370","Text":"is a protein are essential to their catalytic activity."},{"Start":"01:21.370 ","End":"01:23.660","Text":"Enzymes like other proteins,"},{"Start":"01:23.660 ","End":"01:31.265","Text":"have molecular weights ranging from 12,000 to 1 million and even to more than 1 million."},{"Start":"01:31.265 ","End":"01:35.780","Text":"Some enzymes require no additional chemical groups for"},{"Start":"01:35.780 ","End":"01:40.489","Text":"activity other than the amino acid residues alone,"},{"Start":"01:40.489 ","End":"01:43.340","Text":"meaning only the amino acids that make up"},{"Start":"01:43.340 ","End":"01:47.420","Text":"the protein are needed for that enzyme function."},{"Start":"01:47.420 ","End":"01:53.420","Text":"Other enzymes require an additional chemical component called a cofactor."},{"Start":"01:53.420 ","End":"01:59.525","Text":"You could see here some inorganic elements that serve as cofactors for enzymes."},{"Start":"01:59.525 ","End":"02:04.760","Text":"You see Cu^2 plus, Fe^2 plus or Fe^3 plus, K plus etc."},{"Start":"02:04.760 ","End":"02:08.810","Text":"Now, the cofactor is either one or more"},{"Start":"02:08.810 ","End":"02:15.440","Text":"inorganic ions or a complex organic or metalorganic molecule called a coenzyme."},{"Start":"02:15.440 ","End":"02:18.740","Text":"You see here examples of coenzymes."},{"Start":"02:18.740 ","End":"02:23.530","Text":"These are more complex in a way than the cofactors."},{"Start":"02:23.530 ","End":"02:28.455","Text":"Examples of cofactors, we have Fe^2 plus,"},{"Start":"02:28.455 ","End":"02:29.970","Text":"magnesium 2 plus,"},{"Start":"02:29.970 ","End":"02:32.515","Text":"Mn^2 plus, Or Zn^2 plus."},{"Start":"02:32.515 ","End":"02:34.400","Text":"You see them here listed."},{"Start":"02:34.400 ","End":"02:38.030","Text":"These are the cofactors and these are"},{"Start":"02:38.030 ","End":"02:43.265","Text":"the enzymes that they serve as cofactors for their activity."},{"Start":"02:43.265 ","End":"02:46.660","Text":"Ni^2 plus is a cofactor for urease."},{"Start":"02:46.660 ","End":"02:52.880","Text":"Fe^2 plus or Fe^3 plus for cytochrome oxidase, catalase, peroxidase, etc."},{"Start":"02:52.880 ","End":"02:57.680","Text":"Examples of coenzymes are seen in this table."},{"Start":"02:57.680 ","End":"03:00.455","Text":"Again, you have the coenzyme biocytin."},{"Start":"03:00.455 ","End":"03:05.045","Text":"Since some coenzymes serve as transient carrier or specific atoms are functional groups,"},{"Start":"03:05.045 ","End":"03:07.940","Text":"biocytin you see CO_2 is an example of"},{"Start":"03:07.940 ","End":"03:11.150","Text":"a chemical group that is transferred by this coenzyme."},{"Start":"03:11.150 ","End":"03:16.430","Text":"You also have the dietary precursor mammals for this coenzyme."},{"Start":"03:16.430 ","End":"03:22.520","Text":"You have the coenzyme A that\u0027s associated with acyl groups and an entire list here."},{"Start":"03:22.520 ","End":"03:28.760","Text":"Some enzymes require both a coenzyme and one or more metal ions for activity."},{"Start":"03:28.760 ","End":"03:31.860","Text":"Again, you see part of the table of coenzymes,"},{"Start":"03:31.860 ","End":"03:35.150","Text":"these are the list of several examples of coenzymes,"},{"Start":"03:35.150 ","End":"03:42.065","Text":"and you have here the examples of cofactors and the enzymes that use them."},{"Start":"03:42.065 ","End":"03:45.950","Text":"Now a coenzyme or metal ion that is very tightly or even"},{"Start":"03:45.950 ","End":"03:50.000","Text":"covalently bound to the enzyme protein is called a prosthetic group."},{"Start":"03:50.000 ","End":"03:57.950","Text":"We mentioned prosthetic groups within the chapter on proteins and conjugated proteins."},{"Start":"03:57.950 ","End":"04:03.830","Text":"You have different prosthetic groups and the different classes based on the type of"},{"Start":"04:03.830 ","End":"04:06.770","Text":"a prosthetic group that we have and the examples that were"},{"Start":"04:06.770 ","End":"04:10.080","Text":"mentioned in a previous section."},{"Start":"04:10.080 ","End":"04:12.890","Text":"A complete catalytically active enzyme together with"},{"Start":"04:12.890 ","End":"04:17.915","Text":"its bound coenzyme and our metal ions is called a holoenzyme."},{"Start":"04:17.915 ","End":"04:19.910","Text":"Even though it is spelled differently,"},{"Start":"04:19.910 ","End":"04:26.555","Text":"it may help you to remember this term by the prefix holo, as in whole."},{"Start":"04:26.555 ","End":"04:30.185","Text":"It is a whole enzyme."},{"Start":"04:30.185 ","End":"04:37.040","Text":"The protein part of such an enzyme is called apoenzyme or apoprotein."},{"Start":"04:37.040 ","End":"04:39.140","Text":"To me actually the second term,"},{"Start":"04:39.140 ","End":"04:42.300","Text":"apoprotein is the more familiar as the one used more commonly,"},{"Start":"04:42.300 ","End":"04:45.320","Text":"but I want to make sure both terms are familiar to you since"},{"Start":"04:45.320 ","End":"04:48.500","Text":"they are in essence synonymous except"},{"Start":"04:48.500 ","End":"04:56.195","Text":"the apoprotein is more general and apoenzyme is an apoprotein that refers to an enzyme."},{"Start":"04:56.195 ","End":"05:01.040","Text":"Coenzymes act as transient carriers of specific functional groups."},{"Start":"05:01.040 ","End":"05:02.930","Text":"Most are derived from vitamins,"},{"Start":"05:02.930 ","End":"05:07.100","Text":"which are organic nutrients required in small amounts in the diet."},{"Start":"05:07.100 ","End":"05:10.820","Text":"We probably heard of this through dietary supplements or"},{"Start":"05:10.820 ","End":"05:14.510","Text":"things to eat and you see different vitamins listed here,"},{"Start":"05:14.510 ","End":"05:20.945","Text":"depicted here with associated dietary components that can provide these vitamins."},{"Start":"05:20.945 ","End":"05:23.600","Text":"You see different vegetables for vitamin A,"},{"Start":"05:23.600 ","End":"05:26.120","Text":"you see different proteins,"},{"Start":"05:26.120 ","End":"05:29.245","Text":"meats for the beef family, etc."},{"Start":"05:29.245 ","End":"05:32.315","Text":"We will expand on coenzymes as we come across them"},{"Start":"05:32.315 ","End":"05:35.420","Text":"in the metabolism pathways discovered in later lessons."},{"Start":"05:35.420 ","End":"05:41.078","Text":"Finally, some enzyme proteins are modified covalently by phosphorylation,"},{"Start":"05:41.078 ","End":"05:46.160","Text":"glycosylation, and other processes that happen in cells."},{"Start":"05:46.160 ","End":"05:52.010","Text":"Many of these alterations are involved in the regulation of enzyme activity,"},{"Start":"05:52.010 ","End":"05:57.815","Text":"meaning they can be associated with activating an enzyme or deactivating an enzyme."},{"Start":"05:57.815 ","End":"06:02.120","Text":"The active form of an enzyme could be associated with being phosphorylated,"},{"Start":"06:02.120 ","End":"06:04.565","Text":"glycosylated or the opposite."},{"Start":"06:04.565 ","End":"06:08.765","Text":"It can be deactivated by going through one of these processes."},{"Start":"06:08.765 ","End":"06:14.490","Text":"With this, we completed enzyme components section with an introduction to enzymes."},{"Start":"06:14.490 ","End":"06:17.330","Text":"We talked about enzyme components and general composition and"},{"Start":"06:17.330 ","End":"06:21.330","Text":"the contributory factors to enzyme catalytic activity."}],"ID":30095},{"Watched":false,"Name":"Exercise 3","Duration":"24s","ChapterTopicVideoID":28567,"CourseChapterTopicPlaylistID":286641,"HasSubtitles":true,"ThumbnailPath":null,"UploadDate":null,"DurationForVideoObject":null,"Description":null,"MetaTitle":null,"MetaDescription":null,"Canonical":null,"VideoComments":[],"Subtitles":[{"Start":"00:00.000 ","End":"00:04.365","Text":"We\u0027re within enzyme components and the topic"},{"Start":"00:04.365 ","End":"00:08.160","Text":"of introduction to enzyme within the chapter, enzymes."},{"Start":"00:08.160 ","End":"00:10.068","Text":"Almost all enzymes are proteins."},{"Start":"00:10.068 ","End":"00:12.030","Text":"What is the exception to this?"},{"Start":"00:12.030 ","End":"00:18.030","Text":"All enzymes are proteins with the exception of a small group of catalytic RNA molecules."},{"Start":"00:18.030 ","End":"00:20.340","Text":"These are called ribozymes,"},{"Start":"00:20.340 ","End":"00:23.860","Text":"which we briefly mentioned in a previous lesson."}],"ID":30096},{"Watched":false,"Name":"Exercise 4","Duration":"1m 5s","ChapterTopicVideoID":28568,"CourseChapterTopicPlaylistID":286641,"HasSubtitles":true,"ThumbnailPath":null,"UploadDate":null,"DurationForVideoObject":null,"Description":null,"MetaTitle":null,"MetaDescription":null,"Canonical":null,"VideoComments":[],"Subtitles":[{"Start":"00:00.000 ","End":"00:03.315","Text":"We have another exercise within enzyme components."},{"Start":"00:03.315 ","End":"00:07.350","Text":"A few factors were listed as significant to enzyme catalytic activity."},{"Start":"00:07.350 ","End":"00:08.620","Text":"Name a couple of these."},{"Start":"00:08.620 ","End":"00:12.255","Text":"Here are a few things we mentioned with regard to enzyme catalytic activity."},{"Start":"00:12.255 ","End":"00:17.190","Text":"Enzyme catalytic activity depends on the integrity of their native protein conformation."},{"Start":"00:17.190 ","End":"00:18.525","Text":"We talked about the structure."},{"Start":"00:18.525 ","End":"00:20.790","Text":"If an enzyme is denatured,"},{"Start":"00:20.790 ","End":"00:23.895","Text":"catalytic activity is usually lost."},{"Start":"00:23.895 ","End":"00:28.815","Text":"This also is correct if it\u0027s dissociated into its sub-units."},{"Start":"00:28.815 ","End":"00:32.400","Text":"If an enzyme is broken down into its component amino acids,"},{"Start":"00:32.400 ","End":"00:35.925","Text":"its catalytic activity is always destroyed."},{"Start":"00:35.925 ","End":"00:38.629","Text":"Thus, the primary, secondary,"},{"Start":"00:38.629 ","End":"00:41.585","Text":"tertiary and quaternary structures, basically saying,"},{"Start":"00:41.585 ","End":"00:48.560","Text":"the protein structure of enzymes is essential to its catalytic activity."},{"Start":"00:48.560 ","End":"00:53.360","Text":"Some enzymes require only their amino acid residues in order to be active,"},{"Start":"00:53.360 ","End":"00:58.745","Text":"while others require an additional chemical component called a cofactor or a coenzyme."},{"Start":"00:58.745 ","End":"01:05.160","Text":"Some enzymes require both a coenzyme and 1 or more metal ions for activity."}],"ID":30097},{"Watched":false,"Name":"Exercise 5","Duration":"1m 5s","ChapterTopicVideoID":28558,"CourseChapterTopicPlaylistID":286641,"HasSubtitles":true,"ThumbnailPath":null,"UploadDate":null,"DurationForVideoObject":null,"Description":null,"MetaTitle":null,"MetaDescription":null,"Canonical":null,"VideoComments":[],"Subtitles":[{"Start":"00:00.000 ","End":"00:03.960","Text":"We have another question within enzyme components."},{"Start":"00:03.960 ","End":"00:08.025","Text":"Define, explain, and give examples of a cofactor and a coenzyme."},{"Start":"00:08.025 ","End":"00:11.400","Text":"Some enzymes require an additional chemical component."},{"Start":"00:11.400 ","End":"00:13.875","Text":"This can be 1 of 2 things."},{"Start":"00:13.875 ","End":"00:19.530","Text":"One component that some enzymes rely on is called a co-factor,"},{"Start":"00:19.530 ","End":"00:23.445","Text":"which is either one or more inorganic ions."},{"Start":"00:23.445 ","End":"00:28.680","Text":"Another component that some enzymes require for catalytic function is"},{"Start":"00:28.680 ","End":"00:34.350","Text":"a complex organic or metalorganic molecule called a coenzyme."},{"Start":"00:34.350 ","End":"00:42.110","Text":"Examples of cofactors can be Fe^2 plus Mg^2 plus Mn^2 plus etc."},{"Start":"00:42.110 ","End":"00:48.590","Text":"You see a table here listing a few of these and the enzymes they are associated with."},{"Start":"00:48.590 ","End":"00:50.090","Text":"Don\u0027t need to memorize this."},{"Start":"00:50.090 ","End":"00:54.065","Text":"Examples of coenzymes are listed here."},{"Start":"00:54.065 ","End":"00:58.204","Text":"Biocytin, coenzyme A, lipoate, etc."},{"Start":"00:58.204 ","End":"01:00.830","Text":"Now there are cases of enzymes that require"},{"Start":"01:00.830 ","End":"01:06.210","Text":"both a coenzyme and one or more metal ions for activity."}],"ID":30098},{"Watched":false,"Name":"Exercise 6","Duration":"1m 21s","ChapterTopicVideoID":28559,"CourseChapterTopicPlaylistID":286641,"HasSubtitles":true,"ThumbnailPath":null,"UploadDate":null,"DurationForVideoObject":null,"Description":null,"MetaTitle":null,"MetaDescription":null,"Canonical":null,"VideoComments":[],"Subtitles":[{"Start":"00:00.000 ","End":"00:03.585","Text":"Welcome to another exercise within enzyme component."},{"Start":"00:03.585 ","End":"00:06.465","Text":"Define the following terms relating to enzymes."},{"Start":"00:06.465 ","End":"00:10.830","Text":"Prosthetic group, holoenzyme and apoprotein."},{"Start":"00:10.830 ","End":"00:15.930","Text":"A prosthetic group is a coenzyme or metal ion that is very"},{"Start":"00:15.930 ","End":"00:21.585","Text":"tightly or even covalently bound to the enzyme, to the protein."},{"Start":"00:21.585 ","End":"00:25.110","Text":"A holoenzyme is a complete catalytically active enzyme"},{"Start":"00:25.110 ","End":"00:29.295","Text":"together with its bound coenzyme and, or metal ions."},{"Start":"00:29.295 ","End":"00:31.215","Text":"Even though it is spelled differently,"},{"Start":"00:31.215 ","End":"00:35.715","Text":"I mentioned that one way to possibly remember this term is by the prefix holo,"},{"Start":"00:35.715 ","End":"00:39.315","Text":"associating it with the word whole."},{"Start":"00:39.315 ","End":"00:40.670","Text":"It is a whole,"},{"Start":"00:40.670 ","End":"00:44.255","Text":"an entire a complete enzyme."},{"Start":"00:44.255 ","End":"00:45.950","Text":"Holoenzyme."},{"Start":"00:45.950 ","End":"00:47.645","Text":"Whole enzyme."},{"Start":"00:47.645 ","End":"00:49.400","Text":"Apoprotein."},{"Start":"00:49.400 ","End":"00:53.495","Text":"This is also known as apoenzyme,"},{"Start":"00:53.495 ","End":"00:58.940","Text":"and it refers to the protein part of a holoenzyme of an enzyme complex because we"},{"Start":"00:58.940 ","End":"01:05.360","Text":"said that an entire enzyme complex can have cofactors,"},{"Start":"01:05.360 ","End":"01:13.280","Text":"coenzymes, but the apoprotein is the protein part of the entire"},{"Start":"01:13.280 ","End":"01:16.670","Text":"complete catalytically active enzyme together with"},{"Start":"01:16.670 ","End":"01:22.200","Text":"its bound coenzyme and, or metal ions."}],"ID":30099},{"Watched":false,"Name":"Exercise 7","Duration":"1m 30s","ChapterTopicVideoID":28560,"CourseChapterTopicPlaylistID":286641,"HasSubtitles":true,"ThumbnailPath":null,"UploadDate":null,"DurationForVideoObject":null,"Description":null,"MetaTitle":null,"MetaDescription":null,"Canonical":null,"VideoComments":[],"Subtitles":[{"Start":"00:00.000 ","End":"00:04.485","Text":"Further testing our knowledge of enzyme components."},{"Start":"00:04.485 ","End":"00:08.369","Text":"Fill in the blanks to complete the sentences with regard to coenzymes."},{"Start":"00:08.369 ","End":"00:11.880","Text":"1, coenzymes act as, blank,"},{"Start":"00:11.880 ","End":"00:16.170","Text":"carriers of specific, blank, groups."},{"Start":"00:16.170 ","End":"00:19.985","Text":"2, blank coenzymes are derived from, blank,"},{"Start":"00:19.985 ","End":"00:25.595","Text":"organic nutrients required in small amounts in the diet. Let\u0027s start with 1."},{"Start":"00:25.595 ","End":"00:33.325","Text":"Coenzymes act as what carriers of specific what groups?"},{"Start":"00:33.325 ","End":"00:39.320","Text":"Coenzymes act as transient carriers, meaning not consistent,"},{"Start":"00:39.320 ","End":"00:43.740","Text":"they\u0027re not bound to whatever they carry permanently,"},{"Start":"00:43.740 ","End":"00:46.965","Text":"it is something that is passing,"},{"Start":"00:46.965 ","End":"00:50.390","Text":"and the specific groups are functional groups."},{"Start":"00:50.390 ","End":"00:54.905","Text":"Coenzymes act as transient carriers of specific functional groups"},{"Start":"00:54.905 ","End":"01:00.160","Text":"that are important for enzymatic activity. Let\u0027s go into 2."},{"Start":"01:00.160 ","End":"01:02.755","Text":"Blank, coenzymes are derived from,"},{"Start":"01:02.755 ","End":"01:06.380","Text":"blank, organic nutrients required in small amounts in the diet."},{"Start":"01:06.380 ","End":"01:09.485","Text":"What did we mention that is required from the diet?"},{"Start":"01:09.485 ","End":"01:11.750","Text":"It\u0027s a term that we\u0027re all familiar with."},{"Start":"01:11.750 ","End":"01:17.630","Text":"Most coenzymes are derived from these organic nutrients and these organic nutrients,"},{"Start":"01:17.630 ","End":"01:19.220","Text":"if you remember the figure colorful,"},{"Start":"01:19.220 ","End":"01:22.280","Text":"we had different sources of these, are vitamins."},{"Start":"01:22.280 ","End":"01:25.054","Text":"Most coenzymes are derived from vitamins,"},{"Start":"01:25.054 ","End":"01:30.420","Text":"which are organic nutrients required in small amounts in the diet."}],"ID":30100},{"Watched":false,"Name":"Section 3 - Enzyme Classification","Duration":"7m 52s","ChapterTopicVideoID":28561,"CourseChapterTopicPlaylistID":286641,"HasSubtitles":true,"ThumbnailPath":null,"UploadDate":null,"DurationForVideoObject":null,"Description":null,"MetaTitle":null,"MetaDescription":null,"Canonical":null,"VideoComments":[],"Subtitles":[{"Start":"00:00.000 ","End":"00:03.240","Text":"We\u0027re within the introduction to enzymes,"},{"Start":"00:03.240 ","End":"00:05.610","Text":"and we\u0027re moving into enzyme classification,"},{"Start":"00:05.610 ","End":"00:09.270","Text":"where you will learn and be able by"},{"Start":"00:09.270 ","End":"00:16.470","Text":"the end of this section to explain how enzymes are classified and how enzymes are named."},{"Start":"00:16.470 ","End":"00:20.805","Text":"Enzymes are classified by the reactions they catalyze."},{"Start":"00:20.805 ","End":"00:26.070","Text":"Many enzymes have been named by adding the suffix, \"-ase\","},{"Start":"00:26.070 ","End":"00:32.865","Text":"peroxidase, transferase, polymerase, etc."},{"Start":"00:32.865 ","End":"00:38.790","Text":"By adding the suffix to the name of their substrate or to a word or phrase describing"},{"Start":"00:38.790 ","End":"00:45.065","Text":"their activity is the common way that enzymes have been named."},{"Start":"00:45.065 ","End":"00:46.940","Text":"In that regard."},{"Start":"00:46.940 ","End":"00:51.815","Text":"Urease catalyzes hydrolysis of urea."},{"Start":"00:51.815 ","End":"00:57.065","Text":"Urea combined with the suffix \"-ase\","},{"Start":"00:57.065 ","End":"01:02.060","Text":"urease and DNA polymerase,"},{"Start":"01:02.060 ","End":"01:09.845","Text":"catalyzes the polymerization of nucleotides to form DNA,"},{"Start":"01:09.845 ","End":"01:12.395","Text":"and here you have the suffix again."},{"Start":"01:12.395 ","End":"01:16.640","Text":"Other enzymes were named by their discovers for"},{"Start":"01:16.640 ","End":"01:21.065","Text":"a broad function before the specific reaction catalyzed was known."},{"Start":"01:21.065 ","End":"01:24.410","Text":"Because sometimes enzymes were isolated or recognized,"},{"Start":"01:24.410 ","End":"01:30.245","Text":"but the actual specific reaction wasn\u0027t yet identified."},{"Start":"01:30.245 ","End":"01:35.120","Text":"For example, an enzyme known to act in the digestion of foods was named"},{"Start":"01:35.120 ","End":"01:41.025","Text":"pepsin from the Greek term pepsis, which means digestion."},{"Start":"01:41.025 ","End":"01:49.865","Text":"Lysozyme was named for its ability to lyse bacterial cell walls. Lyse, lysozyme."},{"Start":"01:49.865 ","End":"01:51.800","Text":"Some enzymes, on the other hand,"},{"Start":"01:51.800 ","End":"01:53.885","Text":"were named for their source."},{"Start":"01:53.885 ","End":"01:59.539","Text":"For example, trypsin from the Greek tryein,\" to wear down.\""},{"Start":"01:59.539 ","End":"02:04.590","Text":"This was named in part from this term and"},{"Start":"02:04.590 ","End":"02:09.665","Text":"it was obtained by rubbing pancreatic tissue with glycerin."},{"Start":"02:09.665 ","End":"02:15.260","Text":"What resulted was wearing down of the pancreatic tissue."},{"Start":"02:15.260 ","End":"02:19.190","Text":"Therefore, the term wear down for"},{"Start":"02:19.190 ","End":"02:23.135","Text":"trypsin before it was completely isolated and recognized."},{"Start":"02:23.135 ","End":"02:26.510","Text":"Sometimes the same enzyme has 2 or more names,"},{"Start":"02:26.510 ","End":"02:29.191","Text":"or 2 different enzymes have the same name."},{"Start":"02:29.191 ","End":"02:35.510","Text":"Because of such ambiguities and the ever-increasing number of newly discovered enzymes,"},{"Start":"02:35.510 ","End":"02:38.390","Text":"biochemists by international agreement have"},{"Start":"02:38.390 ","End":"02:42.175","Text":"adopted a system of naming and classifying enzymes."},{"Start":"02:42.175 ","End":"02:46.240","Text":"This system divides enzymes into 6 classes,"},{"Start":"02:46.240 ","End":"02:50.710","Text":"each with subclasses based on the type of reaction catalyzed."},{"Start":"02:50.710 ","End":"02:59.035","Text":"What you see here is the table depicting these 6 classes that were established."},{"Start":"02:59.035 ","End":"03:02.500","Text":"Each enzyme is assigned a 4-part classification number,"},{"Start":"03:02.500 ","End":"03:04.870","Text":"an Enzyme Commission number,"},{"Start":"03:04.870 ","End":"03:07.720","Text":"and an EC number,"},{"Start":"03:07.720 ","End":"03:13.090","Text":"and a systematic name which identifies the reaction it catalyzes."},{"Start":"03:13.090 ","End":"03:16.390","Text":"As an example, the formal systematic name of the enzyme"},{"Start":"03:16.390 ","End":"03:20.170","Text":"catalyzing the reaction ATP plus D-glucose,"},{"Start":"03:20.170 ","End":"03:22.840","Text":"resulting in ADP plus glucose,"},{"Start":"03:22.840 ","End":"03:28.894","Text":"6-phosphate is ATP:D-Hexose 6-phosphotransferase."},{"Start":"03:28.894 ","End":"03:35.919","Text":"Again, ATP:D-Hexose 6-phosphotransferase."},{"Start":"03:35.919 ","End":"03:39.023","Text":"Its Enzyme Commission number,"},{"Start":"03:39.023 ","End":"03:45.290","Text":"the EC number, is 2.711."},{"Start":"03:45.290 ","End":"03:49.280","Text":"The first number 2 denotes the class name, transferase."},{"Start":"03:49.280 ","End":"03:51.170","Text":"Remember if we look here,"},{"Start":"03:51.170 ","End":"03:53.485","Text":"let\u0027s go through these 6 classes."},{"Start":"03:53.485 ","End":"03:56.960","Text":"The first class is oxidoreductases,"},{"Start":"03:56.960 ","End":"03:58.640","Text":"it\u0027s transfer of electron,"},{"Start":"03:58.640 ","End":"04:00.500","Text":"hydride ions, or H atoms."},{"Start":"04:00.500 ","End":"04:02.300","Text":"This is the type of reaction catalyzed."},{"Start":"04:02.300 ","End":"04:05.530","Text":"The first class is oxidoreductases,"},{"Start":"04:05.530 ","End":"04:08.675","Text":"oxidation, and reduction reactions."},{"Start":"04:08.675 ","End":"04:12.320","Text":"The second class is transferases, transfer,"},{"Start":"04:12.320 ","End":"04:16.175","Text":"groups transfer reactions, so they transfer reactions."},{"Start":"04:16.175 ","End":"04:18.425","Text":"Third group, hydrolases."},{"Start":"04:18.425 ","End":"04:19.875","Text":"Hydro, water."},{"Start":"04:19.875 ","End":"04:21.283","Text":"Hydrolysis reactions,"},{"Start":"04:21.283 ","End":"04:23.540","Text":"transfer of functional groups of water."},{"Start":"04:23.540 ","End":"04:25.560","Text":"Fourth group, lyases,"},{"Start":"04:25.560 ","End":"04:31.225","Text":"addition of group to double bonds or formation of double bonds by removal of groups."},{"Start":"04:31.225 ","End":"04:33.675","Text":"The fifth group, isomerases."},{"Start":"04:33.675 ","End":"04:38.870","Text":"Isomers, transfer of groups within molecules to yield isomeric forms. Remember isomers?"},{"Start":"04:38.870 ","End":"04:44.120","Text":"Different forms of the same basic molecule."},{"Start":"04:44.120 ","End":"04:46.175","Text":"The sixth group is ligases,"},{"Start":"04:46.175 ","End":"04:48.035","Text":"formation of C-C,"},{"Start":"04:48.035 ","End":"04:51.275","Text":"C-S or C-O, carbon-carbon carbon-sulfur,"},{"Start":"04:51.275 ","End":"04:53.840","Text":"carbon-oxygen and C-N, carbon-nitrogen,"},{"Start":"04:53.840 ","End":"04:59.550","Text":"bonds by condensation reaction coupled to ATP cleavage."},{"Start":"04:59.770 ","End":"05:05.075","Text":"When we look at our example here, number 2,"},{"Start":"05:05.075 ","End":"05:10.565","Text":"this stands for the second class, which is transferase."},{"Start":"05:10.565 ","End":"05:15.545","Text":"The second number, 7, denotes the subclass."},{"Start":"05:15.545 ","End":"05:18.770","Text":"This is phosphotransferase,"},{"Start":"05:18.770 ","End":"05:22.445","Text":"that way transfers phosphate groups."},{"Start":"05:22.445 ","End":"05:26.495","Text":"The third number indicates that it is"},{"Start":"05:26.495 ","End":"05:32.555","Text":"a phosphotransferase with a hydroxyl group as an acceptor."},{"Start":"05:32.555 ","End":"05:37.620","Text":"This 1 represents hydroxyl group as an acceptor."},{"Start":"05:37.620 ","End":"05:40.780","Text":"The fourth number, which is also 1,"},{"Start":"05:40.780 ","End":"05:46.355","Text":"means that it\u0027s a D-glucose as the phosphoryl group acceptor."},{"Start":"05:46.355 ","End":"05:52.420","Text":"This indicates D-glucose, basically glucose."},{"Start":"05:52.420 ","End":"05:57.420","Text":"The EC number of the ATP:D-Hexose"},{"Start":"05:57.420 ","End":"06:03.780","Text":"6-phosphotransferase is 2 to indicate transferase,"},{"Start":"06:03.780 ","End":"06:10.310","Text":"7 to indicate the phosphotransferase, the 1,"},{"Start":"06:10.310 ","End":"06:14.945","Text":"the third number indicates the hydroxyl group acceptor,"},{"Start":"06:14.945 ","End":"06:17.014","Text":"hydroxyl you have hexose,"},{"Start":"06:17.014 ","End":"06:19.940","Text":"and 1 is that it\u0027s D-glucose,"},{"Start":"06:19.940 ","End":"06:24.755","Text":"D for the D glucose hydroxyl group acceptor."},{"Start":"06:24.755 ","End":"06:28.880","Text":"This number is basically a short way,"},{"Start":"06:28.880 ","End":"06:34.805","Text":"a number representation of this entire name."},{"Start":"06:34.805 ","End":"06:40.330","Text":"This equals 2.7.1.1."},{"Start":"06:40.840 ","End":"06:49.010","Text":"Biochemists that specialize in these type of enzymatic naming and specializations"},{"Start":"06:49.010 ","End":"06:56.510","Text":"would be able to identify from this number that it is ATP:D-Hexose 6-phosphotransferase."},{"Start":"06:56.510 ","End":"07:04.040","Text":"Now, to summarize the entire introduction of enzymes,"},{"Start":"07:04.040 ","End":"07:07.460","Text":"we talked about the fact that life depends on the existence of"},{"Start":"07:07.460 ","End":"07:10.970","Text":"powerful and specific catalysts, the enzymes."},{"Start":"07:10.970 ","End":"07:14.734","Text":"Almost every biochemical reaction is catalyzed by an enzyme."},{"Start":"07:14.734 ","End":"07:18.050","Text":"With the exception of few catalytic RNAs,"},{"Start":"07:18.050 ","End":"07:21.505","Text":"all known enzymes are proteins."},{"Start":"07:21.505 ","End":"07:27.680","Text":"Many enzymes require non-protein coenzymes or cofactors for their catalytic function."},{"Start":"07:27.680 ","End":"07:32.405","Text":"Enzymes are classified according to the type of reaction they catalyze."},{"Start":"07:32.405 ","End":"07:36.055","Text":"All enzymes have formal EC numbers,"},{"Start":"07:36.055 ","End":"07:38.675","Text":"Enzyme Commission numbers,"},{"Start":"07:38.675 ","End":"07:41.935","Text":"and names, and most have trivial names."},{"Start":"07:41.935 ","End":"07:47.450","Text":"At this point, we completed enzyme classification and the introduction to enzymes."},{"Start":"07:47.450 ","End":"07:52.650","Text":"You should understand how enzymes are classified and how enzymes are named."}],"ID":30101},{"Watched":false,"Name":"Exercise 8","Duration":"1m 42s","ChapterTopicVideoID":28562,"CourseChapterTopicPlaylistID":286641,"HasSubtitles":true,"ThumbnailPath":null,"UploadDate":null,"DurationForVideoObject":null,"Description":null,"MetaTitle":null,"MetaDescription":null,"Canonical":null,"VideoComments":[],"Subtitles":[{"Start":"00:00.020 ","End":"00:03.900","Text":"We have an exercise with an enzyme classification."},{"Start":"00:03.900 ","End":"00:07.920","Text":"List 3 ways mentioned in the lesson for naming enzymes."},{"Start":"00:07.920 ","End":"00:12.480","Text":"Many enzymes are named by the addition of the suffix A-S-E to"},{"Start":"00:12.480 ","End":"00:16.875","Text":"the name of their substrate or to a word or phrase describing their activity."},{"Start":"00:16.875 ","End":"00:22.795","Text":"In that regard, urease catalyzes hydrolysis of urea."},{"Start":"00:22.795 ","End":"00:25.950","Text":"Urease, urea,"},{"Start":"00:25.950 ","End":"00:27.450","Text":"A-S-E is the suffix,"},{"Start":"00:27.450 ","End":"00:34.160","Text":"and DNA polymerase was given as an example because it catalyzes the polymerization,"},{"Start":"00:34.160 ","End":"00:36.280","Text":"polymer, polymerization,"},{"Start":"00:36.280 ","End":"00:39.405","Text":"polymer A-S-E, polymerase."},{"Start":"00:39.405 ","End":"00:45.140","Text":"DNA polymerase catalyzes the polymerization of nucleotides to form DNA."},{"Start":"00:45.140 ","End":"00:48.950","Text":"Some enzymes were named by their discoverers for a broad function"},{"Start":"00:48.950 ","End":"00:53.000","Text":"before the specific reaction catalyzed was known."},{"Start":"00:53.000 ","End":"00:57.710","Text":"For example, an enzyme known to act in the digestion of foods was named pepsin from"},{"Start":"00:57.710 ","End":"01:03.140","Text":"the Greek term Pepsis, which means digestion."},{"Start":"01:03.140 ","End":"01:07.430","Text":"Lysozyme was given as example for an enzyme"},{"Start":"01:07.430 ","End":"01:11.585","Text":"that was named after its ability to lyse bacterial cell walls."},{"Start":"01:11.585 ","End":"01:16.790","Text":"Lyse, lysozyme, and zyme, enzyme."},{"Start":"01:16.790 ","End":"01:24.605","Text":"The third way mentioned was some enzymes were named for their source, trypsin."},{"Start":"01:24.605 ","End":"01:28.340","Text":"This is named in part from the Greek term Tryein,"},{"Start":"01:28.340 ","End":"01:31.520","Text":"\"To wear down\" was obtained by rubbing pancreatic tissue with"},{"Start":"01:31.520 ","End":"01:35.225","Text":"glycerin wearing down the pancreatic tissue."},{"Start":"01:35.225 ","End":"01:37.890","Text":"Sometimes the same enzyme has 2 or more names,"},{"Start":"01:37.890 ","End":"01:41.940","Text":"or 2 different enzymes have the same name."}],"ID":30102},{"Watched":false,"Name":"Exercise 9","Duration":"2m 55s","ChapterTopicVideoID":28563,"CourseChapterTopicPlaylistID":286641,"HasSubtitles":true,"ThumbnailPath":null,"UploadDate":null,"DurationForVideoObject":null,"Description":null,"MetaTitle":null,"MetaDescription":null,"Canonical":null,"VideoComments":[],"Subtitles":[{"Start":"00:00.000 ","End":"00:04.665","Text":"We have another exercise with an enzyme classification."},{"Start":"00:04.665 ","End":"00:09.465","Text":"What is the system by which biochemists classify and name enzymes and give an example?"},{"Start":"00:09.465 ","End":"00:13.125","Text":"Enzymes are classified by the reactions they catalyze."},{"Start":"00:13.125 ","End":"00:15.510","Text":"Biochemists, by international agreement,"},{"Start":"00:15.510 ","End":"00:17.940","Text":"have adopted a system for naming and classifying"},{"Start":"00:17.940 ","End":"00:21.630","Text":"enzymes in which they are divided into 6 classes,"},{"Start":"00:21.630 ","End":"00:25.259","Text":"each with subclasses based on the type of reaction catalyzed."},{"Start":"00:25.259 ","End":"00:26.505","Text":"If you look at the table,"},{"Start":"00:26.505 ","End":"00:27.690","Text":"you have the 6 classes."},{"Start":"00:27.690 ","End":"00:29.595","Text":"The first one is oxidoreductases,"},{"Start":"00:29.595 ","End":"00:33.900","Text":"it transfers electrons, hydride ions or H atoms."},{"Start":"00:33.900 ","End":"00:36.855","Text":"This is from the term, oxidation, and reduction."},{"Start":"00:36.855 ","End":"00:40.205","Text":"Second group is transferases."},{"Start":"00:40.205 ","End":"00:42.530","Text":"These are groups that transfer reactions."},{"Start":"00:42.530 ","End":"00:45.320","Text":"You have hydrolysis, hydro from water,"},{"Start":"00:45.320 ","End":"00:48.425","Text":"hydrolysis reactions, transfer of functional groups to water."},{"Start":"00:48.425 ","End":"00:50.870","Text":"Lyases, addition of groups to double bond"},{"Start":"00:50.870 ","End":"00:53.450","Text":"or formation of double bonds by removal of groups."},{"Start":"00:53.450 ","End":"00:55.430","Text":"Then you have isomerases,"},{"Start":"00:55.430 ","End":"00:57.980","Text":"from the term isomers transfer groups within"},{"Start":"00:57.980 ","End":"01:01.210","Text":"molecules to yield isomeric forms of the same molecule."},{"Start":"01:01.210 ","End":"01:02.810","Text":"Last but not least,"},{"Start":"01:02.810 ","End":"01:06.140","Text":"we have ligases formation of C-C-C-S,"},{"Start":"01:06.140 ","End":"01:12.440","Text":"C-O and C-N bonds by condensation reaction coupled to ATP cleavage."},{"Start":"01:12.440 ","End":"01:17.690","Text":"Each enzyme is assigned a 4-part classification number,"},{"Start":"01:17.690 ","End":"01:20.990","Text":"the Enzyme Commission number, the EC number,"},{"Start":"01:20.990 ","End":"01:25.370","Text":"and a systematic name which identifies the reaction it catalyzes."},{"Start":"01:25.370 ","End":"01:31.290","Text":"As an example, the formal systematic name of the enzyme catalyzing the reaction ATP,"},{"Start":"01:31.290 ","End":"01:39.010","Text":"resulting in ADP plus D-glucose 6-phosphate is ATP, D-Hexose 6-phosphotransferase,"},{"Start":"01:39.010 ","End":"01:44.540","Text":"which indicates that it catalyzes the transfer of a phosphoryl group,"},{"Start":"01:44.540 ","End":"01:52.040","Text":"phosphotransferase, transfer of phosphoryl group from ATP to glucose."},{"Start":"01:52.040 ","End":"01:54.710","Text":"Its Enzyme Commission number,"},{"Start":"01:54.710 ","End":"01:58.435","Text":"its EC number is 2.7.1.1."},{"Start":"01:58.435 ","End":"02:00.715","Text":"The first number 2,"},{"Start":"02:00.715 ","End":"02:01.940","Text":"as mentioned in the lesson,"},{"Start":"02:01.940 ","End":"02:04.475","Text":"denotes the class name transferase."},{"Start":"02:04.475 ","End":"02:08.270","Text":"Because class 2 is transferases,"},{"Start":"02:08.270 ","End":"02:12.800","Text":"so 2 indicates transferase,"},{"Start":"02:12.800 ","End":"02:15.875","Text":"this is giving this association."},{"Start":"02:15.875 ","End":"02:18.950","Text":"The subclass 7,"},{"Start":"02:18.950 ","End":"02:22.220","Text":"the second number is phosphotransferase."},{"Start":"02:22.220 ","End":"02:28.775","Text":"7 indicates phosphotransferase because it\u0027s a transfer of the phosphoryl group."},{"Start":"02:28.775 ","End":"02:37.235","Text":"The third number, the 1 is a phosphotransferase with a hydroxyl group as an acceptor."},{"Start":"02:37.235 ","End":"02:39.410","Text":"This is what this indicates."},{"Start":"02:39.410 ","End":"02:45.170","Text":"The fourth number, an additional 1 indicates its D-glucose as"},{"Start":"02:45.170 ","End":"02:52.430","Text":"the phosphoryl group acceptor because it is a transfer from ATP to D-glucose."},{"Start":"02:52.430 ","End":"02:55.530","Text":"This is what this number indicates."}],"ID":30103}],"Thumbnail":null,"ID":286641},{"Name":"How Enzymes Work","TopicPlaylistFirstVideoID":0,"Duration":null,"Videos":[{"Watched":false,"Name":"How Enzymes Work","Duration":"4m 39s","ChapterTopicVideoID":28578,"CourseChapterTopicPlaylistID":286642,"HasSubtitles":true,"ThumbnailPath":"https://www.proprep.uk/Images/Videos_Thumbnails/28578.jpeg","UploadDate":"2022-03-06T11:50:20.6570000","DurationForVideoObject":"PT4M39S","Description":null,"MetaTitle":"How Enzymes Work: Video + Workbook | Proprep","MetaDescription":"Enzymes - How Enzymes Work. Watch the video made by an expert in the field. Download the workbook and maximize your learning.","Canonical":"https://www.proprep.uk/general-modules/all/biochemistry/enzymes/how-enzymes-work/vid30104","VideoComments":[],"Subtitles":[{"Start":"00:00.000 ","End":"00:04.920","Text":"Now we are going to talk about how enzymes work within the chapter on enzymes."},{"Start":"00:04.920 ","End":"00:06.566","Text":"By the end of this section,"},{"Start":"00:06.566 ","End":"00:08.280","Text":"you\u0027ll be able to understand"},{"Start":"00:08.280 ","End":"00:12.135","Text":"the essential characteristics enzymes have that contribute to life."},{"Start":"00:12.135 ","End":"00:16.544","Text":"The enzymatic catalysis of reactions is essential to living systems."},{"Start":"00:16.544 ","End":"00:19.065","Text":"Under biologically relevant conditions,"},{"Start":"00:19.065 ","End":"00:21.960","Text":"uncatalyzed reactions tend to be slow."},{"Start":"00:21.960 ","End":"00:27.690","Text":"Most biological molecules are quite stable in the neutral pH,"},{"Start":"00:27.690 ","End":"00:32.070","Text":"mild temperature, an aqueous environment inside cells."},{"Start":"00:32.070 ","End":"00:35.655","Text":"Furthermore, many common reactions in biochemistry,"},{"Start":"00:35.655 ","End":"00:44.210","Text":"entail chemical events that are unfavorable or unlikely in the cellular environment,"},{"Start":"00:44.210 ","End":"00:48.950","Text":"such as the transient formation of unstable charged intermediates,"},{"Start":"00:48.950 ","End":"00:51.110","Text":"are the collision of 2 or more molecules in"},{"Start":"00:51.110 ","End":"00:54.949","Text":"the precise orientation required for a reaction."},{"Start":"00:54.949 ","End":"00:59.075","Text":"Reactions required to digest food, send nerve signals,"},{"Start":"00:59.075 ","End":"01:01.085","Text":"or contract a muscle,"},{"Start":"01:01.085 ","End":"01:05.330","Text":"simply do not occur at a useful rate without catalysis."},{"Start":"01:05.330 ","End":"01:09.620","Text":"An enzyme circumvents these problems by providing"},{"Start":"01:09.620 ","End":"01:16.339","Text":"a specific environment within which a given reaction can occur more rapidly."},{"Start":"01:16.339 ","End":"01:19.168","Text":"If we have a reaction,"},{"Start":"01:19.168 ","End":"01:26.556","Text":"and it has to occur and overcome this barrier that we mentioned in previous sections,"},{"Start":"01:26.556 ","End":"01:31.610","Text":"this barrier, the enzyme lowers the energy"},{"Start":"01:31.610 ","End":"01:37.745","Text":"required to overcome this energy barrier and for the reaction to occur."},{"Start":"01:37.745 ","End":"01:41.240","Text":"Once it\u0027s lower, it\u0027s easier to overcome it."},{"Start":"01:41.240 ","End":"01:45.410","Text":"If you have a huge mountain that you need to get across,"},{"Start":"01:45.410 ","End":"01:47.225","Text":"that will be hard enough."},{"Start":"01:47.225 ","End":"01:53.000","Text":"If you have a mountain that somehow became smaller,"},{"Start":"01:53.000 ","End":"01:58.700","Text":"the altitude, the kilometers need across it just as an easier thing to surpass."},{"Start":"01:58.700 ","End":"02:00.020","Text":"That\u0027s the same idea."},{"Start":"02:00.020 ","End":"02:06.160","Text":"The enzyme minimizes, reduces this barrier,"},{"Start":"02:06.160 ","End":"02:09.410","Text":"this hill for the reaction to proceed."},{"Start":"02:09.410 ","End":"02:16.400","Text":"The distinguishing feature of an enzyme catalyzed reaction is that it takes place within"},{"Start":"02:16.400 ","End":"02:24.215","Text":"the confines of a pocket on the enzyme called the active site."},{"Start":"02:24.215 ","End":"02:28.280","Text":"You could see here we have an illustration of an enzyme and"},{"Start":"02:28.280 ","End":"02:32.795","Text":"the active site is in this specific illustration here."},{"Start":"02:32.795 ","End":"02:35.650","Text":"This is just to depict the idea,"},{"Start":"02:35.650 ","End":"02:38.960","Text":"but it\u0027s not actually the same in every enzyme,"},{"Start":"02:38.960 ","End":"02:41.600","Text":"and it\u0027s not necessarily in this shape."},{"Start":"02:41.600 ","End":"02:45.935","Text":"The molecule that is bound in the active site and"},{"Start":"02:45.935 ","End":"02:50.675","Text":"acted upon by the enzyme is called the substrate."},{"Start":"02:50.675 ","End":"02:52.730","Text":"Here you see the substrate,"},{"Start":"02:52.730 ","End":"02:57.290","Text":"the substrate on which the enzyme takes action."},{"Start":"02:57.290 ","End":"03:02.945","Text":"The substrate is what fits into the active site of the enzyme."},{"Start":"03:02.945 ","End":"03:07.310","Text":"The surface of the active site is lined with amino acid residues with"},{"Start":"03:07.310 ","End":"03:12.665","Text":"substituent groups that bind the substrate and catalyze its chemical transformation."},{"Start":"03:12.665 ","End":"03:19.770","Text":"These amino acid residues allow with their substituent groups to bind the substrate."},{"Start":"03:19.770 ","End":"03:26.360","Text":"There\u0027s some interaction, some bonding that allows the catalysis and"},{"Start":"03:26.360 ","End":"03:33.395","Text":"the chemical transformation that results in the desired progress of the reaction."},{"Start":"03:33.395 ","End":"03:37.250","Text":"Often the active site encloses a substrate,"},{"Start":"03:37.250 ","End":"03:40.070","Text":"sequestering it completely from solution."},{"Start":"03:40.070 ","End":"03:43.370","Text":"Now, here we\u0027re not seeing that it\u0027s sequestered completely."},{"Start":"03:43.370 ","End":"03:45.395","Text":"Here you still see a surface open,"},{"Start":"03:45.395 ","End":"03:48.170","Text":"but there are cases where the enzyme will sequester"},{"Start":"03:48.170 ","End":"03:51.950","Text":"completely so it will fold in and basically swallow"},{"Start":"03:51.950 ","End":"03:59.160","Text":"it inside so that the enzyme now has completely sequestered,"},{"Start":"03:59.160 ","End":"04:04.775","Text":"engulf the substrate and therefore sequestering it from solution."},{"Start":"04:04.775 ","End":"04:07.430","Text":"The enzyme substrate complex,"},{"Start":"04:07.430 ","End":"04:12.695","Text":"whose existence was first proposed by Charles Adolphe Wurtz in 1880,"},{"Start":"04:12.695 ","End":"04:16.175","Text":"is central to the action of enzymes."},{"Start":"04:16.175 ","End":"04:17.810","Text":"It is also the starting point for"},{"Start":"04:17.810 ","End":"04:20.780","Text":"mathematical treatments that define the kinetic behavior of"},{"Start":"04:20.780 ","End":"04:25.820","Text":"enzyme catalyzed reactions and for theoretical descriptions of enzyme mechanisms,"},{"Start":"04:25.820 ","End":"04:28.490","Text":"which I will not expand on here."},{"Start":"04:28.490 ","End":"04:30.500","Text":"That is the big picture,"},{"Start":"04:30.500 ","End":"04:32.915","Text":"the zoom out of how enzymes work."},{"Start":"04:32.915 ","End":"04:35.450","Text":"By now, you should have a grasp of"},{"Start":"04:35.450 ","End":"04:39.540","Text":"the essential characteristics enzymes have that contribute to life."}],"ID":30104},{"Watched":false,"Name":"Exercise 1","Duration":"1m 55s","ChapterTopicVideoID":28580,"CourseChapterTopicPlaylistID":286642,"HasSubtitles":true,"ThumbnailPath":null,"UploadDate":null,"DurationForVideoObject":null,"Description":null,"MetaTitle":null,"MetaDescription":null,"Canonical":null,"VideoComments":[],"Subtitles":[{"Start":"00:00.000 ","End":"00:04.305","Text":"We are within the topic of how enzymes work."},{"Start":"00:04.305 ","End":"00:07.035","Text":"This is our first exercise."},{"Start":"00:07.035 ","End":"00:10.227","Text":"Many reactions can take place in the absence of enzymes,"},{"Start":"00:10.227 ","End":"00:15.000","Text":"yet enzymes\u0027 presence play a crucial role in these occurring within living organisms."},{"Start":"00:15.000 ","End":"00:18.540","Text":"Explain this concept as presented in the lesson."},{"Start":"00:18.540 ","End":"00:23.130","Text":"In essence, the enzymatic catalysis of reactions is essential to"},{"Start":"00:23.130 ","End":"00:28.485","Text":"living systems by increasing the rate and/or probability of occurring."},{"Start":"00:28.485 ","End":"00:30.375","Text":"As mentioned in the lesson,"},{"Start":"00:30.375 ","End":"00:32.520","Text":"under biologically relevant conditions,"},{"Start":"00:32.520 ","End":"00:34.080","Text":"reactions tend to be slow."},{"Start":"00:34.080 ","End":"00:37.444","Text":"Most biological molecules are quite stable in the neutral pH,"},{"Start":"00:37.444 ","End":"00:41.655","Text":"mild temperature, and aqueous environment that is found inside cells."},{"Start":"00:41.655 ","End":"00:44.960","Text":"Furthermore, many common reactions in biochemistry entail"},{"Start":"00:44.960 ","End":"00:49.355","Text":"chemical events that are unfavorable or unlikely in the cellular environment,"},{"Start":"00:49.355 ","End":"00:51.920","Text":"such as the collision of 2 or more molecules in"},{"Start":"00:51.920 ","End":"00:56.180","Text":"the precise orientation required for reaction."},{"Start":"00:56.180 ","End":"01:01.535","Text":"Reactions required to digest food, send nerve signals,"},{"Start":"01:01.535 ","End":"01:07.400","Text":"or contract the muscle simply do not occur at a useful rate without catalysis."},{"Start":"01:07.400 ","End":"01:11.270","Text":"An enzyme circumvents these problems by providing"},{"Start":"01:11.270 ","End":"01:17.250","Text":"a specific environment within which a given reaction can occur more rapidly."}],"ID":30105},{"Watched":false,"Name":"Exercise 2","Duration":"1m 17s","ChapterTopicVideoID":28579,"CourseChapterTopicPlaylistID":286642,"HasSubtitles":true,"ThumbnailPath":null,"UploadDate":null,"DurationForVideoObject":null,"Description":null,"MetaTitle":null,"MetaDescription":null,"Canonical":null,"VideoComments":[],"Subtitles":[{"Start":"00:00.000 ","End":"00:04.455","Text":"Welcome back to another exercise within the section of how enzymes work."},{"Start":"00:04.455 ","End":"00:07.470","Text":"Define the active site and the substrate and how"},{"Start":"00:07.470 ","End":"00:10.410","Text":"these play a role in an enzyme-catalyzed reaction."},{"Start":"00:10.410 ","End":"00:14.850","Text":"The distinguishing feature of an enzyme-catalyzed reaction is that it takes place"},{"Start":"00:14.850 ","End":"00:19.890","Text":"within the confines of a pocket on the enzyme called the active site."},{"Start":"00:19.890 ","End":"00:21.900","Text":"Within the enzyme,"},{"Start":"00:21.900 ","End":"00:24.975","Text":"the little pocket or the area where"},{"Start":"00:24.975 ","End":"00:29.085","Text":"the enzyme-catalyzed reaction takes place is called the active site."},{"Start":"00:29.085 ","End":"00:31.440","Text":"The molecule that is bound in the active site"},{"Start":"00:31.440 ","End":"00:34.920","Text":"and acted upon by the enzyme is called the substrate."},{"Start":"00:34.920 ","End":"00:36.725","Text":"You have the substrate,"},{"Start":"00:36.725 ","End":"00:38.525","Text":"whatever it may be,"},{"Start":"00:38.525 ","End":"00:41.165","Text":"it comes in the enzyme,"},{"Start":"00:41.165 ","End":"00:45.140","Text":"takes it in, places it in the active site."},{"Start":"00:45.140 ","End":"00:46.310","Text":"This is where they bind,"},{"Start":"00:46.310 ","End":"00:47.600","Text":"this is where they interact,"},{"Start":"00:47.600 ","End":"00:50.345","Text":"and then you see the enzyme substrate complex here"},{"Start":"00:50.345 ","End":"00:53.680","Text":"where the substrate has fit in the active site,"},{"Start":"00:53.680 ","End":"00:56.780","Text":"and then this allows for the process to"},{"Start":"00:56.780 ","End":"01:00.439","Text":"occur where it results in the product of the reaction."},{"Start":"01:00.439 ","End":"01:07.265","Text":"The substrate is the actual molecule that the enzyme acts on."},{"Start":"01:07.265 ","End":"01:11.580","Text":"The reaction occurs and affects this substrate,"},{"Start":"01:11.580 ","End":"01:18.170","Text":"and the substrate fits into the pocket of the enzyme that is called the active site."},{"Start":"01:18.170 ","End":"01:22.490","Text":"The surface of the enzyme\u0027s active site is lined with amino acid residues with"},{"Start":"01:22.490 ","End":"01:27.815","Text":"substituent groups that bind the substrate and catalyze its chemical transformation."},{"Start":"01:27.815 ","End":"01:29.810","Text":"These amino acid residues and"},{"Start":"01:29.810 ","End":"01:33.830","Text":"their substituent groups are what allow the binding and the interaction between"},{"Start":"01:33.830 ","End":"01:36.740","Text":"the substrate and the enzyme and allows"},{"Start":"01:36.740 ","End":"01:40.205","Text":"whatever chemical transformation needs to take place."},{"Start":"01:40.205 ","End":"01:43.790","Text":"Frequently, the active site encloses the substrate,"},{"Start":"01:43.790 ","End":"01:46.385","Text":"sequestering it completely from solution,"},{"Start":"01:46.385 ","End":"01:49.700","Text":"providing an environment that is conducive to reaction"},{"Start":"01:49.700 ","End":"01:54.000","Text":"taking place in the enzyme-substrate complex."}],"ID":30106},{"Watched":false,"Name":"Reaction Rates - Part 1","Duration":"13m 32s","ChapterTopicVideoID":28581,"CourseChapterTopicPlaylistID":286642,"HasSubtitles":true,"ThumbnailPath":null,"UploadDate":null,"DurationForVideoObject":null,"Description":null,"MetaTitle":null,"MetaDescription":null,"Canonical":null,"VideoComments":[],"Subtitles":[{"Start":"00:00.000 ","End":"00:02.040","Text":"As we explain how enzymes work,"},{"Start":"00:02.040 ","End":"00:05.925","Text":"we talked about the fact that it catalyzes the reaction."},{"Start":"00:05.925 ","End":"00:09.750","Text":"One very important concept is the reaction rate."},{"Start":"00:09.750 ","End":"00:13.410","Text":"By the end of this section, you\u0027ll be able to understand enzymes and reaction rate,"},{"Start":"00:13.410 ","End":"00:17.640","Text":"explain the role of an enzyme as a catalyst and relate the term ground state,"},{"Start":"00:17.640 ","End":"00:19.830","Text":"transition state and activation energy."},{"Start":"00:19.830 ","End":"00:24.765","Text":"Let\u0027s begin. We will start with Part 1 of this section."},{"Start":"00:24.765 ","End":"00:28.200","Text":"Enzymes affect reaction rates, not equilibria."},{"Start":"00:28.200 ","End":"00:32.655","Text":"This is a very important thing to understand and remember,"},{"Start":"00:32.655 ","End":"00:35.810","Text":"enzymes affect the reaction rates,"},{"Start":"00:35.810 ","End":"00:39.065","Text":"not the actual equilibria of the reaction."},{"Start":"00:39.065 ","End":"00:43.700","Text":"A simple enzymatic reaction might be written as such,"},{"Start":"00:43.700 ","End":"00:45.715","Text":"E plus S,"},{"Start":"00:45.715 ","End":"00:49.670","Text":"you have an equilibrium between ES and then"},{"Start":"00:49.670 ","End":"00:55.550","Text":"EP and resulting in E plus P. This is like saying,"},{"Start":"00:55.550 ","End":"01:00.815","Text":"we mentioned the term substrate and product."},{"Start":"01:00.815 ","End":"01:05.435","Text":"Also from previous sections."},{"Start":"01:05.435 ","End":"01:08.555","Text":"Like saying reactant, well,"},{"Start":"01:08.555 ","End":"01:11.795","Text":"this would be enzyme plus substrate,"},{"Start":"01:11.795 ","End":"01:14.420","Text":"but this is like saying reactants and products."},{"Start":"01:14.420 ","End":"01:17.180","Text":"The E here stands for enzyme."},{"Start":"01:17.180 ","End":"01:20.050","Text":"It\u0027s the enzyme and the substrate, they interact,"},{"Start":"01:20.050 ","End":"01:24.110","Text":"and then you have an enzyme-substrate complex."},{"Start":"01:24.110 ","End":"01:27.360","Text":"If you see here, you have the enzyme and the substrate,"},{"Start":"01:27.360 ","End":"01:30.560","Text":"we mentioned these previously, enzyme and substrate."},{"Start":"01:30.560 ","End":"01:34.040","Text":"They form an enzyme substrate complex."},{"Start":"01:34.040 ","End":"01:36.050","Text":"Now, you see the double arrow."},{"Start":"01:36.050 ","End":"01:37.865","Text":"These can go back and forth."},{"Start":"01:37.865 ","End":"01:45.574","Text":"The enzyme substrate complex then results in some chemical process,"},{"Start":"01:45.574 ","End":"01:48.080","Text":"some reaction that then it becomes"},{"Start":"01:48.080 ","End":"01:51.965","Text":"the enzyme products complex or the enzyme product complex."},{"Start":"01:51.965 ","End":"01:54.725","Text":"That\u0027s what the EP stands for."},{"Start":"01:54.725 ","End":"01:58.620","Text":"Enzyme substrate complex, enzyme product complex."},{"Start":"01:58.620 ","End":"02:02.645","Text":"Then you have the enzyme plus product,"},{"Start":"02:02.645 ","End":"02:05.570","Text":"because now these are separate entities."},{"Start":"02:05.570 ","End":"02:08.675","Text":"Now you have enzyme plus the product."},{"Start":"02:08.675 ","End":"02:12.020","Text":"It\u0027s like saying a previous chemical reactions"},{"Start":"02:12.020 ","End":"02:15.095","Text":"where we talked about equilibria and reaction rates."},{"Start":"02:15.095 ","End":"02:17.705","Text":"We had talked about reactants."},{"Start":"02:17.705 ","End":"02:21.590","Text":"Even if we\u0027re talking about in equilibrium reaction,"},{"Start":"02:21.590 ","End":"02:25.585","Text":"reactants and products or product."},{"Start":"02:25.585 ","End":"02:30.230","Text":"Here we\u0027re just referring to enzyme and substrate."},{"Start":"02:30.230 ","End":"02:32.120","Text":"These are the reactants and then you have"},{"Start":"02:32.120 ","End":"02:36.230","Text":"two intermediate states where there are these complexes,"},{"Start":"02:36.230 ","End":"02:38.930","Text":"the enzyme substrate complex and the enzyme product complex."},{"Start":"02:38.930 ","End":"02:40.730","Text":"Then you have the products."},{"Start":"02:40.730 ","End":"02:43.370","Text":"It\u0027s actually the enzyme and the product."},{"Start":"02:43.370 ","End":"02:48.095","Text":"This is where E, S and P represent the enzyme substrate and product"},{"Start":"02:48.095 ","End":"02:53.330","Text":"ES and EP are transient complexes of the enzyme with the substrate and with the product."},{"Start":"02:53.330 ","End":"02:57.350","Text":"To understand catalysis, we must first appreciate"},{"Start":"02:57.350 ","End":"03:01.610","Text":"the important distinction between reaction equilibria and reaction rates."},{"Start":"03:01.610 ","End":"03:05.750","Text":"Again, E, S and P represent the enzyme substrate and product,"},{"Start":"03:05.750 ","End":"03:11.120","Text":"ES and EP are transient complexes of the enzyme with the substrate and with the product."},{"Start":"03:11.120 ","End":"03:13.070","Text":"Now to understand catalysis,"},{"Start":"03:13.070 ","End":"03:15.620","Text":"we must first appreciate the important distinction between"},{"Start":"03:15.620 ","End":"03:20.380","Text":"reaction equilibria and reaction rates."},{"Start":"03:20.380 ","End":"03:24.769","Text":"The function of a catalyst is to increase the rate of reaction."},{"Start":"03:24.769 ","End":"03:28.895","Text":"Catalysts do not affect reaction equilibria."},{"Start":"03:28.895 ","End":"03:34.085","Text":"Any reactions such as substrate to product,"},{"Start":"03:34.085 ","End":"03:38.660","Text":"can be described by a reaction coordinate diagram."},{"Start":"03:38.660 ","End":"03:44.060","Text":"Now, the energy changes during the reaction."},{"Start":"03:44.060 ","End":"03:47.164","Text":"As discussed in a previous chapter,"},{"Start":"03:47.164 ","End":"03:51.710","Text":"energy in biological systems is described in terms of free energy,"},{"Start":"03:51.710 ","End":"03:56.090","Text":"G. In the coordinate diagram that is"},{"Start":"03:56.090 ","End":"04:03.305","Text":"used to depict and describe such reaction between substrate and product."},{"Start":"04:03.305 ","End":"04:07.250","Text":"The free energy of the system is plotted against the progress of"},{"Start":"04:07.250 ","End":"04:11.055","Text":"the reaction in the reaction coordinate."},{"Start":"04:11.055 ","End":"04:17.210","Text":"The starting point for the forward or the reverse reaction is called the ground state."},{"Start":"04:17.210 ","End":"04:18.830","Text":"In chemistry and physics,"},{"Start":"04:18.830 ","End":"04:20.210","Text":"the ground state is defined as"},{"Start":"04:20.210 ","End":"04:24.350","Text":"the lowest allowed energy state of an atom, molecule, or ion."},{"Start":"04:24.350 ","End":"04:28.295","Text":"In other words, the ground state represents the most stable configuration."},{"Start":"04:28.295 ","End":"04:30.880","Text":"If there\u0027s more than one possible ground state,"},{"Start":"04:30.880 ","End":"04:33.755","Text":"degenerate states are said to exist."},{"Start":"04:33.755 ","End":"04:36.800","Text":"Even though the species may possess some level of energy,"},{"Start":"04:36.800 ","End":"04:41.780","Text":"the ground state is considered to have 0 point energy in comparison to other states."},{"Start":"04:41.780 ","End":"04:44.300","Text":"If a species has energy greater than the ground state,"},{"Start":"04:44.300 ","End":"04:46.790","Text":"it is said to be in an excited state."},{"Start":"04:46.790 ","End":"04:51.980","Text":"The ground state, even if the molecule has some level of energy,"},{"Start":"04:51.980 ","End":"04:57.770","Text":"is considered to have 0 point energy so that everything"},{"Start":"04:57.770 ","End":"05:04.760","Text":"from there is going up or in the rear and different case down."},{"Start":"05:04.760 ","End":"05:08.644","Text":"Now, when a species has energy,"},{"Start":"05:08.644 ","End":"05:14.100","Text":"it is then considered in the excited state."},{"Start":"05:14.140 ","End":"05:18.650","Text":"Electrons provide a good example of ground and excited states."},{"Start":"05:18.650 ","End":"05:20.615","Text":"If an electron absorbs energy,"},{"Start":"05:20.615 ","End":"05:25.505","Text":"it may jump to an excited state and at some point,"},{"Start":"05:25.505 ","End":"05:28.685","Text":"the electron will return to the ground state,"},{"Start":"05:28.685 ","End":"05:32.250","Text":"typically giving off a photon in the process."},{"Start":"05:32.250 ","End":"05:36.875","Text":"Looking at this figure that we had seen previously in a previous chapter,"},{"Start":"05:36.875 ","End":"05:40.280","Text":"this can be considered the coordinate diagram and"},{"Start":"05:40.280 ","End":"05:43.670","Text":"the free energy of the system would be plotted."},{"Start":"05:43.670 ","End":"05:46.520","Text":"Here we have it, it\u0027s written as potential energy."},{"Start":"05:46.520 ","End":"05:53.180","Text":"But same idea plotted against the progress of the reaction, the reaction coordinate."},{"Start":"05:53.180 ","End":"05:56.030","Text":"Now the starting point for the reaction is the ground-state."},{"Start":"05:56.030 ","End":"05:59.885","Text":"See here it\u0027s considered to have the 0 point energy."},{"Start":"05:59.885 ","End":"06:05.160","Text":"Using that idea of the electron that absorbs energy,"},{"Start":"06:05.160 ","End":"06:09.095","Text":"and is activated, it is in activated state."},{"Start":"06:09.095 ","End":"06:12.500","Text":"It is then considered an excited state."},{"Start":"06:12.500 ","End":"06:17.900","Text":"Now we will go over a similar figure that explains this later on in the lesson,"},{"Start":"06:17.900 ","End":"06:22.450","Text":"but I just wanted to reintroduce this figure and the idea so you can visualize it."},{"Start":"06:22.450 ","End":"06:26.180","Text":"To describe the free energy changes for reactions,"},{"Start":"06:26.180 ","End":"06:30.665","Text":"we use what chemists defined as a standard set of conditions."},{"Start":"06:30.665 ","End":"06:34.620","Text":"This means temperature of 298 Kelvin,"},{"Start":"06:34.620 ","End":"06:40.220","Text":"partial pressure of each gas is 1 atmosphere or 101.3 kilo Pascals."},{"Start":"06:40.220 ","End":"06:42.800","Text":"This is the same thing, a different way of measuring,"},{"Start":"06:42.800 ","End":"06:47.385","Text":"just like we have Fahrenheit and Celsius is a different measure of temperature."},{"Start":"06:47.385 ","End":"06:49.230","Text":"Concentration of each solute,"},{"Start":"06:49.230 ","End":"06:57.860","Text":"1 molar and the free energy change for this reacting system as Delta G,"},{"Start":"06:57.860 ","End":"07:00.575","Text":"the standard free energy change."},{"Start":"07:00.575 ","End":"07:06.590","Text":"Just as an FYI because biochemical systems commonly involved H plus,"},{"Start":"07:06.590 ","End":"07:09.800","Text":"hydrogen plus a proton concentrations far below"},{"Start":"07:09.800 ","End":"07:16.250","Text":"1 molar biochemists define a biochemical standard free energy change of a Delta G,"},{"Start":"07:16.250 ","End":"07:21.485","Text":"the standard free energy change at the pH of 7,"},{"Start":"07:21.485 ","End":"07:23.645","Text":"just as an FYI,"},{"Start":"07:23.645 ","End":"07:25.430","Text":"since this may come up."},{"Start":"07:25.430 ","End":"07:28.090","Text":"The equilibrium between S and P"},{"Start":"07:28.090 ","End":"07:31.865","Text":"reflects the difference in the free energies of their ground states."},{"Start":"07:31.865 ","End":"07:33.875","Text":"Looking at this figure here,"},{"Start":"07:33.875 ","End":"07:40.970","Text":"the free energy of the ground state of P is lower than that of"},{"Start":"07:40.970 ","End":"07:50.220","Text":"S. Delta G for the reaction is negative and the equilibrium favors P, the product."},{"Start":"07:50.220 ","End":"07:51.450","Text":"Let\u0027s re-emphasize."},{"Start":"07:51.450 ","End":"07:56.570","Text":"The position and direction of the equilibrium are not affected by any catalyst."},{"Start":"07:56.570 ","End":"08:02.750","Text":"A favorable equilibrium does not mean that the S goes towards the P,"},{"Start":"08:02.750 ","End":"08:06.740","Text":"the substrate towards the product with an arrow that\u0027s unidirectional,"},{"Start":"08:06.740 ","End":"08:11.795","Text":"that the S to P conversion will occur at a detectable rate."},{"Start":"08:11.795 ","End":"08:17.770","Text":"Again, favorable equilibrium does not mean that the S converts to P,"},{"Start":"08:17.770 ","End":"08:19.815","Text":"at a detectable rate."},{"Start":"08:19.815 ","End":"08:24.065","Text":"The rate of reaction is dependent on an entirely different parameter."},{"Start":"08:24.065 ","End":"08:28.670","Text":"There is an energy barrier between the substrate and the product,"},{"Start":"08:28.670 ","End":"08:32.225","Text":"between S and P. What does this mean?"},{"Start":"08:32.225 ","End":"08:33.920","Text":"Looking at this figure,"},{"Start":"08:33.920 ","End":"08:35.990","Text":"you have this barrier here."},{"Start":"08:35.990 ","End":"08:38.360","Text":"This thing that you need to overcome,"},{"Start":"08:38.360 ","End":"08:42.680","Text":"that needs to be overcome in order for the reaction to move forward."},{"Start":"08:42.680 ","End":"08:44.870","Text":"Let\u0027s looking at this figure."},{"Start":"08:44.870 ","End":"08:48.260","Text":"This is another figure depicting the same idea."},{"Start":"08:48.260 ","End":"08:52.280","Text":"You have the same hill, the transition state,"},{"Start":"08:52.280 ","End":"08:56.705","Text":"the Delta G of substrate to product, seen here."},{"Start":"08:56.705 ","End":"08:58.925","Text":"You have this is when it\u0027s uncatalyzed."},{"Start":"08:58.925 ","End":"09:00.890","Text":"This is when it\u0027s catalyzed,"},{"Start":"09:00.890 ","End":"09:02.960","Text":"the hill is smaller."},{"Start":"09:02.960 ","End":"09:09.605","Text":"Just a different illustration depicting the same idea with different emphasis."},{"Start":"09:09.605 ","End":"09:11.465","Text":"Let\u0027s move forward from this."},{"Start":"09:11.465 ","End":"09:15.590","Text":"The energy required for alignment of reacting groups,"},{"Start":"09:15.590 ","End":"09:19.040","Text":"formation of transient, unstable charges,"},{"Start":"09:19.040 ","End":"09:22.820","Text":"bond rearrangements and other transformations required for the reaction to"},{"Start":"09:22.820 ","End":"09:27.770","Text":"proceed in either direction is this energy barrier."},{"Start":"09:27.770 ","End":"09:31.790","Text":"This is illustrated by the energy hill as seen here."},{"Start":"09:31.790 ","End":"09:33.380","Text":"This is the energy hill."},{"Start":"09:33.380 ","End":"09:35.120","Text":"For a reaction to proceed,"},{"Start":"09:35.120 ","End":"09:38.030","Text":"the molecules must overcome this barrier and therefore"},{"Start":"09:38.030 ","End":"09:41.240","Text":"must be raised to a higher energy level,"},{"Start":"09:41.240 ","End":"09:45.080","Text":"a higher G in order for the reaction to completion."},{"Start":"09:45.080 ","End":"09:47.030","Text":"At the top of the energy hill,"},{"Start":"09:47.030 ","End":"09:51.560","Text":"the above-mentioned energy barrier is a point at which decay to"},{"Start":"09:51.560 ","End":"09:56.600","Text":"the substrate or product is equally probable."},{"Start":"09:56.600 ","End":"09:59.320","Text":"It is downhill either way."},{"Start":"09:59.320 ","End":"10:01.640","Text":"At the top of this hill,"},{"Start":"10:01.640 ","End":"10:07.995","Text":"either going down to the product P or to S is equally probable."},{"Start":"10:07.995 ","End":"10:10.475","Text":"Just to explain what this figure is what we\u0027re seeing."},{"Start":"10:10.475 ","End":"10:12.290","Text":"This is a reaction coordinate diagram"},{"Start":"10:12.290 ","End":"10:17.345","Text":"comparing enzyme catalyzed reaction and uncatalyzed reactions."},{"Start":"10:17.345 ","End":"10:23.730","Text":"The reaction S to P. The ES and EP intermediates that we mentioned before,"},{"Start":"10:23.730 ","End":"10:26.540","Text":"enzyme substrate and enzyme product intermediates"},{"Start":"10:26.540 ","End":"10:29.510","Text":"occupy minima in the energy progress curve,"},{"Start":"10:29.510 ","End":"10:30.950","Text":"the enzyme catalyzed reactions."},{"Start":"10:30.950 ","End":"10:33.305","Text":"This is a smaller hill,"},{"Start":"10:33.305 ","End":"10:36.530","Text":"this is what makes the catalysis."},{"Start":"10:36.530 ","End":"10:39.905","Text":"This is what makes enzyme-catalyzed reaction possible."},{"Start":"10:39.905 ","End":"10:46.400","Text":"The terms Delta G uncat and Delta G cat correspond to"},{"Start":"10:46.400 ","End":"10:49.370","Text":"the activation energy for the uncatalyzed reaction and"},{"Start":"10:49.370 ","End":"10:53.840","Text":"the overall activation energy for the catalyzed reaction respectively."},{"Start":"10:53.840 ","End":"11:00.675","Text":"The activation energy is lower when the enzyme catalyzes the reaction."},{"Start":"11:00.675 ","End":"11:05.100","Text":"The activation energy that needs to be overcome in order to result in product,"},{"Start":"11:05.100 ","End":"11:08.750","Text":"this hill is a lot lower with free energy,"},{"Start":"11:08.750 ","End":"11:12.715","Text":"with the energy investment than the uncatalyzed hill."},{"Start":"11:12.715 ","End":"11:15.650","Text":"Now, this top of the energy hill,"},{"Start":"11:15.650 ","End":"11:18.814","Text":"this is called the transition state,"},{"Start":"11:18.814 ","End":"11:25.550","Text":"where the decay to either S or P is equally probable is the transition state."},{"Start":"11:25.550 ","End":"11:30.140","Text":"The transition state is not a chemical species with any significant stability and"},{"Start":"11:30.140 ","End":"11:34.940","Text":"should not be confused with a reaction intermediate such as ES or EP,"},{"Start":"11:34.940 ","End":"11:37.850","Text":"the enzyme substrate complex or the enzyme product complex."},{"Start":"11:37.850 ","End":"11:41.900","Text":"It is simply a fleeting molecular moment in which events have proceeded to"},{"Start":"11:41.900 ","End":"11:48.094","Text":"the precise point at which decay to either substrate or product is equally likely."},{"Start":"11:48.094 ","End":"11:51.110","Text":"The difference between the energy levels of the ground state and"},{"Start":"11:51.110 ","End":"11:54.555","Text":"the transition state is the activation energy,"},{"Start":"11:54.555 ","End":"11:56.395","Text":"the Delta G double plus."},{"Start":"11:56.395 ","End":"11:59.240","Text":"The rate of a reaction reflects this activation energy."},{"Start":"11:59.240 ","End":"12:03.365","Text":"A higher activation energy corresponds to a slower reaction."},{"Start":"12:03.365 ","End":"12:07.850","Text":"Reaction rates can be increased by raising the temperature,"},{"Start":"12:07.850 ","End":"12:09.860","Text":"thereby increasing the number of molecules with"},{"Start":"12:09.860 ","End":"12:12.595","Text":"sufficient energy to overcome the energy barrier."},{"Start":"12:12.595 ","End":"12:14.210","Text":"Now to go over this,"},{"Start":"12:14.210 ","End":"12:16.190","Text":"we talked about increased temperature."},{"Start":"12:16.190 ","End":"12:19.055","Text":"Temperature is actually entropy and free energy."},{"Start":"12:19.055 ","End":"12:21.920","Text":"The minute you increase the temperature molecules,"},{"Start":"12:21.920 ","End":"12:25.490","Text":"the energy actually increases and movement of molecules."},{"Start":"12:25.490 ","End":"12:31.040","Text":"This allows overcoming the energy barrier in a rate that is higher."},{"Start":"12:31.040 ","End":"12:36.755","Text":"Alternatively, the activation energy can be lowered by adding a catalyst."},{"Start":"12:36.755 ","End":"12:42.050","Text":"What we\u0027re saying here is that there are two ways to increase the reaction rate."},{"Start":"12:42.050 ","End":"12:45.860","Text":"One is increasing the temperature, raising the temperature."},{"Start":"12:45.860 ","End":"12:47.480","Text":"Because when you raise the temperature,"},{"Start":"12:47.480 ","End":"12:50.120","Text":"you\u0027re actually increasing the free energy,"},{"Start":"12:50.120 ","End":"12:52.970","Text":"which means the number of molecules sufficient energy to"},{"Start":"12:52.970 ","End":"12:55.985","Text":"overcome the energy barrier has increased."},{"Start":"12:55.985 ","End":"13:00.890","Text":"The alternative is the activation and it can be lowered by adding a catalyst."},{"Start":"13:00.890 ","End":"13:04.490","Text":"Therefore, catalysts, which in our case are the enzymes,"},{"Start":"13:04.490 ","End":"13:08.974","Text":"enhance reaction rates by lowering activation energies."},{"Start":"13:08.974 ","End":"13:12.020","Text":"Again, the main take home point here is"},{"Start":"13:12.020 ","End":"13:15.920","Text":"catalyst enhanced reaction rates by lowering activation energies,"},{"Start":"13:15.920 ","End":"13:18.930","Text":"as seen in the figure, lower activation energy."},{"Start":"13:18.930 ","End":"13:20.780","Text":"With this, we completed Part 1 of"},{"Start":"13:20.780 ","End":"13:23.880","Text":"reaction rate and we introduced the idea of enzymes and reaction rate,"},{"Start":"13:23.880 ","End":"13:26.435","Text":"explained the role of enzymes as a catalyst."},{"Start":"13:26.435 ","End":"13:28.280","Text":"We related the term ground state,"},{"Start":"13:28.280 ","End":"13:30.695","Text":"transition state and activation energy."},{"Start":"13:30.695 ","End":"13:33.510","Text":"We\u0027ll meet up again in Part 2."}],"ID":30107},{"Watched":false,"Name":"Reaction Rates - Part 2","Duration":"7m 34s","ChapterTopicVideoID":28582,"CourseChapterTopicPlaylistID":286642,"HasSubtitles":true,"ThumbnailPath":null,"UploadDate":null,"DurationForVideoObject":null,"Description":null,"MetaTitle":null,"MetaDescription":null,"Canonical":null,"VideoComments":[],"Subtitles":[{"Start":"00:00.000 ","End":"00:05.425","Text":"We\u0027re back within how enzymes work and we\u0027re continuing our lesson on reaction rate,"},{"Start":"00:05.425 ","End":"00:06.660","Text":"this is Part 2."},{"Start":"00:06.660 ","End":"00:08.430","Text":"By the end of the section, you will be able to"},{"Start":"00:08.430 ","End":"00:10.710","Text":"describe reaction intermediates and relate"},{"Start":"00:10.710 ","End":"00:12.930","Text":"the rate-limiting step and activation energy and"},{"Start":"00:12.930 ","End":"00:16.770","Text":"the energy barrier related to enzymatic reactions."},{"Start":"00:16.770 ","End":"00:19.250","Text":"As we\u0027ve finished the previous part,"},{"Start":"00:19.250 ","End":"00:24.499","Text":"catalysts enhance reaction rates by lowering activation energies."},{"Start":"00:24.499 ","End":"00:29.285","Text":"We closed off Part 1 of this lesson stating this."},{"Start":"00:29.285 ","End":"00:35.015","Text":"Enzymes are no exception to the rule that catalysts do not affect reaction equilibria."},{"Start":"00:35.015 ","End":"00:38.180","Text":"This equation that we introduced previously stands"},{"Start":"00:38.180 ","End":"00:41.360","Text":"for enzyme plus substrate with the 2 intermediates,"},{"Start":"00:41.360 ","End":"00:47.840","Text":"enzyme substrate and enzyme product complexes resulting in enzyme and product."},{"Start":"00:47.840 ","End":"00:53.600","Text":"You see the bi-directional arrows in this equation make this point."},{"Start":"00:53.600 ","End":"00:58.750","Text":"Any enzyme that catalyzes the reaction S to P,"},{"Start":"00:58.750 ","End":"01:00.735","Text":"substrate to product,"},{"Start":"01:00.735 ","End":"01:05.104","Text":"also catalyzes the reaction, product to substrate."},{"Start":"01:05.104 ","End":"01:07.250","Text":"It is bi-directional."},{"Start":"01:07.250 ","End":"01:08.510","Text":"Re-emphasizing,"},{"Start":"01:08.510 ","End":"01:11.840","Text":"the enzymes do not affect the reaction equilibria and they"},{"Start":"01:11.840 ","End":"01:15.650","Text":"are responsible for the reaction going either direction."},{"Start":"01:15.650 ","End":"01:20.780","Text":"The role of enzymes is to accelerate the inter-conversion of S and"},{"Start":"01:20.780 ","End":"01:27.500","Text":"P. The enzyme is not used up in the process and the equilibrium point is unaffected."},{"Start":"01:27.500 ","End":"01:30.680","Text":"Now, this is a very important concept."},{"Start":"01:30.680 ","End":"01:36.860","Text":"Enzymes can repeat and do the process over and over, like recycle."},{"Start":"01:36.860 ","End":"01:40.340","Text":"However, the reaction reaches equilibrium much faster when"},{"Start":"01:40.340 ","End":"01:44.345","Text":"the appropriate enzyme is present because the rate of the reaction is increased."},{"Start":"01:44.345 ","End":"01:47.269","Text":"This general principle can be illustrated by considering"},{"Start":"01:47.269 ","End":"01:49.280","Text":"the following example of"},{"Start":"01:49.280 ","End":"01:53.150","Text":"the conversion of sucrose and oxygen to carbon dioxide and water."},{"Start":"01:53.150 ","End":"01:59.540","Text":"So you have sucrose and you have oxygen converted to carbon dioxide and H_2O, water."},{"Start":"01:59.540 ","End":"02:02.450","Text":"This conversion, which takes place through a series of separate reactions,"},{"Start":"02:02.450 ","End":"02:04.970","Text":"has a large, can even be generous and say,"},{"Start":"02:04.970 ","End":"02:08.510","Text":"a very large negative Delta G. At equilibrium,"},{"Start":"02:08.510 ","End":"02:11.735","Text":"the amount of sucrose present is negligible."},{"Start":"02:11.735 ","End":"02:15.890","Text":"It\u0027s sucrose is a stable compound because the activation energy barrier that must be"},{"Start":"02:15.890 ","End":"02:20.670","Text":"overcome before sucrose reacts with oxygen is quite high."},{"Start":"02:20.670 ","End":"02:25.460","Text":"Sucrose can be stored in a container with oxygen almost indefinitely without reacting."},{"Start":"02:25.460 ","End":"02:29.900","Text":"In cells, however, sucrose is readily broken down to CO_2 and"},{"Start":"02:29.900 ","End":"02:34.940","Text":"H_2O to carbon dioxide and water in a series of reactions catalyzed by enzymes."},{"Start":"02:34.940 ","End":"02:38.930","Text":"This is to say that this reaction doesn\u0027t just occur naturally,"},{"Start":"02:38.930 ","End":"02:41.720","Text":"you put sugar in a jar and nothing will happen."},{"Start":"02:41.720 ","End":"02:46.505","Text":"The enzymes in the cells play a key role in order to allow this to happen."},{"Start":"02:46.505 ","End":"02:51.530","Text":"The enzymes involved in these reactions not only accelerate the reactions,"},{"Start":"02:51.530 ","End":"02:56.390","Text":"they organize and control them so that much of the energy released is"},{"Start":"02:56.390 ","End":"03:02.560","Text":"recovered in other chemical forms and is made available to the cell for other tasks."},{"Start":"03:02.560 ","End":"03:06.410","Text":"This reaction pathway by which sucrose and other sugars is broken"},{"Start":"03:06.410 ","End":"03:10.595","Text":"down is the primary energy-yielding pathway for cells,"},{"Start":"03:10.595 ","End":"03:12.980","Text":"and the enzymes of this pathway allow"},{"Start":"03:12.980 ","End":"03:16.895","Text":"the reaction sequence to proceed on a biologically useful timescale."},{"Start":"03:16.895 ","End":"03:22.024","Text":"The cells rely on this reaction in order to have energy to carry out other functions."},{"Start":"03:22.024 ","End":"03:26.240","Text":"Any reaction may have several steps involving the formation and"},{"Start":"03:26.240 ","End":"03:31.025","Text":"decay of transient chemical species called reaction intermediates."},{"Start":"03:31.025 ","End":"03:35.540","Text":"The reaction intermediates are the species that are transient throughout"},{"Start":"03:35.540 ","End":"03:40.360","Text":"the several steps getting from the substrate to the product."},{"Start":"03:40.360 ","End":"03:43.340","Text":"A reaction intermediate is any species on"},{"Start":"03:43.340 ","End":"03:46.594","Text":"the reaction pathway that has a finite chemical lifetime,"},{"Start":"03:46.594 ","End":"03:49.655","Text":"which means it\u0027s longer than a molecular vibration,"},{"Start":"03:49.655 ","End":"03:53.560","Text":"which is about 10^negative 13 seconds."},{"Start":"03:53.560 ","End":"03:58.235","Text":"When the S to product reaction is catalyzed by an enzyme,"},{"Start":"03:58.235 ","End":"04:02.990","Text":"the ES and EP complexes can be considered intermediates."},{"Start":"04:02.990 ","End":"04:07.181","Text":"Even though S and P,"},{"Start":"04:07.181 ","End":"04:09.875","Text":"substrate and product, are stable chemical species,"},{"Start":"04:09.875 ","End":"04:12.770","Text":"the ES, enzyme substrate complex, and the EP,"},{"Start":"04:12.770 ","End":"04:14.060","Text":"enzyme product complexes,"},{"Start":"04:14.060 ","End":"04:17.690","Text":"occupy valleys in the reaction coordinate diagram."},{"Start":"04:17.690 ","End":"04:20.180","Text":"If you\u0027re looking at the reaction coordinate diagram,"},{"Start":"04:20.180 ","End":"04:23.075","Text":"you see the hill that\u0027s uncatalyzed,"},{"Start":"04:23.075 ","End":"04:27.590","Text":"and with the catalysis by an enzyme where the hill, this barrier,"},{"Start":"04:27.590 ","End":"04:30.290","Text":"this energy barrier, is minimized;"},{"Start":"04:30.290 ","End":"04:34.685","Text":"you see the ES and EP complex"},{"Start":"04:34.685 ","End":"04:40.430","Text":"actually occupying this valley in the reaction coordinate diagram."},{"Start":"04:40.430 ","End":"04:42.290","Text":"You have these little hills,"},{"Start":"04:42.290 ","End":"04:49.570","Text":"and in the valley of these little energy barriers you see the complexes occupying them."},{"Start":"04:49.570 ","End":"04:51.975","Text":"In this reaction,"},{"Start":"04:51.975 ","End":"04:56.660","Text":"these occupy the little dips in the energy in"},{"Start":"04:56.660 ","End":"05:03.045","Text":"the process of forming S to P or P to S. Additional,"},{"Start":"05:03.045 ","End":"05:05.515","Text":"less stable chemical intermediates"},{"Start":"05:05.515 ","End":"05:08.455","Text":"often exist in the course of an enzyme-catalyzed reaction."},{"Start":"05:08.455 ","End":"05:13.135","Text":"The interconversion of 2 sequential reaction intermediates"},{"Start":"05:13.135 ","End":"05:15.130","Text":"thus constitutes a reaction step."},{"Start":"05:15.130 ","End":"05:17.500","Text":"When several steps occur in a reaction,"},{"Start":"05:17.500 ","End":"05:24.070","Text":"the overall rate is determined by the step or steps with the highest activation energy."},{"Start":"05:24.070 ","End":"05:26.980","Text":"This is called the rate-limiting step."},{"Start":"05:26.980 ","End":"05:28.180","Text":"In a simple case,"},{"Start":"05:28.180 ","End":"05:32.200","Text":"the rate-limiting step is the highest energy point in the diagram for"},{"Start":"05:32.200 ","End":"05:36.625","Text":"interconversion of S and P. In practice,"},{"Start":"05:36.625 ","End":"05:40.435","Text":"the rate-limiting step can vary with reaction conditions."},{"Start":"05:40.435 ","End":"05:45.500","Text":"For many enzymes, several steps may have similar activation energies,"},{"Start":"05:45.500 ","End":"05:48.830","Text":"which means they all are partially rate-limiting."},{"Start":"05:48.830 ","End":"05:53.329","Text":"Activation energies are energy barriers to chemical reactions."},{"Start":"05:53.329 ","End":"05:57.710","Text":"These barriers are crucial to life itself and the rate at which a molecule undergoes"},{"Start":"05:57.710 ","End":"06:03.230","Text":"a particular reaction decreases as the activation barrier for that reaction increases."},{"Start":"06:03.230 ","End":"06:05.690","Text":"The higher the activation barrier,"},{"Start":"06:05.690 ","End":"06:10.430","Text":"the rate at which a molecule undergoes that reaction,"},{"Start":"06:10.430 ","End":"06:12.665","Text":"meaning the rate of the reaction occurring,"},{"Start":"06:12.665 ","End":"06:15.355","Text":"the higher the activation barrier is,"},{"Start":"06:15.355 ","End":"06:20.390","Text":"decreases, meaning a slower reaction when there\u0027s a higher activation barrier."},{"Start":"06:20.390 ","End":"06:22.130","Text":"If there\u0027s a lower activation barrier,"},{"Start":"06:22.130 ","End":"06:23.810","Text":"the reaction can occur faster,"},{"Start":"06:23.810 ","End":"06:26.405","Text":"more easily, and the rate increases."},{"Start":"06:26.405 ","End":"06:28.430","Text":"Without such energy barriers,"},{"Start":"06:28.430 ","End":"06:33.950","Text":"complex macromolecules would revert spontaneously to much simpler molecular forms,"},{"Start":"06:33.950 ","End":"06:37.070","Text":"and the complex and highly ordered structures and"},{"Start":"06:37.070 ","End":"06:42.160","Text":"metabolic processes of cells would not and could not exist."},{"Start":"06:42.160 ","End":"06:43.925","Text":"Over the course of evolution,"},{"Start":"06:43.925 ","End":"06:47.270","Text":"enzymes have developed lower activation energy"},{"Start":"06:47.270 ","End":"06:51.155","Text":"selectively for reactions that are needed for cell survival,"},{"Start":"06:51.155 ","End":"06:58.500","Text":"and this is why enzymes play such a crucial role in viability in life,"},{"Start":"06:58.500 ","End":"07:02.100","Text":"in cell production and cell function."},{"Start":"07:02.100 ","End":"07:06.650","Text":"This goes back to the idea that catalysis of"},{"Start":"07:06.650 ","End":"07:12.715","Text":"reactions in cells is needed and reliant on enzymes."},{"Start":"07:12.715 ","End":"07:18.880","Text":"With this, we completed the lesson on reaction rate within the top of how enzymes work."},{"Start":"07:18.880 ","End":"07:22.520","Text":"You should be able to understand enzymes and reaction rate,"},{"Start":"07:22.520 ","End":"07:24.860","Text":"explain the role of an enzyme as a catalyst,"},{"Start":"07:24.860 ","End":"07:27.945","Text":"and relate the term ground state, transition state,"},{"Start":"07:27.945 ","End":"07:29.745","Text":"and activation energy,"},{"Start":"07:29.745 ","End":"07:34.410","Text":"we also introduced the term reaction intermediates, etc."}],"ID":30108},{"Watched":false,"Name":"Exercise 3","Duration":"47s","ChapterTopicVideoID":28583,"CourseChapterTopicPlaylistID":286642,"HasSubtitles":true,"ThumbnailPath":null,"UploadDate":null,"DurationForVideoObject":null,"Description":null,"MetaTitle":null,"MetaDescription":null,"Canonical":null,"VideoComments":[],"Subtitles":[{"Start":"00:00.000 ","End":"00:05.100","Text":"We\u0027re within reaction rate and we are going to go over an exercise."},{"Start":"00:05.100 ","End":"00:06.690","Text":"In the context of enzymes,"},{"Start":"00:06.690 ","End":"00:09.075","Text":"explain the significance of the phrase below."},{"Start":"00:09.075 ","End":"00:14.250","Text":"What we see here is enzyme plus substrate interconversion into enzyme substrate,"},{"Start":"00:14.250 ","End":"00:17.820","Text":"enzyme product, and enzyme plus product."},{"Start":"00:17.820 ","End":"00:21.945","Text":"This was a hint as to our answer."},{"Start":"00:21.945 ","End":"00:28.184","Text":"This is a representation of a simple enzymatic reaction where E represents the enzyme,"},{"Start":"00:28.184 ","End":"00:30.402","Text":"S represents substrate,"},{"Start":"00:30.402 ","End":"00:33.865","Text":"and P represents product."},{"Start":"00:33.865 ","End":"00:38.055","Text":"ES is a transient complex of the enzyme with the substrate"},{"Start":"00:38.055 ","End":"00:42.605","Text":"and EP is a transient complex of the enzyme with the product."},{"Start":"00:42.605 ","End":"00:47.130","Text":"These can be considered reaction intermediates."}],"ID":30109},{"Watched":false,"Name":"Exercise 4","Duration":"1m 8s","ChapterTopicVideoID":28624,"CourseChapterTopicPlaylistID":286642,"HasSubtitles":true,"ThumbnailPath":null,"UploadDate":null,"DurationForVideoObject":null,"Description":null,"MetaTitle":null,"MetaDescription":null,"Canonical":null,"VideoComments":[],"Subtitles":[{"Start":"00:00.000 ","End":"00:03.570","Text":"Welcome to another exercise within reaction`1 rate."},{"Start":"00:03.570 ","End":"00:07.395","Text":"Complete the sentence and explain its significance to enzymes."},{"Start":"00:07.395 ","End":"00:15.225","Text":"Enzymes affect reaction blank and not blank."},{"Start":"00:15.225 ","End":"00:17.235","Text":"We went over this a few times."},{"Start":"00:17.235 ","End":"00:23.369","Text":"Enzymes affect reaction rates and not equilibria of the reaction."},{"Start":"00:23.369 ","End":"00:26.145","Text":"This concept is important to understanding catalysis,"},{"Start":"00:26.145 ","End":"00:29.670","Text":"which is the role of enzymes in reactions in cells and in life."},{"Start":"00:29.670 ","End":"00:34.335","Text":"It is important to grasp the distinction between reaction equilibrium and reaction rates."},{"Start":"00:34.335 ","End":"00:38.580","Text":"The function of a catalyst is to increase the rate of a reaction."},{"Start":"00:38.580 ","End":"00:42.405","Text":"Catalysts do not affect reaction equilibrium."},{"Start":"00:42.405 ","End":"00:46.445","Text":"I\u0027ve mentioned this and repeated it throughout the lessons."},{"Start":"00:46.445 ","End":"00:50.230","Text":"This is a very important concept to understand."},{"Start":"00:50.230 ","End":"00:54.290","Text":"Enzymes affect reaction path in the fact that it"},{"Start":"00:54.290 ","End":"00:58.235","Text":"allows the reaction to proceed in a favorable direction for"},{"Start":"00:58.235 ","End":"01:02.630","Text":"self function at an increased rate that otherwise would"},{"Start":"01:02.630 ","End":"01:08.190","Text":"take longer or not occur unless in very specific conditions."}],"ID":30110},{"Watched":false,"Name":"Exercise 5","Duration":"59s","ChapterTopicVideoID":28584,"CourseChapterTopicPlaylistID":286642,"HasSubtitles":true,"ThumbnailPath":null,"UploadDate":null,"DurationForVideoObject":null,"Description":null,"MetaTitle":null,"MetaDescription":null,"Canonical":null,"VideoComments":[],"Subtitles":[{"Start":"00:00.000 ","End":"00:03.435","Text":"We are testing our knowledge on reaction rates."},{"Start":"00:03.435 ","End":"00:06.600","Text":"Define and explain the term ground state."},{"Start":"00:06.600 ","End":"00:13.095","Text":"The starting point for the forward or reverse reaction is called the ground state."},{"Start":"00:13.095 ","End":"00:14.590","Text":"In chemistry and physics,"},{"Start":"00:14.590 ","End":"00:15.930","Text":"the ground state is defined as"},{"Start":"00:15.930 ","End":"00:19.725","Text":"the lowest allowed energy state of an atom, molecule, or ion."},{"Start":"00:19.725 ","End":"00:25.020","Text":"In other words, the ground state represents the most stable configuration."},{"Start":"00:25.020 ","End":"00:28.470","Text":"Even though the species may possess some level of energy,"},{"Start":"00:28.470 ","End":"00:34.940","Text":"the ground state is considered to have zero-point energy in comparison to other states."},{"Start":"00:34.940 ","End":"00:38.600","Text":"Electrons provide a good example of ground and excited states."},{"Start":"00:38.600 ","End":"00:40.969","Text":"If an electron absorbs energy,"},{"Start":"00:40.969 ","End":"00:43.130","Text":"it may jump to an excited state,"},{"Start":"00:43.130 ","End":"00:44.630","Text":"and at some point,"},{"Start":"00:44.630 ","End":"00:47.270","Text":"the electron will return to the ground state"},{"Start":"00:47.270 ","End":"00:50.870","Text":"typically giving off a photon in the process."},{"Start":"00:50.870 ","End":"00:54.275","Text":"Now if you remember in lesson we introduced a figure to explain this."},{"Start":"00:54.275 ","End":"01:00.210","Text":"Go back to that if the concept is not solidified in your head."}],"ID":30111},{"Watched":false,"Name":"Exercise 6","Duration":"2m 8s","ChapterTopicVideoID":28569,"CourseChapterTopicPlaylistID":286642,"HasSubtitles":true,"ThumbnailPath":null,"UploadDate":null,"DurationForVideoObject":null,"Description":null,"MetaTitle":null,"MetaDescription":null,"Canonical":null,"VideoComments":[],"Subtitles":[{"Start":"00:00.000 ","End":"00:03.615","Text":"Hi there. What did we learn about reaction rate?"},{"Start":"00:03.615 ","End":"00:08.340","Text":"The position and direction of equilibrium are not affected by any catalyst,"},{"Start":"00:08.340 ","End":"00:10.875","Text":"rather, it affects the rate of reaction."},{"Start":"00:10.875 ","End":"00:12.600","Text":"How does it do so?"},{"Start":"00:12.600 ","End":"00:17.235","Text":"The rate of a reaction is dependent on a parameter that enzymes help overcome."},{"Start":"00:17.235 ","End":"00:21.975","Text":"There\u0027s an energy barrier between S and P, substrate and product."},{"Start":"00:21.975 ","End":"00:26.330","Text":"It is the energy required for alignment of reacting groups,"},{"Start":"00:26.330 ","End":"00:28.640","Text":"bonds rearrangements, and other transformations"},{"Start":"00:28.640 ","End":"00:32.540","Text":"required for the reaction to proceed in either direction."},{"Start":"00:32.540 ","End":"00:35.330","Text":"This is illustrated by the energy hill that we"},{"Start":"00:35.330 ","End":"00:38.330","Text":"had shown in the figures presented in the lesson."},{"Start":"00:38.330 ","End":"00:40.295","Text":"For a reaction to proceed,"},{"Start":"00:40.295 ","End":"00:43.100","Text":"the molecules must overcome this barrier and"},{"Start":"00:43.100 ","End":"00:46.355","Text":"therefore must be raised to a higher energy level."},{"Start":"00:46.355 ","End":"00:50.015","Text":"Reaction rates can be increased by raising the temperature,"},{"Start":"00:50.015 ","End":"00:52.100","Text":"thereby increasing the number of molecules with"},{"Start":"00:52.100 ","End":"00:56.180","Text":"sufficient energy to overcome the energy barrier."},{"Start":"00:56.180 ","End":"01:02.015","Text":"Alternatively, the activation energy can be lowered by adding a catalyst."},{"Start":"01:02.015 ","End":"01:05.015","Text":"We see here, if we increase temperature,"},{"Start":"01:05.015 ","End":"01:07.580","Text":"if we raise temperature it means the energy present"},{"Start":"01:07.580 ","End":"01:10.415","Text":"within the reaction with the molecules,"},{"Start":"01:10.415 ","End":"01:12.320","Text":"and with this increase in energy,"},{"Start":"01:12.320 ","End":"01:17.375","Text":"it makes it closer to this barrier, this hill."},{"Start":"01:17.375 ","End":"01:21.620","Text":"This energy barrier that it needs to overcome in order for the reaction to take place."},{"Start":"01:21.620 ","End":"01:27.125","Text":"The other methodology is a catalyst lowering this hill,"},{"Start":"01:27.125 ","End":"01:29.220","Text":"reducing it to a lower state."},{"Start":"01:29.220 ","End":"01:31.010","Text":"Instead of being up here,"},{"Start":"01:31.010 ","End":"01:36.075","Text":"it\u0027s reduced the hill size down here, all the way here."},{"Start":"01:36.075 ","End":"01:39.170","Text":"Now the energy investment, the Delta G,"},{"Start":"01:39.170 ","End":"01:44.030","Text":"that needs to be in order for S to convert to P and vice versa,"},{"Start":"01:44.030 ","End":"01:48.110","Text":"is a smaller Delta G than this big Delta G,"},{"Start":"01:48.110 ","End":"01:54.164","Text":"and therefore this catalyst allows the reaction to occur."},{"Start":"01:54.164 ","End":"01:59.375","Text":"This catalyst enhances reaction rate by lowering activation energy."},{"Start":"01:59.375 ","End":"02:03.530","Text":"As we mentioned, these catalysts in life,"},{"Start":"02:03.530 ","End":"02:08.310","Text":"in cells, are played by the roles of enzymes."}],"ID":30112},{"Watched":false,"Name":"Exercise 7","Duration":"1m 57s","ChapterTopicVideoID":28570,"CourseChapterTopicPlaylistID":286642,"HasSubtitles":true,"ThumbnailPath":null,"UploadDate":null,"DurationForVideoObject":null,"Description":null,"MetaTitle":null,"MetaDescription":null,"Canonical":null,"VideoComments":[],"Subtitles":[{"Start":"00:00.000 ","End":"00:01.200","Text":"We\u0027re within reaction rate,"},{"Start":"00:01.200 ","End":"00:02.699","Text":"and we have another exercise."},{"Start":"00:02.699 ","End":"00:04.650","Text":"What is the transition state?"},{"Start":"00:04.650 ","End":"00:08.040","Text":"The transition state is not a chemical species with"},{"Start":"00:08.040 ","End":"00:11.970","Text":"any significant stability and should not be confused with the reaction intermediates such"},{"Start":"00:11.970 ","End":"00:14.280","Text":"as ES or P. It is simply"},{"Start":"00:14.280 ","End":"00:19.140","Text":"a fleeting molecular moment in which events such as bond breakage,"},{"Start":"00:19.140 ","End":"00:21.600","Text":"bond formation, and charge development have"},{"Start":"00:21.600 ","End":"00:24.120","Text":"proceeded to the precise point at which decay"},{"Start":"00:24.120 ","End":"00:29.565","Text":"to either substrate or product is equally likely."},{"Start":"00:29.565 ","End":"00:31.965","Text":"At the top of the energy hill,"},{"Start":"00:31.965 ","End":"00:35.490","Text":"the highest point of energy barrier is a point at which decay to"},{"Start":"00:35.490 ","End":"00:38.977","Text":"the S or P substrate or a product state is equally probable;"},{"Start":"00:38.977 ","End":"00:41.360","Text":"it is downhill either way."},{"Start":"00:41.360 ","End":"00:44.210","Text":"This is called the transition state."},{"Start":"00:44.210 ","End":"00:45.680","Text":"The top of the hill,"},{"Start":"00:45.680 ","End":"00:48.155","Text":"the highest point of the hill."},{"Start":"00:48.155 ","End":"00:51.635","Text":"The top of the energy hill is the energy hill,"},{"Start":"00:51.635 ","End":"00:57.064","Text":"and it is downhill either way to product or substrate."},{"Start":"00:57.064 ","End":"00:59.690","Text":"These are 2 figures we introduced in the lesson."},{"Start":"00:59.690 ","End":"01:01.835","Text":"They represent the same thing,"},{"Start":"01:01.835 ","End":"01:04.190","Text":"they just emphasize different things."},{"Start":"01:04.190 ","End":"01:10.385","Text":"Here we\u0027re looking at the Delta G between substrate and product."},{"Start":"01:10.385 ","End":"01:12.490","Text":"You have a delta G here,"},{"Start":"01:12.490 ","End":"01:14.141","Text":"uncatalyzed versus catalyzed,"},{"Start":"01:14.141 ","End":"01:18.835","Text":"and here you also see the intermediate complexes."},{"Start":"01:18.835 ","End":"01:23.491","Text":"That\u0027s it, the valley of the energy of the hills of the energy barrier,"},{"Start":"01:23.491 ","End":"01:30.259","Text":"and here you see the Delta G of the substrate to product versus the product to substrate."},{"Start":"01:30.259 ","End":"01:33.560","Text":"This is a bigger change because"},{"Start":"01:33.560 ","End":"01:38.284","Text":"the product ground-state is lower than the substrate ground-state."},{"Start":"01:38.284 ","End":"01:43.175","Text":"Same figures showing transition state, the energy hill,"},{"Start":"01:43.175 ","End":"01:46.670","Text":"and the reaction of substrate to product or product to"},{"Start":"01:46.670 ","End":"01:51.340","Text":"substrate and the key point in this is we\u0027re talking about the transition state;"},{"Start":"01:51.340 ","End":"01:57.270","Text":"that top of the hill for which it\u0027s downhill to either direction for S or P."}],"ID":30113},{"Watched":false,"Name":"Exercise 8","Duration":"35s","ChapterTopicVideoID":28571,"CourseChapterTopicPlaylistID":286642,"HasSubtitles":true,"ThumbnailPath":null,"UploadDate":null,"DurationForVideoObject":null,"Description":null,"MetaTitle":null,"MetaDescription":null,"Canonical":null,"VideoComments":[],"Subtitles":[{"Start":"00:00.000 ","End":"00:03.315","Text":"We\u0027re testing our knowledge on reaction rates"},{"Start":"00:03.315 ","End":"00:06.795","Text":"in reference to the ground state and transition state."},{"Start":"00:06.795 ","End":"00:09.450","Text":"What is the activation energy?"},{"Start":"00:09.450 ","End":"00:13.020","Text":"The difference between the energy levels of the ground state,"},{"Start":"00:13.020 ","End":"00:18.150","Text":"which can be described as the starting point for the reaction and the transition state,"},{"Start":"00:18.150 ","End":"00:20.610","Text":"which is the highest point of the energy barrier,"},{"Start":"00:20.610 ","End":"00:22.439","Text":"is the activation energy,"},{"Start":"00:22.439 ","End":"00:23.955","Text":"Delta G plus, plus."},{"Start":"00:23.955 ","End":"00:28.620","Text":"The rate of any reaction reflects this activation energy."},{"Start":"00:28.620 ","End":"00:33.430","Text":"A higher activation energy corresponds to a slower reaction."}],"ID":30114},{"Watched":false,"Name":"Exercise 9","Duration":"1m 8s","ChapterTopicVideoID":28572,"CourseChapterTopicPlaylistID":286642,"HasSubtitles":true,"ThumbnailPath":null,"UploadDate":null,"DurationForVideoObject":null,"Description":null,"MetaTitle":null,"MetaDescription":null,"Canonical":null,"VideoComments":[],"Subtitles":[{"Start":"00:00.000 ","End":"00:02.790","Text":"We have another exercise within reaction rate."},{"Start":"00:02.790 ","End":"00:04.186","Text":"Complete the sentence,"},{"Start":"00:04.186 ","End":"00:07.155","Text":"the enzymes not only accelerate the reactions,"},{"Start":"00:07.155 ","End":"00:12.870","Text":"they blank and blank them so that the energy released is made blank,"},{"Start":"00:12.870 ","End":"00:15.750","Text":"to the cell for other blank."},{"Start":"00:15.750 ","End":"00:17.520","Text":"We talked about a couple of times,"},{"Start":"00:17.520 ","End":"00:23.798","Text":"this main point of what enzymes do and what they don\u0027t do,"},{"Start":"00:23.798 ","End":"00:30.680","Text":"and we completed the lesson with mentioning enzymes having additional roles."},{"Start":"00:30.680 ","End":"00:33.395","Text":"The reactions can have a few steps."},{"Start":"00:33.395 ","End":"00:35.810","Text":"What role does the enzyme play in this?"},{"Start":"00:35.810 ","End":"00:39.130","Text":"Well, they organize these steps, these reactions,"},{"Start":"00:39.130 ","End":"00:41.455","Text":"and they control them,"},{"Start":"00:41.455 ","End":"00:43.189","Text":"so that the energy released,"},{"Start":"00:43.189 ","End":"00:46.295","Text":"which is needed for many function,"},{"Start":"00:46.295 ","End":"00:51.620","Text":"is made available to the cell for other things that need to happen,"},{"Start":"00:51.620 ","End":"00:53.680","Text":"to occur for other reactions."},{"Start":"00:53.680 ","End":"00:56.945","Text":"The enzymes not only accelerate the reactions,"},{"Start":"00:56.945 ","End":"01:01.940","Text":"they organize and control them so that the energy released is recovered"},{"Start":"01:01.940 ","End":"01:08.070","Text":"in other chemical forms and made available to the cell for other tasks."}],"ID":30115},{"Watched":false,"Name":"Exercise 10","Duration":"1m 37s","ChapterTopicVideoID":28573,"CourseChapterTopicPlaylistID":286642,"HasSubtitles":true,"ThumbnailPath":null,"UploadDate":null,"DurationForVideoObject":null,"Description":null,"MetaTitle":null,"MetaDescription":null,"Canonical":null,"VideoComments":[],"Subtitles":[{"Start":"00:00.000 ","End":"00:02.880","Text":"Let\u0027s dive into another exercise within reaction rate."},{"Start":"00:02.880 ","End":"00:06.330","Text":"Define the reaction intermediates and the rate-limiting step."},{"Start":"00:06.330 ","End":"00:09.420","Text":"We introduced many terms during this lesson."},{"Start":"00:09.420 ","End":"00:14.570","Text":"A reaction intermediate is any species on the reaction pathway"},{"Start":"00:14.570 ","End":"00:19.325","Text":"that has a finite chemical lifetime longer than a molecular vibration,"},{"Start":"00:19.325 ","End":"00:24.020","Text":"which is approximately 10^negative 13 seconds."},{"Start":"00:24.020 ","End":"00:27.650","Text":"When the substrate product reaction is catalyzed by an enzyme,"},{"Start":"00:27.650 ","End":"00:31.205","Text":"the ES and EP complexes can be considered intermediate."},{"Start":"00:31.205 ","End":"00:34.790","Text":"We\u0027re talking about the enzyme-substrate and the enzyme product complexes."},{"Start":"00:34.790 ","End":"00:38.480","Text":"Any reaction may have several steps involving the formation and decay of"},{"Start":"00:38.480 ","End":"00:42.485","Text":"transient chemical species called reaction intermediates."},{"Start":"00:42.485 ","End":"00:45.590","Text":"Additional less stable chemical intermediates"},{"Start":"00:45.590 ","End":"00:48.637","Text":"often exist in the course of an enzyme-catalyzed reaction."},{"Start":"00:48.637 ","End":"00:51.950","Text":"The interconversion of 2 sequential reaction intermediates"},{"Start":"00:51.950 ","End":"00:54.625","Text":"thus constitutes a reaction step."},{"Start":"00:54.625 ","End":"00:56.790","Text":"When several steps occur in a reaction,"},{"Start":"00:56.790 ","End":"01:00.665","Text":"the overall rate is determined by the step with the highest activation energy."},{"Start":"01:00.665 ","End":"01:02.940","Text":"This also can refer to steps."},{"Start":"01:02.940 ","End":"01:04.880","Text":"Meaning whatever steps occur in a reaction,"},{"Start":"01:04.880 ","End":"01:09.320","Text":"the overall rate is determined by the step or steps with the highest activation energy."},{"Start":"01:09.320 ","End":"01:12.055","Text":"This is called the rate-limiting step."},{"Start":"01:12.055 ","End":"01:14.240","Text":"Again, there could be a couple of these."},{"Start":"01:14.240 ","End":"01:16.430","Text":"In a simple case, the rate-limiting steps,"},{"Start":"01:16.430 ","End":"01:19.670","Text":"the highest energy point in the diagram for interconversion"},{"Start":"01:19.670 ","End":"01:23.720","Text":"of substrate in product S and P. In practice,"},{"Start":"01:23.720 ","End":"01:26.825","Text":"the rate-limiting step can vary with reaction conditions."},{"Start":"01:26.825 ","End":"01:31.505","Text":"For many enzymes, several steps may have similar activation energies,"},{"Start":"01:31.505 ","End":"01:37.230","Text":"which means they are partially or all partially rate-limiting."}],"ID":30116},{"Watched":false,"Name":"Reaction Rates and Thermodynamics","Duration":"7m 48s","ChapterTopicVideoID":28574,"CourseChapterTopicPlaylistID":286642,"HasSubtitles":true,"ThumbnailPath":null,"UploadDate":null,"DurationForVideoObject":null,"Description":null,"MetaTitle":null,"MetaDescription":null,"Canonical":null,"VideoComments":[],"Subtitles":[{"Start":"00:00.000 ","End":"00:03.120","Text":"We\u0027re learning about how enzymes work and we"},{"Start":"00:03.120 ","End":"00:05.490","Text":"introduced the concepts of reaction rate and everything"},{"Start":"00:05.490 ","End":"00:10.455","Text":"related to it and now we are going to associate it with thermodynamics,"},{"Start":"00:10.455 ","End":"00:13.095","Text":"which we\u0027ve introduced in a previous chapter."},{"Start":"00:13.095 ","End":"00:14.970","Text":"In this section, we will learn about"},{"Start":"00:14.970 ","End":"00:17.190","Text":"the enzyme reaction equilibrium constant and rate"},{"Start":"00:17.190 ","End":"00:20.205","Text":"constant and enzyme reaction of rate equation."},{"Start":"00:20.205 ","End":"00:24.960","Text":"Reaction equilibria are inextricably linked to the standard free energy change for"},{"Start":"00:24.960 ","End":"00:31.005","Text":"the reaction Delta G and reaction rates are linked to the activation energy Delta G++."},{"Start":"00:31.005 ","End":"00:34.935","Text":"Going back to the figure we introduced in the previous lesson,"},{"Start":"00:34.935 ","End":"00:38.085","Text":"you have this activation energy,"},{"Start":"00:38.085 ","End":"00:42.155","Text":"as you could see it right here."},{"Start":"00:42.155 ","End":"00:43.430","Text":"A basic introduction to"},{"Start":"00:43.430 ","End":"00:47.600","Text":"these thermodynamic relationships is important in understanding how enzymes work."},{"Start":"00:47.600 ","End":"00:51.950","Text":"Going back to the previous lesson using the simple enzymatic reaction that"},{"Start":"00:51.950 ","End":"00:56.480","Text":"we expressed as E plus S goes to the ES complex,"},{"Start":"00:56.480 ","End":"01:00.430","Text":"EP complex and results in E plus product."},{"Start":"01:00.430 ","End":"01:02.510","Text":"An equilibrium such as"},{"Start":"01:02.510 ","End":"01:08.910","Text":"the SP interconversion is described by an equilibrium constant K_eq,"},{"Start":"01:09.280 ","End":"01:12.275","Text":"K equilibrium, or for short,"},{"Start":"01:12.275 ","End":"01:16.760","Text":"just K. This we introduced in the thermodynamics lessons."},{"Start":"01:16.760 ","End":"01:22.360","Text":"Under the standard conditions used to compare biochemical processes,"},{"Start":"01:22.360 ","End":"01:28.625","Text":"an equilibrium constant is denoted K\u0027 equilibrium or K\u0027 and you see the formula here."},{"Start":"01:28.625 ","End":"01:35.210","Text":"K\u0027 equilibrium is the concentration of product over the concentration of substrates."},{"Start":"01:35.210 ","End":"01:39.545","Text":"This is as we had product over"},{"Start":"01:39.545 ","End":"01:48.545","Text":"reactant when we were calculating the equilibrium constant in chemical reactions."},{"Start":"01:48.545 ","End":"01:55.160","Text":"Here we\u0027re just using the term substrate for reactant and product,"},{"Start":"01:55.160 ","End":"01:57.100","Text":"the substrate for an enzymatic reaction."},{"Start":"01:57.100 ","End":"01:59.690","Text":"For thermodynamics, the relationship between"},{"Start":"01:59.690 ","End":"02:03.935","Text":"K\u0027 equilibrium and Delta G\u0027 can be described by this expression."},{"Start":"02:03.935 ","End":"02:09.680","Text":"Delta G\u0027 equals negative RT natural log of K\u0027 equilibrium,"},{"Start":"02:09.680 ","End":"02:14.155","Text":"where R is the gas constant and it\u0027s 8.315 joules per"},{"Start":"02:14.155 ","End":"02:20.030","Text":"mole and K and T is the absolute temperature,"},{"Start":"02:20.030 ","End":"02:24.620","Text":"298 Kelvin or 25 degrees Celsius."},{"Start":"02:24.620 ","End":"02:27.785","Text":"But this is what is used for this."},{"Start":"02:27.785 ","End":"02:30.725","Text":"These terms had been introduced in previous lessons."},{"Start":"02:30.725 ","End":"02:34.880","Text":"The important point here is that the equilibrium constant is"},{"Start":"02:34.880 ","End":"02:39.770","Text":"directly related to the overall standard free-energy change for the reaction."},{"Start":"02:39.770 ","End":"02:47.135","Text":"A large negative value for Delta G reflects a favorable reaction equilibrium."},{"Start":"02:47.135 ","End":"02:48.260","Text":"But as already noted,"},{"Start":"02:48.260 ","End":"02:52.985","Text":"this does not mean that reaction will proceed at a rapid rate,"},{"Start":"02:52.985 ","End":"02:55.200","Text":"but at large Delta G,"},{"Start":"02:55.200 ","End":"03:00.170","Text":"negative Delta G, this means it\u0027s going down,"},{"Start":"03:00.170 ","End":"03:03.515","Text":"means a favorable reaction."},{"Start":"03:03.515 ","End":"03:06.950","Text":"The rate of any reaction is determined by the concentration"},{"Start":"03:06.950 ","End":"03:10.160","Text":"of the reactant or reactants and by"},{"Start":"03:10.160 ","End":"03:16.970","Text":"a rate constant usually denoted by K. For the unimolecular reaction S to P,"},{"Start":"03:16.970 ","End":"03:21.545","Text":"substrate to product, the rate or velocity of the reaction,"},{"Start":"03:21.545 ","End":"03:24.060","Text":"V, rate of velocity,"},{"Start":"03:24.060 ","End":"03:27.410","Text":"so V for velocity representing the amount of substrate that"},{"Start":"03:27.410 ","End":"03:30.859","Text":"reacts per unit time is expressed by a rate equation,"},{"Start":"03:30.859 ","End":"03:33.980","Text":"V velocity equals the constant K,"},{"Start":"03:33.980 ","End":"03:38.475","Text":"the rate constant times the concentration of the substrate."},{"Start":"03:38.475 ","End":"03:43.370","Text":"In this reaction, the rate depends only on the concentration of S,"},{"Start":"03:43.370 ","End":"03:47.420","Text":"that is actually what is changing since K is a constant."},{"Start":"03:47.420 ","End":"03:50.360","Text":"This is called a first order"},{"Start":"03:50.360 ","End":"03:55.160","Text":"reaction because it\u0027s dependent just on the substrate concentration."},{"Start":"03:55.160 ","End":"03:58.760","Text":"The factor K is a proportionality constant that reflects"},{"Start":"03:58.760 ","End":"04:02.389","Text":"the probability of reaction under a given set of conditions,"},{"Start":"04:02.389 ","End":"04:05.200","Text":"pH, temperature and so forth."},{"Start":"04:05.200 ","End":"04:11.120","Text":"Here, K is a first-order rate constant and has units of reciprocal time,"},{"Start":"04:11.120 ","End":"04:15.140","Text":"such as seconds to the power of negative 1."},{"Start":"04:15.140 ","End":"04:21.215","Text":"If a first-order reaction has a rate constant K of 0.03 seconds and negative 1,"},{"Start":"04:21.215 ","End":"04:25.250","Text":"this may be interpreted qualitatively to mean that"},{"Start":"04:25.250 ","End":"04:32.310","Text":"3% of the available substrate will be converted to product in 1 second."},{"Start":"04:32.310 ","End":"04:38.180","Text":"The 3% comes from 0.03 because"},{"Start":"04:38.180 ","End":"04:45.810","Text":"percent is 1/100 or X/100,"},{"Start":"04:45.810 ","End":"04:48.480","Text":"this is 1% for example, percent."},{"Start":"04:48.480 ","End":"04:52.080","Text":"X/100 means X%."},{"Start":"04:52.080 ","End":"04:53.385","Text":"Taking this,"},{"Start":"04:53.385 ","End":"04:55.530","Text":"this is divided by 10,"},{"Start":"04:55.530 ","End":"04:56.715","Text":"this is divided by 100."},{"Start":"04:56.715 ","End":"05:00.780","Text":"So 0.03 equals"},{"Start":"05:00.780 ","End":"05:08.065","Text":"3/100 or 3^-2."},{"Start":"05:08.065 ","End":"05:12.740","Text":"Basically this means 3% of"},{"Start":"05:12.740 ","End":"05:18.030","Text":"the available substrate can be converted to product in 1 second."},{"Start":"05:18.030 ","End":"05:21.830","Text":"A reaction with a rate constant of 2000 seconds to the power of"},{"Start":"05:21.830 ","End":"05:25.865","Text":"negative 1 will be over in a small fraction of a second,"},{"Start":"05:25.865 ","End":"05:29.300","Text":"because this is so tiny."},{"Start":"05:29.300 ","End":"05:34.205","Text":"This is 1^2000 seconds,"},{"Start":"05:34.205 ","End":"05:42.440","Text":"1/2000 thousand seconds is the actual reaction rate with this constant."},{"Start":"05:42.440 ","End":"05:46.745","Text":"If a reaction rate depends on the concentration of 2 different compounds,"},{"Start":"05:46.745 ","End":"05:49.910","Text":"or if the reaction is between 2 molecules of the same compound,"},{"Start":"05:49.910 ","End":"05:53.600","Text":"the reaction is second-order and K is"},{"Start":"05:53.600 ","End":"05:59.980","Text":"a second-order rate constant with units of m^-1 and S^-1."},{"Start":"05:59.980 ","End":"06:05.585","Text":"Molarity, molar to the negative 1 concentration and substrate."},{"Start":"06:05.585 ","End":"06:10.280","Text":"The rate equation then becomes V velocity equals the rate"},{"Start":"06:10.280 ","End":"06:15.695","Text":"constant times the concentration of substrate 1 and substrate 2,"},{"Start":"06:15.695 ","End":"06:17.585","Text":"negative 1 and negative 2."},{"Start":"06:17.585 ","End":"06:20.315","Text":"From transition state theory,"},{"Start":"06:20.315 ","End":"06:22.250","Text":"we can derive an expression that relates"},{"Start":"06:22.250 ","End":"06:25.340","Text":"the magnitude of a rate constant to the activation energy."},{"Start":"06:25.340 ","End":"06:31.520","Text":"You have the constant equals the constant times the temperature over h and you"},{"Start":"06:31.520 ","End":"06:39.100","Text":"have e log e to the power of a negative Delta G++ over RT."},{"Start":"06:39.100 ","End":"06:46.955","Text":"In this formula, K is the Boltzmann constant and H is Planck\u0027s constant."},{"Start":"06:46.955 ","End":"06:51.080","Text":"The important point here is that the relationship between the rate"},{"Start":"06:51.080 ","End":"06:55.185","Text":"constant K and the activation energy,"},{"Start":"06:55.185 ","End":"06:59.735","Text":"Delta G is inverse and exponential."},{"Start":"06:59.735 ","End":"07:04.135","Text":"Exponential because this is to the power and inverse because it\u0027s negative."},{"Start":"07:04.135 ","End":"07:06.105","Text":"In simplified terms,"},{"Start":"07:06.105 ","End":"07:08.375","Text":"this is the basis for the statement that"},{"Start":"07:08.375 ","End":"07:13.925","Text":"a lower activation energy means a faster reaction rate."},{"Start":"07:13.925 ","End":"07:18.320","Text":"Lower activation energy of Delta G,"},{"Start":"07:18.320 ","End":"07:23.330","Text":"because it\u0027s inverse, means a higher reaction rate,"},{"Start":"07:23.330 ","End":"07:25.175","Text":"a faster reaction rate."},{"Start":"07:25.175 ","End":"07:28.925","Text":"Now we turn from what enzymes do to how they do it."},{"Start":"07:28.925 ","End":"07:33.080","Text":"A few principles explain the catalytic power and specificity of enzymes,"},{"Start":"07:33.080 ","End":"07:38.090","Text":"and this will be what we introduce in the next topic."},{"Start":"07:38.090 ","End":"07:43.370","Text":"We completed reaction rate in thermodynamics and we learned about"},{"Start":"07:43.370 ","End":"07:46.130","Text":"the enzyme reaction equilibrium constant and rate constant"},{"Start":"07:46.130 ","End":"07:49.920","Text":"and enzyme reaction rate equation."}],"ID":30117},{"Watched":false,"Name":"Exercise 11","Duration":"1m 40s","ChapterTopicVideoID":28575,"CourseChapterTopicPlaylistID":286642,"HasSubtitles":true,"ThumbnailPath":null,"UploadDate":null,"DurationForVideoObject":null,"Description":null,"MetaTitle":null,"MetaDescription":null,"Canonical":null,"VideoComments":[],"Subtitles":[{"Start":"00:00.000 ","End":"00:03.180","Text":"We completed a lesson on reaction rates and"},{"Start":"00:03.180 ","End":"00:06.540","Text":"thermodynamics and now we are testing your knowledge with an exercise."},{"Start":"00:06.540 ","End":"00:11.985","Text":"From thermodynamics, the relationship between K\u0027 equilibrium and"},{"Start":"00:11.985 ","End":"00:15.750","Text":"Delta G\u0027 can be described by the expression"},{"Start":"00:15.750 ","End":"00:20.280","Text":"Delta G\u0027 equals negative RT natural log of K\u0027 equilibrium."},{"Start":"00:20.280 ","End":"00:23.849","Text":"Part 1: What do the components of this formula represent?"},{"Start":"00:23.849 ","End":"00:26.970","Text":"Reaction equilibria are linked to the standard free energy change for"},{"Start":"00:26.970 ","End":"00:31.335","Text":"the reaction Delta G. An equilibrium such as"},{"Start":"00:31.335 ","End":"00:34.670","Text":"S substrate and product interconversion is"},{"Start":"00:34.670 ","End":"00:39.450","Text":"described by n equilibrium constant K equilibrium."},{"Start":"00:39.450 ","End":"00:42.935","Text":"Under the standard conditions used to compare biochemical processes,"},{"Start":"00:42.935 ","End":"00:44.360","Text":"the equilibrium constant,"},{"Start":"00:44.360 ","End":"00:50.590","Text":"K equilibrium or for short K is denoted K\u0027 equilibrium or K\u0027 for short."},{"Start":"00:50.590 ","End":"00:52.415","Text":"R in this is the gas constant,"},{"Start":"00:52.415 ","End":"00:55.500","Text":"8.315 joules per mole."},{"Start":"00:55.600 ","End":"00:58.160","Text":"T is the absolute temperature,"},{"Start":"00:58.160 ","End":"01:01.825","Text":"298 Kelvin or 25 degrees Celsius."},{"Start":"01:01.825 ","End":"01:04.000","Text":"You have these."},{"Start":"01:04.000 ","End":"01:08.780","Text":"Part 2: What does this formula signify with regard to enzymatic reactions?"},{"Start":"01:08.780 ","End":"01:10.940","Text":"The equilibrium constant is directly related to"},{"Start":"01:10.940 ","End":"01:13.640","Text":"the overall standard free change for the reaction."},{"Start":"01:13.640 ","End":"01:16.310","Text":"So equilibrium constant N,"},{"Start":"01:16.310 ","End":"01:18.140","Text":"standard free energy change."},{"Start":"01:18.140 ","End":"01:23.990","Text":"A large negative value for Delta G reflects a favorable reaction equilibrium."},{"Start":"01:23.990 ","End":"01:27.530","Text":"The rate is determined by the concentration of the reactant or"},{"Start":"01:27.530 ","End":"01:31.130","Text":"reactants and by a rate constant,"},{"Start":"01:31.130 ","End":"01:39.120","Text":"usually denoted by K. This is relating the rate constant with Delta G."}],"ID":30118},{"Watched":false,"Name":"Exercise 12","Duration":"2m 28s","ChapterTopicVideoID":28576,"CourseChapterTopicPlaylistID":286642,"HasSubtitles":true,"ThumbnailPath":null,"UploadDate":null,"DurationForVideoObject":null,"Description":null,"MetaTitle":null,"MetaDescription":null,"Canonical":null,"VideoComments":[],"Subtitles":[{"Start":"00:00.000 ","End":"00:04.785","Text":"We have another question with regard to the lesson on reaction rate and thermodynamics."},{"Start":"00:04.785 ","End":"00:09.525","Text":"Part I. What is a first-order reaction and what is the expression that represents it?"},{"Start":"00:09.525 ","End":"00:13.410","Text":"A first-order reaction is a reaction in which the rate depends only on"},{"Start":"00:13.410 ","End":"00:17.940","Text":"the concentration of S, of 1 substrate."},{"Start":"00:17.940 ","End":"00:21.600","Text":"For the unimolecular reaction S-P, substrate to product,"},{"Start":"00:21.600 ","End":"00:24.465","Text":"the rate or velocity of the reaction V velocity"},{"Start":"00:24.465 ","End":"00:28.380","Text":"representing the amount of substrate that reacts per unit time is expressed"},{"Start":"00:28.380 ","End":"00:35.505","Text":"by the rate equation formula V=k times the concentration of substrate,"},{"Start":"00:35.505 ","End":"00:39.625","Text":"where k is a constant."},{"Start":"00:39.625 ","End":"00:45.350","Text":"The reaction rate depends only on the concentration of S since this is a constant."},{"Start":"00:45.350 ","End":"00:48.985","Text":"Part II. What does the k signify in the expression mentioned in Part I?"},{"Start":"00:48.985 ","End":"00:52.760","Text":"The factor k is a proportionality constant that reflects the probability of"},{"Start":"00:52.760 ","End":"00:57.049","Text":"reaction under a given set of conditions which includes pH,"},{"Start":"00:57.049 ","End":"00:58.820","Text":"temperature, and so forth."},{"Start":"00:58.820 ","End":"01:05.585","Text":"Here, k is a first-order rate constant and has units of reciprocal times such as s^-1."},{"Start":"01:05.585 ","End":"01:08.505","Text":"S represents second. Part III."},{"Start":"01:08.505 ","End":"01:16.160","Text":"If a first-order reaction has a rate constant of k=0.03s^-1,"},{"Start":"01:16.160 ","End":"01:17.855","Text":"what does this mean?"},{"Start":"01:17.855 ","End":"01:22.985","Text":"This may be interpreted qualitatively from a quality perspective to mean that"},{"Start":"01:22.985 ","End":"01:29.690","Text":"3% of the available substrate will be converted to P in 1 second."},{"Start":"01:29.690 ","End":"01:32.150","Text":"Now, mind you pay attention, this can be confusing."},{"Start":"01:32.150 ","End":"01:38.870","Text":"There\u0027s a small lowercase s here and a uppercase S. This stands for"},{"Start":"01:38.870 ","End":"01:45.905","Text":"substrate and small s stands for seconds,"},{"Start":"01:45.905 ","End":"01:47.165","Text":"a unit of time."},{"Start":"01:47.165 ","End":"01:52.340","Text":"If a first-order reaction has a rate constant k(X)s^-1,"},{"Start":"01:52.340 ","End":"01:59.510","Text":"it means that X% of the available substrate will be converted to product in 1 second."},{"Start":"01:59.510 ","End":"02:04.385","Text":"That\u0027s where we say if we have 0.03,"},{"Start":"02:04.385 ","End":"02:12.890","Text":"it means that 3% will be converted of the substrate into product in 1 second."},{"Start":"02:12.890 ","End":"02:17.510","Text":"A reaction with a rate constant of 2,000s^-1 will be over in"},{"Start":"02:17.510 ","End":"02:22.555","Text":"a small fraction of a second because it\u0027s 1 over 2,000."},{"Start":"02:22.555 ","End":"02:25.350","Text":"That is super-fast. With that,"},{"Start":"02:25.350 ","End":"02:29.380","Text":"we complete another exercise on reaction rates and thermodynamics."}],"ID":30119},{"Watched":false,"Name":"Exercise 13","Duration":"50s","ChapterTopicVideoID":28577,"CourseChapterTopicPlaylistID":286642,"HasSubtitles":true,"ThumbnailPath":null,"UploadDate":null,"DurationForVideoObject":null,"Description":null,"MetaTitle":null,"MetaDescription":null,"Canonical":null,"VideoComments":[],"Subtitles":[{"Start":"00:00.000 ","End":"00:02.475","Text":"Let\u0027s dive into another exercise,"},{"Start":"00:02.475 ","End":"00:05.850","Text":"regarding the lesson on reaction rate and thermodynamics."},{"Start":"00:05.850 ","End":"00:10.965","Text":"What is a second order reaction and how is this expressed in the rate equation formula?"},{"Start":"00:10.965 ","End":"00:14.640","Text":"If a reaction rate depends on the concentration of two different compounds,"},{"Start":"00:14.640 ","End":"00:17.895","Text":"or if the reaction is between molecules of the same compound,"},{"Start":"00:17.895 ","End":"00:21.540","Text":"the reaction is considered second order, and K,"},{"Start":"00:21.540 ","End":"00:24.420","Text":"the constant is a second-order rate constant with"},{"Start":"00:24.420 ","End":"00:27.525","Text":"units of m to the negative 1 and S to the negative 1."},{"Start":"00:27.525 ","End":"00:29.520","Text":"The rate equation then becomes V,"},{"Start":"00:29.520 ","End":"00:31.200","Text":"velocity equals K,"},{"Start":"00:31.200 ","End":"00:34.340","Text":"the constant times the concentration of"},{"Start":"00:34.340 ","End":"00:40.010","Text":"substrate to the power of negative 1 and substrate negative 2."},{"Start":"00:40.010 ","End":"00:44.120","Text":"A second order reaction is one that has"},{"Start":"00:44.120 ","End":"00:46.160","Text":"two different compounds or two molecules of"},{"Start":"00:46.160 ","End":"00:50.400","Text":"the same compound that are part of the reaction."}],"ID":30120}],"Thumbnail":null,"ID":286642},{"Name":"Enzyme Function","TopicPlaylistFirstVideoID":0,"Duration":null,"Videos":[{"Watched":false,"Name":"Enzymes The Catalysts","Duration":"6m 57s","ChapterTopicVideoID":28609,"CourseChapterTopicPlaylistID":286643,"HasSubtitles":true,"ThumbnailPath":null,"UploadDate":null,"DurationForVideoObject":null,"Description":null,"MetaTitle":null,"MetaDescription":null,"Canonical":null,"VideoComments":[],"Subtitles":[{"Start":"00:00.000 ","End":"00:02.685","Text":"Welcome to the topic of enzyme function."},{"Start":"00:02.685 ","End":"00:04.185","Text":"We\u0027re going to start with learning about"},{"Start":"00:04.185 ","End":"00:06.780","Text":"enzymes as a catalyst, and by the end of the section,"},{"Start":"00:06.780 ","End":"00:09.000","Text":"we will be able to talk about enzymes\u0027 role as"},{"Start":"00:09.000 ","End":"00:11.835","Text":"catalyst and how enzymes increase reaction rate."},{"Start":"00:11.835 ","End":"00:14.190","Text":"We touched upon this in the previous topic"},{"Start":"00:14.190 ","End":"00:16.800","Text":"and now we\u0027re going to get into a little more details."},{"Start":"00:16.800 ","End":"00:23.730","Text":"Enzymes are extraordinary catalysts and that is their key function, catalysis."},{"Start":"00:23.730 ","End":"00:29.400","Text":"Enzymes can increase reaction rates by 5-17 orders of magnitude."},{"Start":"00:29.400 ","End":"00:33.395","Text":"Remember, enzymes can have different shapes and substrates,"},{"Start":"00:33.395 ","End":"00:36.680","Text":"or there can be multiple enzymes that use the same substrates"},{"Start":"00:36.680 ","End":"00:40.310","Text":"and have different products as a result of the reactions."},{"Start":"00:40.310 ","End":"00:45.350","Text":"They increase the reaction rate by reducing the energy barrier,"},{"Start":"00:45.350 ","End":"00:47.520","Text":"making a smaller energy barrier."},{"Start":"00:47.520 ","End":"00:51.980","Text":"If this a normal activation energy when you add the enzyme catalysis initiated"},{"Start":"00:51.980 ","End":"00:57.155","Text":"by the enzyme results in smaller activation energy and therefore,"},{"Start":"00:57.155 ","End":"01:00.090","Text":"the reaction occurs at a faster rate."},{"Start":"01:00.090 ","End":"01:05.630","Text":"This can be an increase of reaction rate by 5-17 orders of magnitude."},{"Start":"01:05.630 ","End":"01:08.135","Text":"Enzymes are very specific."},{"Start":"01:08.135 ","End":"01:13.640","Text":"They are readily able to discriminate between substrates with quite similar structures."},{"Start":"01:13.640 ","End":"01:16.940","Text":"Now how are enzymes able to fill this role, this complex,"},{"Start":"01:16.940 ","End":"01:20.360","Text":"massive, and highly selective rate enhancement role?"},{"Start":"01:20.360 ","End":"01:22.400","Text":"What is the source of energy for"},{"Start":"01:22.400 ","End":"01:25.520","Text":"the lowering of the activation energies for specific reactions?"},{"Start":"01:25.520 ","End":"01:28.235","Text":"How do enzymes do what they do?"},{"Start":"01:28.235 ","End":"01:29.945","Text":"How can this be explained?"},{"Start":"01:29.945 ","End":"01:34.940","Text":"How is this dramatic lower of the activation energy done?"},{"Start":"01:34.940 ","End":"01:38.285","Text":"This is what we\u0027re going to delve into in this lesson."},{"Start":"01:38.285 ","End":"01:43.588","Text":"The answer to these questions has 2 distinct but interwoven parts."},{"Start":"01:43.588 ","End":"01:46.655","Text":"1, the first lies in the rearrangements of"},{"Start":"01:46.655 ","End":"01:51.455","Text":"covalent bonds during an enzyme-catalyzed reaction."},{"Start":"01:51.455 ","End":"01:53.900","Text":"Chemical reactions of many types take place between"},{"Start":"01:53.900 ","End":"01:56.960","Text":"substrates and enzymes functional groups,"},{"Start":"01:56.960 ","End":"01:59.000","Text":"specific amino acid side chains,"},{"Start":"01:59.000 ","End":"02:01.190","Text":"metal ions, and co-enzymes."},{"Start":"02:01.190 ","End":"02:05.105","Text":"If you see you have these reactants,"},{"Start":"02:05.105 ","End":"02:06.935","Text":"there is a change."},{"Start":"02:06.935 ","End":"02:12.230","Text":"There can be this rearrangement of covalent bonds between these reactants."},{"Start":"02:12.230 ","End":"02:15.260","Text":"If you see here pink and pink, purple and purple,"},{"Start":"02:15.260 ","End":"02:19.470","Text":"there\u0027s an interaction that changes and then you get purple and pink."},{"Start":"02:19.470 ","End":"02:21.140","Text":"Now if you look at this figure,"},{"Start":"02:21.140 ","End":"02:23.890","Text":"you have the enzyme,"},{"Start":"02:23.890 ","End":"02:29.270","Text":"and the pocket, the active site where the substrate fits into it."},{"Start":"02:29.270 ","End":"02:32.660","Text":"You have many types of chemical reactions that can"},{"Start":"02:32.660 ","End":"02:35.945","Text":"take place between a substrate and the enzyme\u0027s functional groups."},{"Start":"02:35.945 ","End":"02:38.750","Text":"Now, catalytic functional groups may form"},{"Start":"02:38.750 ","End":"02:42.755","Text":"a transient covalent bond with a substrate and activate it for reaction,"},{"Start":"02:42.755 ","End":"02:46.910","Text":"or a group may be transiently transferred from the substrate to the enzyme."},{"Start":"02:46.910 ","End":"02:53.750","Text":"These changes can allow for the changes in the activation energy."},{"Start":"02:53.750 ","End":"02:57.800","Text":"In many cases, these reactions occur only in the enzyme active site,"},{"Start":"02:57.800 ","End":"03:00.425","Text":"in the site where that substrate fits in."},{"Start":"03:00.425 ","End":"03:03.905","Text":"Remember in a previous lesson we talked about how the substrate can be"},{"Start":"03:03.905 ","End":"03:07.550","Text":"sequestered by the enzyme, basically surrounded,"},{"Start":"03:07.550 ","End":"03:11.060","Text":"engulfed in a way that it\u0027s separated from the outside solution so"},{"Start":"03:11.060 ","End":"03:14.660","Text":"there could be basically detachments of bonds with"},{"Start":"03:14.660 ","End":"03:18.260","Text":"the solution or the cell aqueous solution"},{"Start":"03:18.260 ","End":"03:22.790","Text":"and that can allow for the changes in activation energy."},{"Start":"03:22.790 ","End":"03:27.710","Text":"Covalent interactions between enzymes and substrates lower"},{"Start":"03:27.710 ","End":"03:30.770","Text":"the activation energy and thereby accelerate the reaction by"},{"Start":"03:30.770 ","End":"03:34.325","Text":"providing an alternative lower energy reaction path."},{"Start":"03:34.325 ","End":"03:37.520","Text":"Now, the second part of the explanation lies in"},{"Start":"03:37.520 ","End":"03:41.020","Text":"the non-covalent interactions between enzyme and substrate."},{"Start":"03:41.020 ","End":"03:44.480","Text":"Much of the energy required to lower activation energies is"},{"Start":"03:44.480 ","End":"03:47.975","Text":"derived from weak non-covalent interactions between substrate and enzyme."},{"Start":"03:47.975 ","End":"03:51.200","Text":"There can be all these little interactions"},{"Start":"03:51.200 ","End":"03:55.325","Text":"between these residues and the residues of the enzyme."},{"Start":"03:55.325 ","End":"03:58.190","Text":"What really sets enzymes apart from"},{"Start":"03:58.190 ","End":"04:03.770","Text":"most other catalysts is the formation of a specific ES,"},{"Start":"04:03.770 ","End":"04:06.935","Text":"enzyme substrate complex, as seen here."},{"Start":"04:06.935 ","End":"04:11.270","Text":"The interaction between substrate and enzyme in this complex"},{"Start":"04:11.270 ","End":"04:16.145","Text":"is mediated by the same forces that stabilize protein structure,"},{"Start":"04:16.145 ","End":"04:17.690","Text":"including hydrogen bonds,"},{"Start":"04:17.690 ","End":"04:20.515","Text":"and hydrophobic, and ionic interactions."},{"Start":"04:20.515 ","End":"04:24.785","Text":"Now, we covered these in a previous chapter."},{"Start":"04:24.785 ","End":"04:29.160","Text":"Formation of each weak interaction in"},{"Start":"04:29.160 ","End":"04:33.140","Text":"the enzyme-substrate complex is accompanied by release of"},{"Start":"04:33.140 ","End":"04:38.375","Text":"a small amount of the free energy that provides a degree of stability to the interaction."},{"Start":"04:38.375 ","End":"04:42.976","Text":"The energy derived from the enzyme-substrate interaction,"},{"Start":"04:42.976 ","End":"04:47.015","Text":"the ES interaction is called binding energy,"},{"Start":"04:47.015 ","End":"04:50.245","Text":"Delta G subscript B."},{"Start":"04:50.245 ","End":"04:52.220","Text":"Its significance extends beyond"},{"Start":"04:52.220 ","End":"04:55.620","Text":"a simple stabilization of the enzyme substrate interaction."},{"Start":"04:55.620 ","End":"04:57.169","Text":"If you look here,"},{"Start":"04:57.169 ","End":"04:59.690","Text":"you see the difference between catalyzed and"},{"Start":"04:59.690 ","End":"05:03.665","Text":"uncatalyzed is the binding energy, the Delta G_B."},{"Start":"05:03.665 ","End":"05:08.060","Text":"Binding energy is a major source of free energy used"},{"Start":"05:08.060 ","End":"05:12.215","Text":"by enzymes to lower the activation energies of reactions."},{"Start":"05:12.215 ","End":"05:17.365","Text":"This is how it lowers the activation energy from being up here,"},{"Start":"05:17.365 ","End":"05:19.070","Text":"this is the Delta G,"},{"Start":"05:19.070 ","End":"05:25.835","Text":"to down here, this is now the Delta G of the catalyzed reaction,"},{"Start":"05:25.835 ","End":"05:29.275","Text":"and the difference is this binding energy."},{"Start":"05:29.275 ","End":"05:32.690","Text":"2 fundamental and interrelated principles provide"},{"Start":"05:32.690 ","End":"05:37.970","Text":"a general explanation for how enzymes use non-covalent binding energy."},{"Start":"05:37.970 ","End":"05:42.440","Text":"Much of the catalytic power of enzymes is ultimately derived from"},{"Start":"05:42.440 ","End":"05:44.480","Text":"the free energy released in forming"},{"Start":"05:44.480 ","End":"05:48.200","Text":"many weak bonds and interactions between an enzyme and its substrate."},{"Start":"05:48.200 ","End":"05:53.380","Text":"This binding energy contributes to specificity as well as to catalysis."},{"Start":"05:53.380 ","End":"05:57.965","Text":"Weak interactions are optimized in the reaction transition state;"},{"Start":"05:57.965 ","End":"06:02.750","Text":"enzyme active sites are complimentary not to the substrate per se,"},{"Start":"06:02.750 ","End":"06:06.440","Text":"but to the transition states through which substrates"},{"Start":"06:06.440 ","End":"06:10.790","Text":"pass as they are converted to products during an enzymatic reaction."},{"Start":"06:10.790 ","End":"06:14.105","Text":"Remember we had those reaction intermediates."},{"Start":"06:14.105 ","End":"06:19.280","Text":"Now, these themes are critical to an understanding of enzymes and they now become"},{"Start":"06:19.280 ","End":"06:24.515","Text":"our primary focus as we move forward into the following lesson."},{"Start":"06:24.515 ","End":"06:29.810","Text":"Just to re-emphasize, much of the catalytic power of enzymes is derived from"},{"Start":"06:29.810 ","End":"06:31.640","Text":"the free energy released in forming"},{"Start":"06:31.640 ","End":"06:35.915","Text":"many weak bonds and interactions between an enzyme and its substrate,"},{"Start":"06:35.915 ","End":"06:40.705","Text":"and weak interactions are optimized in the reaction transition state,"},{"Start":"06:40.705 ","End":"06:42.950","Text":"enzyme active sites are complimentary to"},{"Start":"06:42.950 ","End":"06:47.075","Text":"the transition states through which substrates pass."},{"Start":"06:47.075 ","End":"06:51.015","Text":"With that, we completed the section on enzymes, the catalyst,"},{"Start":"06:51.015 ","End":"06:57.690","Text":"and we learned about enzymes role as catalysts and how enzymes increase reaction rate."}],"ID":30121},{"Watched":false,"Name":"Exercise 1","Duration":"2m 22s","ChapterTopicVideoID":28610,"CourseChapterTopicPlaylistID":286643,"HasSubtitles":true,"ThumbnailPath":null,"UploadDate":null,"DurationForVideoObject":null,"Description":null,"MetaTitle":null,"MetaDescription":null,"Canonical":null,"VideoComments":[],"Subtitles":[{"Start":"00:00.080 ","End":"00:05.834","Text":"Welcome to Enzymes: The Catalysts, our first exercise."},{"Start":"00:05.834 ","End":"00:09.255","Text":"Enzymes are highly selective rate enhancement catalysts."},{"Start":"00:09.255 ","End":"00:11.310","Text":"Their ability to do this can be explained with"},{"Start":"00:11.310 ","End":"00:14.760","Text":"2 distinct but interwoven parts. What are these?"},{"Start":"00:14.760 ","End":"00:18.165","Text":"Enzymes are highly selective written enhancement catalysts"},{"Start":"00:18.165 ","End":"00:20.060","Text":"of reactions in cells and organisms,"},{"Start":"00:20.060 ","End":"00:24.395","Text":"and the 2 distinct interwoven parts are; 1,"},{"Start":"00:24.395 ","End":"00:27.015","Text":"the first slides in the rearrangement of"},{"Start":"00:27.015 ","End":"00:30.600","Text":"covalent bonds during an enzyme catalyzed reaction."},{"Start":"00:30.600 ","End":"00:32.658","Text":"Chemical reactions of many types take place"},{"Start":"00:32.658 ","End":"00:35.060","Text":"between substrates and enzymes functional groups,"},{"Start":"00:35.060 ","End":"00:36.920","Text":"specific amino acids and side chains,"},{"Start":"00:36.920 ","End":"00:39.005","Text":"metal ions, and coenzymes, etc."},{"Start":"00:39.005 ","End":"00:41.960","Text":"Catalytic functional groups of an enzyme"},{"Start":"00:41.960 ","End":"00:44.900","Text":"may form a transient covalent bond with a substrate and"},{"Start":"00:44.900 ","End":"00:47.750","Text":"activate it for reaction or a group may be"},{"Start":"00:47.750 ","End":"00:51.725","Text":"transiently transferred from the substrate to the enzyme."},{"Start":"00:51.725 ","End":"00:55.940","Text":"Covalent interactions between enzymes and substrates lower the activation energy,"},{"Start":"00:55.940 ","End":"00:58.490","Text":"and thereby accelerate the reaction by providing"},{"Start":"00:58.490 ","End":"01:01.700","Text":"an alternative lower-energy reaction path."},{"Start":"01:01.700 ","End":"01:05.450","Text":"Now the reaction path requires less of an energy investment,"},{"Start":"01:05.450 ","End":"01:11.435","Text":"and therefore it can occur in a more easier fashion with less investment of energy."},{"Start":"01:11.435 ","End":"01:13.820","Text":"Now the second part of the explanation lies in"},{"Start":"01:13.820 ","End":"01:17.150","Text":"the non-covalent interactions between enzyme and substrate."},{"Start":"01:17.150 ","End":"01:20.180","Text":"Much of the energy required to lower activation energies is derived"},{"Start":"01:20.180 ","End":"01:23.765","Text":"from weak non-covalent interactions between substrate and enzyme."},{"Start":"01:23.765 ","End":"01:26.840","Text":"The interaction between substrate and enzyme in the ES;"},{"Start":"01:26.840 ","End":"01:28.040","Text":"the enzyme substrate complex,"},{"Start":"01:28.040 ","End":"01:31.070","Text":"is mediated by hydrogen bonds and hydrophobic and"},{"Start":"01:31.070 ","End":"01:35.650","Text":"ionic interactions which are the same forces that stabilize protein structure."},{"Start":"01:35.650 ","End":"01:39.515","Text":"These we covered in a previous chapter and"},{"Start":"01:39.515 ","End":"01:43.645","Text":"also relate to the enzyme and substrate interaction."},{"Start":"01:43.645 ","End":"01:46.490","Text":"Formation of each weak interaction i s accompanied by release of"},{"Start":"01:46.490 ","End":"01:50.675","Text":"a small amount of free energy that provides a degree of stability to the interaction."},{"Start":"01:50.675 ","End":"01:55.955","Text":"Now, each weak interaction provides a release of a small amount of free energy,"},{"Start":"01:55.955 ","End":"01:57.920","Text":"but if you remember even when we talked about"},{"Start":"01:57.920 ","End":"02:00.500","Text":"stabilization of proteins and protein structure we"},{"Start":"02:00.500 ","End":"02:02.600","Text":"said weak contractions are either weak when you"},{"Start":"02:02.600 ","End":"02:05.210","Text":"take and compile the several weak interactions."},{"Start":"02:05.210 ","End":"02:08.560","Text":"That\u0027s what holds it together and it\u0027s a strong massive force,"},{"Start":"02:08.560 ","End":"02:11.090","Text":"so you have the same concept playing in"},{"Start":"02:11.090 ","End":"02:17.815","Text":"the enzyme substrate interactions allowing for enzymes to be catalysts."},{"Start":"02:17.815 ","End":"02:23.220","Text":"With that, we covered this exercise within Enzymes: The Catalysts."}],"ID":30122},{"Watched":false,"Name":"Exercise 2","Duration":"49s","ChapterTopicVideoID":28611,"CourseChapterTopicPlaylistID":286643,"HasSubtitles":true,"ThumbnailPath":null,"UploadDate":null,"DurationForVideoObject":null,"Description":null,"MetaTitle":null,"MetaDescription":null,"Canonical":null,"VideoComments":[],"Subtitles":[{"Start":"00:00.000 ","End":"00:03.750","Text":"We have another exercise regarding enzymes, the catalysts."},{"Start":"00:03.750 ","End":"00:06.540","Text":"Complete the sentences regarding enzymes."},{"Start":"00:06.540 ","End":"00:09.315","Text":"Enzymes can increase reaction rates by, blank,"},{"Start":"00:09.315 ","End":"00:14.650","Text":"orders of magnitude and are specific such that they effectively differentiate between,"},{"Start":"00:14.650 ","End":"00:16.080","Text":"blank, with similar structures."},{"Start":"00:16.080 ","End":"00:18.570","Text":"We talked about the order of magnitude."},{"Start":"00:18.570 ","End":"00:21.439","Text":"We mentioned specific numbers and this is,"},{"Start":"00:21.439 ","End":"00:29.205","Text":"enzymes can increase reaction rates by 5-17 orders of magnitude, that is significant."},{"Start":"00:29.205 ","End":"00:33.510","Text":"They are specific enzymes such that they effectively"},{"Start":"00:33.510 ","End":"00:37.665","Text":"differentiate between something with similar structures."},{"Start":"00:37.665 ","End":"00:41.309","Text":"We talked about enzymes and their substrates,"},{"Start":"00:41.309 ","End":"00:46.010","Text":"so they can effectively differentiate between substrates with similar structures,"},{"Start":"00:46.010 ","End":"00:49.380","Text":"and this is their specificity."}],"ID":30123},{"Watched":false,"Name":"Enzymes Part 1","Duration":"9m 22s","ChapterTopicVideoID":28612,"CourseChapterTopicPlaylistID":286643,"HasSubtitles":true,"ThumbnailPath":null,"UploadDate":null,"DurationForVideoObject":null,"Description":null,"MetaTitle":null,"MetaDescription":null,"Canonical":null,"VideoComments":[],"Subtitles":[{"Start":"00:00.000 ","End":"00:04.440","Text":"We were then in the chapter on enzymes and within the topic of enzyme function."},{"Start":"00:04.440 ","End":"00:08.475","Text":"Now, we\u0027re going to do an overview on enzymes."},{"Start":"00:08.475 ","End":"00:09.660","Text":"By the end of this section,"},{"Start":"00:09.660 ","End":"00:12.690","Text":"you\u0027ll be able to describe the role of enzymes and metabolic pathways,"},{"Start":"00:12.690 ","End":"00:15.215","Text":"explain how enzymes function as molecular catalysts,"},{"Start":"00:15.215 ","End":"00:18.920","Text":"and discuss enzyme regulation by various factors."},{"Start":"00:18.920 ","End":"00:22.235","Text":"Now, we will split this lecture into 3 parts."},{"Start":"00:22.235 ","End":"00:26.000","Text":"In part 1 we will specifically talk about how enzymes function as"},{"Start":"00:26.000 ","End":"00:31.850","Text":"molecular catalysts and define key terms associated with enzymes. Let\u0027s dive in."},{"Start":"00:31.850 ","End":"00:35.270","Text":"Enzymes are catalysts of chemical reactions."},{"Start":"00:35.270 ","End":"00:38.465","Text":"Almost all enzymes are proteins."},{"Start":"00:38.465 ","End":"00:43.468","Text":"The enzyme binds to the reactant molecule or molecules,"},{"Start":"00:43.468 ","End":"00:47.585","Text":"and breaks or forms chemical bonds more readily."},{"Start":"00:47.585 ","End":"00:51.310","Text":"You have the enzyme and the substrate,"},{"Start":"00:51.310 ","End":"00:55.160","Text":"the reactant molecule, and these bind together."},{"Start":"00:55.160 ","End":"00:57.440","Text":"The way they do this is not by"},{"Start":"00:57.440 ","End":"01:02.800","Text":"changing the actual nature of the reaction if it\u0027s exergonic or endergonic."},{"Start":"01:02.800 ","End":"01:09.350","Text":"They do this by reducing the activation energies of the chemical reactions."},{"Start":"01:09.350 ","End":"01:15.455","Text":"If we look at the figure talking about the nature, this isn\u0027t changed."},{"Start":"01:15.455 ","End":"01:18.185","Text":"Delta G isn\u0027t changed."},{"Start":"01:18.185 ","End":"01:22.390","Text":"This change from the reactant to the product stays the same,"},{"Start":"01:22.390 ","End":"01:26.300","Text":"but what changes is the activation energy."},{"Start":"01:26.300 ","End":"01:27.500","Text":"This is reduced."},{"Start":"01:27.500 ","End":"01:31.835","Text":"You have the black activation energy without enzyme."},{"Start":"01:31.835 ","End":"01:37.080","Text":"This is higher, the distance if we look at the y-axis,"},{"Start":"01:37.080 ","End":"01:39.204","Text":"this is our y-axis."},{"Start":"01:39.204 ","End":"01:40.780","Text":"If it was numbered,"},{"Start":"01:40.780 ","End":"01:45.805","Text":"this is higher than the activation energy with enzyme."},{"Start":"01:45.805 ","End":"01:47.380","Text":"Yet the Delta G,"},{"Start":"01:47.380 ","End":"01:52.975","Text":"the change of energy between the reactant to the product or product to reactant,"},{"Start":"01:52.975 ","End":"01:58.100","Text":"meaning exergonic versus endergonic, that hasn\u0027t changed."},{"Start":"01:58.250 ","End":"02:01.235","Text":"We can think of a boulder,"},{"Start":"02:01.235 ","End":"02:03.340","Text":"if we have a boulder,"},{"Start":"02:03.340 ","End":"02:05.110","Text":"we just had to roll down the hill,"},{"Start":"02:05.110 ","End":"02:06.650","Text":"there would be no problem. You would nudge it."},{"Start":"02:06.650 ","End":"02:07.750","Text":"If this was the hill,"},{"Start":"02:07.750 ","End":"02:11.559","Text":"it would just roll down or if it was up here,"},{"Start":"02:11.559 ","End":"02:16.405","Text":"you give it a nudge, it would just roll down."},{"Start":"02:16.405 ","End":"02:23.540","Text":"It has a higher or if we say right here the same height of this,"},{"Start":"02:23.540 ","End":"02:29.419","Text":"it has a higher energy than the product."},{"Start":"02:29.419 ","End":"02:31.414","Text":"Let\u0027s say the boulder is our reactant,"},{"Start":"02:31.414 ","End":"02:33.980","Text":"the energy is higher than the product."},{"Start":"02:33.980 ","End":"02:39.050","Text":"Anything that goes from high energy to low energy is preferred,"},{"Start":"02:39.050 ","End":"02:42.060","Text":"is a reaction that is favored."},{"Start":"02:42.060 ","End":"02:44.960","Text":"The balls hitting here, will just roll down and it would"},{"Start":"02:44.960 ","End":"02:48.605","Text":"lose energy as it rolls down by kinetic energy."},{"Start":"02:48.605 ","End":"02:52.400","Text":"Therefore at the end would have lower energy on its own"},{"Start":"02:52.400 ","End":"02:57.335","Text":"because kinetic energy was lost to the system."},{"Start":"02:57.335 ","End":"03:00.500","Text":"Yet, when the ball is hitting here,"},{"Start":"03:00.500 ","End":"03:05.420","Text":"it has to get through this hill before it can roll down,"},{"Start":"03:05.420 ","End":"03:11.360","Text":"which means we need to invest energy in pushing it up the hill before it reaches the top."},{"Start":"03:11.360 ","End":"03:15.440","Text":"If you think of this boulder and you yourself, this rock,"},{"Start":"03:15.440 ","End":"03:19.009","Text":"this ball, you\u0027re trying to push this rock or this ball up the hill,"},{"Start":"03:19.009 ","End":"03:20.270","Text":"it\u0027s going to be hard work."},{"Start":"03:20.270 ","End":"03:24.190","Text":"You are going to invest energy to do this."},{"Start":"03:24.190 ","End":"03:26.225","Text":"You have to push it up."},{"Start":"03:26.225 ","End":"03:28.550","Text":"Now if you had to push it up all the way here,"},{"Start":"03:28.550 ","End":"03:32.570","Text":"you\u0027d have to invest more energy than if you had to invest,"},{"Start":"03:32.570 ","End":"03:35.900","Text":"if you just had to push it up to this part."},{"Start":"03:35.900 ","End":"03:42.415","Text":"You\u0027d invest more energy pushing it up here than if you pushed it up here."},{"Start":"03:42.415 ","End":"03:45.110","Text":"This is what changes,"},{"Start":"03:45.110 ","End":"03:47.600","Text":"the height of the activation energy,"},{"Start":"03:47.600 ","End":"03:53.810","Text":"the amount of free energy needed to invest in getting the boulder,"},{"Start":"03:53.810 ","End":"03:56.660","Text":"the ball, the reaction to the top of"},{"Start":"03:56.660 ","End":"04:00.565","Text":"the activation energy so that the reaction can occur."},{"Start":"04:00.565 ","End":"04:05.435","Text":"Now, the Delta G in yellow here doesn\u0027t change with the enzyme."},{"Start":"04:05.435 ","End":"04:12.200","Text":"It is the difference in free energy between the reactants state and the product state."},{"Start":"04:12.200 ","End":"04:14.635","Text":"The product is now here."},{"Start":"04:14.635 ","End":"04:18.710","Text":"This doesn\u0027t change it\u0027s the same both with an enzyme and without"},{"Start":"04:18.710 ","End":"04:22.610","Text":"an enzyme because it\u0027s the difference between this and this."},{"Start":"04:22.610 ","End":"04:25.639","Text":"Yet when looking at the activation energy,"},{"Start":"04:25.639 ","End":"04:29.735","Text":"you see activation energy is EA."},{"Start":"04:29.735 ","End":"04:31.910","Text":"This is different with, and without the enzymes."},{"Start":"04:31.910 ","End":"04:33.770","Text":"Again, the black is the energy investment"},{"Start":"04:33.770 ","End":"04:37.040","Text":"needed in order for the reaction to occur without"},{"Start":"04:37.040 ","End":"04:42.725","Text":"an enzyme and the red is when the activation energy is with an enzyme,"},{"Start":"04:42.725 ","End":"04:44.660","Text":"it is lower than that."},{"Start":"04:44.660 ","End":"04:47.750","Text":"The hill is lower when the enzyme is added,"},{"Start":"04:47.750 ","End":"04:50.200","Text":"so a smaller investment of energy is needed."},{"Start":"04:50.200 ","End":"04:53.140","Text":"Let\u0027s see how enzymes do this."},{"Start":"04:53.140 ","End":"04:56.990","Text":"Enzymes have an active site and substrate"},{"Start":"04:56.990 ","End":"05:00.320","Text":"specificity so that they correspond to each other."},{"Start":"05:00.320 ","End":"05:07.215","Text":"These 2 pieces of the puzzle fit very specifically together."},{"Start":"05:07.215 ","End":"05:14.060","Text":"An enzyme binds to a chemical reactant or reactants generally named as substrate."},{"Start":"05:14.060 ","End":"05:18.455","Text":"In some reactions, a single reactant substrate breaks down into multiple products."},{"Start":"05:18.455 ","End":"05:20.540","Text":"You have 1 substrate,"},{"Start":"05:20.540 ","End":"05:24.140","Text":"1 single reactant that breaks in 2 multiple products."},{"Start":"05:24.140 ","End":"05:25.850","Text":"You now have 2 products."},{"Start":"05:25.850 ","End":"05:32.060","Text":"In other cases, you have 2 substrates that may come together to create 1 larger molecule."},{"Start":"05:32.060 ","End":"05:35.960","Text":"Here we have 2 substrates that come together to"},{"Start":"05:35.960 ","End":"05:40.880","Text":"create 1 large product, 1 larger molecule."},{"Start":"05:40.880 ","End":"05:44.225","Text":"The active site, as seen here,"},{"Start":"05:44.225 ","End":"05:48.065","Text":"the active site of the enzyme is"},{"Start":"05:48.065 ","End":"05:52.220","Text":"the location within the enzyme where the substrate binds the enzyme."},{"Start":"05:52.220 ","End":"05:55.820","Text":"It has a specific arrangement,"},{"Start":"05:55.820 ","End":"06:02.165","Text":"conformation, and environment that is particularly fitting for the substrate."},{"Start":"06:02.165 ","End":"06:10.145","Text":"Specificity means that there\u0027s a specifically matched enzyme for each substrate."},{"Start":"06:10.145 ","End":"06:12.470","Text":"However, there is flexibility as well."},{"Start":"06:12.470 ","End":"06:18.920","Text":"You have the same site and you have these 2 substrates that can come together and fit,"},{"Start":"06:18.920 ","End":"06:21.440","Text":"or you have this 1 substrate that comes together and fit."},{"Start":"06:21.440 ","End":"06:22.610","Text":"This is just an example."},{"Start":"06:22.610 ","End":"06:25.415","Text":"This is not actually how it happened 2 substrates versus 1."},{"Start":"06:25.415 ","End":"06:31.595","Text":"The idea is that there\u0027s flexibility in this specificity between enzyme and substrate."},{"Start":"06:31.595 ","End":"06:37.138","Text":"It may mean that an enzyme can bind to 2 different substrates,"},{"Start":"06:37.138 ","End":"06:40.055","Text":"and have 2 different reactions occur."},{"Start":"06:40.055 ","End":"06:44.060","Text":"Now, enzymes are suited to function best within"},{"Start":"06:44.060 ","End":"06:48.330","Text":"a certain pH and temperature range very specific."},{"Start":"06:48.330 ","End":"06:53.809","Text":"The idea again is with the specificity because the different environments require,"},{"Start":"06:53.809 ","End":"06:57.060","Text":"and different reactions require specific pH and temperature."},{"Start":"06:57.060 ","End":"06:58.130","Text":"If we look at this figure,"},{"Start":"06:58.130 ","End":"06:59.450","Text":"we\u0027d seen this figure before,"},{"Start":"06:59.450 ","End":"07:01.550","Text":"you have 3 examples of enzymes,"},{"Start":"07:01.550 ","End":"07:03.860","Text":"pepsin, trypsin, and alkaline phosphates."},{"Start":"07:03.860 ","End":"07:09.710","Text":"These enzymes react and function in different environments to"},{"Start":"07:09.710 ","End":"07:12.380","Text":"result in different products that are needed in"},{"Start":"07:12.380 ","End":"07:16.040","Text":"the specific environments they\u0027re at on specific conditions."},{"Start":"07:16.040 ","End":"07:17.765","Text":"If we look at pepsin,"},{"Start":"07:17.765 ","End":"07:20.960","Text":"you have y-axis is percent maximum activity,"},{"Start":"07:20.960 ","End":"07:24.035","Text":"100 percent maximum activity of pepsin,"},{"Start":"07:24.035 ","End":"07:26.855","Text":"100 percent activity is seen here,"},{"Start":"07:26.855 ","End":"07:28.700","Text":"is a little bit below pH of 2,"},{"Start":"07:28.700 ","End":"07:30.710","Text":"meaning it works in an acidic environment."},{"Start":"07:30.710 ","End":"07:32.345","Text":"That\u0027s where pepsin works best."},{"Start":"07:32.345 ","End":"07:34.940","Text":"On the other hand, you have alkaline phosphatase."},{"Start":"07:34.940 ","End":"07:38.540","Text":"It\u0027s 100 percent activity,"},{"Start":"07:38.540 ","End":"07:42.480","Text":"is at little below 9,"},{"Start":"07:42.480 ","End":"07:46.615","Text":"meaning it\u0027s at a basic pH."},{"Start":"07:46.615 ","End":"07:49.790","Text":"This is where alkaline phosphatase works best."},{"Start":"07:49.790 ","End":"07:53.125","Text":"The 3rd example is of trypsin."},{"Start":"07:53.125 ","End":"07:58.425","Text":"Trypsin you have the 100 percent activity at a little below 7."},{"Start":"07:58.425 ","End":"08:00.810","Text":"It\u0027s about at neutral pH."},{"Start":"08:00.810 ","End":"08:02.390","Text":"If we think about neutral pH,"},{"Start":"08:02.390 ","End":"08:04.205","Text":"like you see that in the blood or whatever,"},{"Start":"08:04.205 ","End":"08:13.925","Text":"you have these enzymes that have evolved to function and carry out catalyzed reactions in"},{"Start":"08:13.925 ","End":"08:19.010","Text":"the environments where they are needed and therefore they are suited to function best"},{"Start":"08:19.010 ","End":"08:24.420","Text":"within that specific environment, within those conditions."},{"Start":"08:24.420 ","End":"08:27.555","Text":"That means specific pH and temperature."},{"Start":"08:27.555 ","End":"08:32.255","Text":"There\u0027s a range because if we look at trypsin,"},{"Start":"08:32.255 ","End":"08:39.980","Text":"it functions between pH of 2 and pH of 9.5."},{"Start":"08:39.980 ","End":"08:44.945","Text":"It doesn\u0027t function ideally in optimally this entire range."},{"Start":"08:44.945 ","End":"08:51.635","Text":"It is more optimal probably in the range of 5-7.5,"},{"Start":"08:51.635 ","End":"08:54.890","Text":"but there is this range that"},{"Start":"08:54.890 ","End":"08:57.950","Text":"it functions in and you can say the same for each 1 of these."},{"Start":"08:57.950 ","End":"09:00.020","Text":"You could say the same for trypsin,"},{"Start":"09:00.020 ","End":"09:04.825","Text":"and you can say the same for alkaline phosphatase and pepsin and every enzyme."},{"Start":"09:04.825 ","End":"09:08.690","Text":"With this, we completed part 1 of the overview on"},{"Start":"09:08.690 ","End":"09:12.845","Text":"enzymes and we explained how enzymes function as molecular catalysts,"},{"Start":"09:12.845 ","End":"09:17.595","Text":"introduced these ideas, we\u0027ll talk about them more in the next parts."},{"Start":"09:17.595 ","End":"09:22.019","Text":"We defined key terms associated with enzymes."}],"ID":30124},{"Watched":false,"Name":"Enzymes Part 2","Duration":"9m 52s","ChapterTopicVideoID":28613,"CourseChapterTopicPlaylistID":286643,"HasSubtitles":true,"ThumbnailPath":null,"UploadDate":null,"DurationForVideoObject":null,"Description":null,"MetaTitle":null,"MetaDescription":null,"Canonical":null,"VideoComments":[],"Subtitles":[{"Start":"00:00.470 ","End":"00:03.405","Text":"Welcome to part 2,"},{"Start":"00:03.405 ","End":"00:07.050","Text":"an overview of enzymes within enzyme function."},{"Start":"00:07.050 ","End":"00:10.920","Text":"By the end of this part you will be able to describe"},{"Start":"00:10.920 ","End":"00:13.260","Text":"different models of enzyme function and"},{"Start":"00:13.260 ","End":"00:15.780","Text":"describe the role of enzymes in metabolic pathways."},{"Start":"00:15.780 ","End":"00:17.595","Text":"Now, let\u0027s go over enzyme function."},{"Start":"00:17.595 ","End":"00:18.960","Text":"There are 2 main models."},{"Start":"00:18.960 ","End":"00:22.980","Text":"You have a lock and key model in which an enzyme and substrate fits"},{"Start":"00:22.980 ","End":"00:27.383","Text":"together perfectly in one instantaneous step as seen in the figure."},{"Start":"00:27.383 ","End":"00:30.760","Text":"You have the substrate, you have the active site of the enzyme,"},{"Start":"00:30.760 ","End":"00:36.018","Text":"they look like 2 pieces of a puzzle that fit together perfectly and they do."},{"Start":"00:36.018 ","End":"00:37.770","Text":"They just come together and you have"},{"Start":"00:37.770 ","End":"00:42.000","Text":"the enzyme substrate complex to result in the desired product."},{"Start":"00:42.000 ","End":"00:48.500","Text":"But, there\u0027s also the induced fit model in which enzyme and substrate"},{"Start":"00:48.500 ","End":"00:51.200","Text":"interaction causes slight shift in"},{"Start":"00:51.200 ","End":"00:53.870","Text":"the enzyme structure so that it"},{"Start":"00:53.870 ","End":"00:56.750","Text":"confirms an ideal binding arrangement between the enzyme,"},{"Start":"00:56.750 ","End":"00:58.700","Text":"and the substrates transition state."},{"Start":"00:58.700 ","End":"01:01.670","Text":"If you look here, the substrate doesn\u0027t fit"},{"Start":"01:01.670 ","End":"01:05.180","Text":"exactly the enzyme\u0027s active site because the enzyme\u0027s active site,"},{"Start":"01:05.180 ","End":"01:09.865","Text":"if we number this 1 and this 3,"},{"Start":"01:09.865 ","End":"01:11.360","Text":"and this 2,"},{"Start":"01:11.360 ","End":"01:12.890","Text":"you see this is square here,"},{"Start":"01:12.890 ","End":"01:14.330","Text":"but this is round."},{"Start":"01:14.330 ","End":"01:16.400","Text":"You see this is triangular here,"},{"Start":"01:16.400 ","End":"01:19.430","Text":"but this is a little bit of a rounded shape as well."},{"Start":"01:19.430 ","End":"01:22.430","Text":"You see this is round while this is square."},{"Start":"01:22.430 ","End":"01:23.990","Text":"It doesn\u0027t fit."},{"Start":"01:23.990 ","End":"01:25.820","Text":"But, as it gets close together,"},{"Start":"01:25.820 ","End":"01:29.315","Text":"and the residues start interacting with each other,"},{"Start":"01:29.315 ","End":"01:36.110","Text":"the enzyme\u0027s active site rearranges so that now the 2 pieces,"},{"Start":"01:36.110 ","End":"01:39.320","Text":"the enzyme and substrate that didn\u0027t fit together perfectly,"},{"Start":"01:39.320 ","End":"01:41.870","Text":"as they connect now the structure changed so"},{"Start":"01:41.870 ","End":"01:45.035","Text":"that they end up fitting each other perfectly."},{"Start":"01:45.035 ","End":"01:48.560","Text":"This is the induced fit model."},{"Start":"01:48.560 ","End":"01:54.485","Text":"The ideal binding maximizes the enzyme\u0027s ability to catalyze its reaction."},{"Start":"01:54.485 ","End":"02:01.265","Text":"This ideal binding result in optimal catalysis of the reaction."},{"Start":"02:01.265 ","End":"02:04.295","Text":"How do the enzymes promote chemical reactions?"},{"Start":"02:04.295 ","End":"02:09.425","Text":"They do this by bringing the substrates together in an optimal orientation."},{"Start":"02:09.425 ","End":"02:11.090","Text":"If we look here, for example,"},{"Start":"02:11.090 ","End":"02:13.080","Text":"we have a glucose and a fructose."},{"Start":"02:13.080 ","End":"02:19.730","Text":"In order for them to interact and bind in a reaction and form sucrose,"},{"Start":"02:19.730 ","End":"02:23.690","Text":"they need to actually form a glycosidic bond,"},{"Start":"02:23.690 ","End":"02:26.750","Text":"which results by releasing of a water molecule."},{"Start":"02:26.750 ","End":"02:27.905","Text":"How this is done,"},{"Start":"02:27.905 ","End":"02:29.450","Text":"you have an oxygen and"},{"Start":"02:29.450 ","End":"02:33.770","Text":"a hydrogen of one of these that\u0027s released because you have 2 of them."},{"Start":"02:33.770 ","End":"02:37.630","Text":"You have 1 oxygen hydrogen here and 1 oxygen and hydrogen here,"},{"Start":"02:37.630 ","End":"02:39.055","Text":"so there\u0027s 2 altogether."},{"Start":"02:39.055 ","End":"02:40.480","Text":"You have one of these being released."},{"Start":"02:40.480 ","End":"02:45.763","Text":"Let\u0027s just say that this one is released and you have the hydrogen here released,"},{"Start":"02:45.763 ","End":"02:48.035","Text":"so now 2 hydrogen and oxygen,"},{"Start":"02:48.035 ","End":"02:50.570","Text":"which in essence is a water molecule."},{"Start":"02:50.570 ","End":"02:52.255","Text":"This is released."},{"Start":"02:52.255 ","End":"02:59.840","Text":"This happens so that now this oxygen can bind directly to this carbon."},{"Start":"02:59.840 ","End":"03:02.450","Text":"Because this carbon lost this oxygen, hydrogen,"},{"Start":"03:02.450 ","End":"03:08.900","Text":"and you have now these 2 carbons are connected via 1 oxygen molecule,"},{"Start":"03:08.900 ","End":"03:11.345","Text":"and this is the glycosidic bond."},{"Start":"03:11.345 ","End":"03:14.353","Text":"For this to occur between the glucose,"},{"Start":"03:14.353 ","End":"03:17.090","Text":"and the fructose to form the sucrose,"},{"Start":"03:17.090 ","End":"03:22.562","Text":"you need these substrates to be brought together in this optimal orientation."},{"Start":"03:22.562 ","End":"03:29.070","Text":"You need the carbon 1 of glucose and the carbon 2 of"},{"Start":"03:29.070 ","End":"03:35.705","Text":"the fructose brought together into proximity so this can happen."},{"Start":"03:35.705 ","End":"03:39.185","Text":"Another way that the enzyme promotes a chemical reaction is by creating"},{"Start":"03:39.185 ","End":"03:43.745","Text":"an optimal environment within the active site for the reaction to occur."},{"Start":"03:43.745 ","End":"03:45.440","Text":"The active site of this enzyme,"},{"Start":"03:45.440 ","End":"03:50.765","Text":"the pocket where the substrate fits in will have the appropriate environment."},{"Start":"03:50.765 ","End":"03:55.280","Text":"For example, for the reaction to occur we need a hydrophobic environment."},{"Start":"03:55.280 ","End":"03:59.525","Text":"This active site, this pocket where the substrate fits"},{"Start":"03:59.525 ","End":"04:05.480","Text":"sequesters the substrate from the cellular environment on the outside,"},{"Start":"04:05.480 ","End":"04:08.390","Text":"which is aqueous and has waters,"},{"Start":"04:08.390 ","End":"04:10.639","Text":"and this hydrophobic environment,"},{"Start":"04:10.639 ","End":"04:15.830","Text":"this hydrophobic molecule is hidden within this active site"},{"Start":"04:15.830 ","End":"04:17.900","Text":"sequestered so it doesn\u0027t interact with"},{"Start":"04:17.900 ","End":"04:22.050","Text":"the hydrophilic environment on that cell around it."},{"Start":"04:22.050 ","End":"04:25.190","Text":"The active site will likely have residues that are"},{"Start":"04:25.190 ","End":"04:28.310","Text":"hydrophobic so that this can interact with"},{"Start":"04:28.310 ","End":"04:32.945","Text":"the hydrophobic substrate in the hydrophobic environment"},{"Start":"04:32.945 ","End":"04:38.120","Text":"for the chemical reaction to proceed in an optimal, most efficient way."},{"Start":"04:38.120 ","End":"04:42.995","Text":"Now, this can also be an ionic environment."},{"Start":"04:42.995 ","End":"04:48.440","Text":"Any other type of environment that is required for the reaction to occur the enzyme"},{"Start":"04:48.440 ","End":"04:50.800","Text":"will provide that for"},{"Start":"04:50.800 ","End":"04:54.515","Text":"the substrate by having specific residues that are appropriate for it."},{"Start":"04:54.515 ","End":"05:00.050","Text":"Now, sometimes the enzyme itself takes part in the chemical reaction itself,"},{"Start":"05:00.050 ","End":"05:02.540","Text":"meaning the substrate atoms bind to the enzyme atoms"},{"Start":"05:02.540 ","End":"05:05.704","Text":"itself and this is part of the reaction."},{"Start":"05:05.704 ","End":"05:12.440","Text":"Now, a key point is that enzymes ultimately remain unchanged by"},{"Start":"05:12.440 ","End":"05:15.590","Text":"the reactions they catalyze so that at"},{"Start":"05:15.590 ","End":"05:19.280","Text":"the end of the reaction the substrate is released,"},{"Start":"05:19.280 ","End":"05:22.145","Text":"and the enzyme is free to repeat the reaction."},{"Start":"05:22.145 ","End":"05:23.990","Text":"You have this enzyme,"},{"Start":"05:23.990 ","End":"05:26.083","Text":"you have enzyme substrate complex,"},{"Start":"05:26.083 ","End":"05:27.410","Text":"you have a reaction occurring,"},{"Start":"05:27.410 ","End":"05:28.505","Text":"the product is released,"},{"Start":"05:28.505 ","End":"05:31.055","Text":"and you now can have"},{"Start":"05:31.055 ","End":"05:35.405","Text":"the same enzyme with the same structure binds to the substrate again,"},{"Start":"05:35.405 ","End":"05:39.493","Text":"or basically have the substrate come and bind to this enzyme,"},{"Start":"05:39.493 ","End":"05:42.815","Text":"and the reaction recycles and repeats itself."},{"Start":"05:42.815 ","End":"05:46.745","Text":"The enzyme basically is recycled and can"},{"Start":"05:46.745 ","End":"05:51.290","Text":"catalyze reaction over and over again as much as is needed."},{"Start":"05:51.290 ","End":"05:57.949","Text":"Evolution resulted in enzymes functioning best within a certain environment,"},{"Start":"05:57.949 ","End":"06:00.200","Text":"within a certain pH and temperature range,"},{"Start":"06:00.200 ","End":"06:02.090","Text":"and we touched upon this before,"},{"Start":"06:02.090 ","End":"06:06.365","Text":"that corresponds to the optimal environment for the reaction to occur."},{"Start":"06:06.365 ","End":"06:09.620","Text":"Metabolism is controlled through"},{"Start":"06:09.620 ","End":"06:13.629","Text":"enzyme regulation and enzymes are regulated by the cells."},{"Start":"06:13.629 ","End":"06:16.190","Text":"Cells control enzyme activity and determine the rates at"},{"Start":"06:16.190 ","End":"06:19.595","Text":"which various biochemical reactions will occur."},{"Start":"06:19.595 ","End":"06:21.380","Text":"How do cells do this?"},{"Start":"06:21.380 ","End":"06:22.805","Text":"Let\u0027s talk about this."},{"Start":"06:22.805 ","End":"06:28.535","Text":"Enzymes can be regulated in ways that either promote or reduce their activity."},{"Start":"06:28.535 ","End":"06:32.030","Text":"There are competitive inhibitors within a cell"},{"Start":"06:32.030 ","End":"06:35.360","Text":"that bind to the active site of an enzyme competing with"},{"Start":"06:35.360 ","End":"06:38.570","Text":"the substrate and in this way as seen in"},{"Start":"06:38.570 ","End":"06:41.915","Text":"the figure you have the active site and the competitive inhibitor,"},{"Start":"06:41.915 ","End":"06:44.750","Text":"it binds to the active site so that now"},{"Start":"06:44.750 ","End":"06:47.780","Text":"the substrate can\u0027t bind to"},{"Start":"06:47.780 ","End":"06:51.335","Text":"the active site because it\u0027s blocked by this competitive inhibitor."},{"Start":"06:51.335 ","End":"06:55.220","Text":"If we have this competitive inhibitor as seen here,"},{"Start":"06:55.220 ","End":"06:59.735","Text":"now it\u0027s blocking the substrate from binding to the active site."},{"Start":"06:59.735 ","End":"07:04.220","Text":"Competitive inhibition is done by competitive inhibitors,"},{"Start":"07:04.220 ","End":"07:07.070","Text":"and in this way it blocks the substrate from binding to the enzyme,"},{"Start":"07:07.070 ","End":"07:09.710","Text":"and thus results in competitive inhibition therefore,"},{"Start":"07:09.710 ","End":"07:11.825","Text":"inhibition of the reaction from occurring."},{"Start":"07:11.825 ","End":"07:14.540","Text":"Alternatively, the opposite of that is"},{"Start":"07:14.540 ","End":"07:18.545","Text":"noncompetitive inhibition by noncompetitive inhibitors."},{"Start":"07:18.545 ","End":"07:21.800","Text":"These bind to another part of an enzyme,"},{"Start":"07:21.800 ","End":"07:27.740","Text":"the allosteric site causing the enzyme to change shape and"},{"Start":"07:27.740 ","End":"07:30.815","Text":"making the active site less effective"},{"Start":"07:30.815 ","End":"07:34.580","Text":"so that the substrate doesn\u0027t bind to the enzyme active site."},{"Start":"07:34.580 ","End":"07:37.115","Text":"If we look here you have active site."},{"Start":"07:37.115 ","End":"07:42.710","Text":"Whereas with competitive inhibitors we saw that there\u0027s a substrate that"},{"Start":"07:42.710 ","End":"07:48.605","Text":"binds here and blocks in a competitive way the substrate from binding."},{"Start":"07:48.605 ","End":"07:53.750","Text":"Why is it competitive? Because it competes with the substrate for the same site."},{"Start":"07:53.750 ","End":"07:58.070","Text":"Competitive inhibitor competes with the substrate because if it"},{"Start":"07:58.070 ","End":"08:02.300","Text":"reaches the active site first it blocks the substrate."},{"Start":"08:02.300 ","End":"08:05.210","Text":"But if the substrate is faster and"},{"Start":"08:05.210 ","End":"08:08.900","Text":"reaches the active site first then the reaction will occur."},{"Start":"08:08.900 ","End":"08:10.490","Text":"Therefore, it\u0027s competitive inhibition."},{"Start":"08:10.490 ","End":"08:12.335","Text":"It\u0027s whoever reaches first."},{"Start":"08:12.335 ","End":"08:13.685","Text":"On the other hand,"},{"Start":"08:13.685 ","End":"08:16.684","Text":"if you have noncompetitive inhibitors,"},{"Start":"08:16.684 ","End":"08:18.950","Text":"they bind in a different site."},{"Start":"08:18.950 ","End":"08:24.245","Text":"They bind in an allosteric site and it results in"},{"Start":"08:24.245 ","End":"08:30.785","Text":"the enzyme having a change in its shape so that the active site is less effective,"},{"Start":"08:30.785 ","End":"08:33.740","Text":"meaning that even if there is a substance that\u0027s bound"},{"Start":"08:33.740 ","End":"08:36.980","Text":"here already and you have this non-competitive inhibitor,"},{"Start":"08:36.980 ","End":"08:39.455","Text":"it isn\u0027t competing for the same site,"},{"Start":"08:39.455 ","End":"08:45.064","Text":"but it\u0027s changing its form so that now they aren\u0027t bound to each other optimally."},{"Start":"08:45.064 ","End":"08:49.460","Text":"Therefore, the reaction doesn\u0027t occur in an optimal and efficient way."},{"Start":"08:49.460 ","End":"08:51.050","Text":"You have competitive inhibitors,"},{"Start":"08:51.050 ","End":"08:55.025","Text":"they do competitive inhibition and non-competitive inhibitors that"},{"Start":"08:55.025 ","End":"09:00.080","Text":"are non-competitive inhibition by binding an allosteric site."},{"Start":"09:00.080 ","End":"09:02.450","Text":"A competitive inhibitor binds"},{"Start":"09:02.450 ","End":"09:06.530","Text":"the active site because they compete with the substrate for the active site,"},{"Start":"09:06.530 ","End":"09:10.160","Text":"whereas non-competitive they bind a different site."},{"Start":"09:10.160 ","End":"09:11.750","Text":"Therefore, they\u0027re not competing for"},{"Start":"09:11.750 ","End":"09:15.725","Text":"the same active site rather they result in a change in"},{"Start":"09:15.725 ","End":"09:23.355","Text":"confirmation so that the active site is no longer optimal in binding its substrate."},{"Start":"09:23.355 ","End":"09:28.899","Text":"Inhibition it doesn\u0027t need to be either or."},{"Start":"09:28.899 ","End":"09:32.225","Text":"Rather in many systems there can be"},{"Start":"09:32.225 ","End":"09:34.700","Text":"both allosteric activators as well as"},{"Start":"09:34.700 ","End":"09:39.955","Text":"competitive inhibitors that help with the regulation in the system."},{"Start":"09:39.955 ","End":"09:43.775","Text":"With this we completed part 2 of enzymes."},{"Start":"09:43.775 ","End":"09:47.330","Text":"In this part of the overview you hopefully learn to describe"},{"Start":"09:47.330 ","End":"09:52.080","Text":"models of enzyme function and describe the role of enzymes in metabolic pathways."}],"ID":30125},{"Watched":false,"Name":"Enzymes Part 3","Duration":"6m 55s","ChapterTopicVideoID":28614,"CourseChapterTopicPlaylistID":286643,"HasSubtitles":true,"ThumbnailPath":null,"UploadDate":null,"DurationForVideoObject":null,"Description":null,"MetaTitle":null,"MetaDescription":null,"Canonical":null,"VideoComments":[],"Subtitles":[{"Start":"00:00.410 ","End":"00:05.805","Text":"Welcome to Part 3 of enzymes."},{"Start":"00:05.805 ","End":"00:07.440","Text":"By the end of this part,"},{"Start":"00:07.440 ","End":"00:12.030","Text":"you\u0027ll be able to discuss enzyme regulation by various factors."},{"Start":"00:12.030 ","End":"00:14.833","Text":"We\u0027re going to expand on the idea,"},{"Start":"00:14.833 ","End":"00:18.725","Text":"and the terms of allosteric which we introduced before,"},{"Start":"00:18.725 ","End":"00:24.335","Text":"and specifically allosteric activation and inhibition by enzymes."},{"Start":"00:24.335 ","End":"00:27.170","Text":"Now let\u0027s expand on the term allosteric,"},{"Start":"00:27.170 ","End":"00:30.080","Text":"which we introduced within non-competitive inhibition since"},{"Start":"00:30.080 ","End":"00:33.605","Text":"there was both allosteric activation, and inhibition."},{"Start":"00:33.605 ","End":"00:36.200","Text":"Most allosterically regulated enzymes are made from"},{"Start":"00:36.200 ","End":"00:39.080","Text":"polypeptides subunits each with its own active site."},{"Start":"00:39.080 ","End":"00:41.480","Text":"What we see here is a polypeptide subunits."},{"Start":"00:41.480 ","End":"00:44.075","Text":"In this example, we see 4 of these,"},{"Start":"00:44.075 ","End":"00:54.638","Text":"4 sites that form this allosterically regulated enzyme with 4 active sites."},{"Start":"00:54.638 ","End":"00:58.160","Text":"This allosteric enzyme has 4 Subunits, 1,"},{"Start":"00:58.160 ","End":"01:00.390","Text":"2, 3,"},{"Start":"01:00.390 ","End":"01:02.660","Text":"4, with 1 of 4 active sites."},{"Start":"01:02.660 ","End":"01:04.130","Text":"This is one of them."},{"Start":"01:04.130 ","End":"01:06.260","Text":"You have a regulatory site,"},{"Start":"01:06.260 ","End":"01:09.080","Text":"1 of 4, these are regulatory sites."},{"Start":"01:09.080 ","End":"01:13.805","Text":"Each subunit has its own active site."},{"Start":"01:13.805 ","End":"01:19.181","Text":"The enzyme complex can be in 1 of 2 states,"},{"Start":"01:19.181 ","End":"01:23.870","Text":"in active state or an inactive state as seen in the figure here,"},{"Start":"01:23.870 ","End":"01:26.000","Text":"you have the active form of"},{"Start":"01:26.000 ","End":"01:30.740","Text":"the enzyme complex or the inactive form of the enzyme complex."},{"Start":"01:30.740 ","End":"01:34.820","Text":"You have the active site in the active form and then in the inactive form,"},{"Start":"01:34.820 ","End":"01:38.330","Text":"something happened with the enzyme conformation so that it folded over,"},{"Start":"01:38.330 ","End":"01:44.420","Text":"and now it\u0027s blocking the pocket so that the substrate can\u0027t fit into the active site."},{"Start":"01:44.420 ","End":"01:46.115","Text":"This is the inactive form."},{"Start":"01:46.115 ","End":"01:50.360","Text":"These are the 2 forms that you find the enzyme complex in,"},{"Start":"01:50.360 ","End":"01:56.300","Text":"the binding of an allosteric activators stabilizes the active arrangement of the enzyme."},{"Start":"01:56.300 ","End":"01:59.990","Text":"You see here. This is the active form and"},{"Start":"01:59.990 ","End":"02:04.520","Text":"the allosteric activator stabilizes the active arrangement."},{"Start":"02:04.520 ","End":"02:09.103","Text":"This activator now bound here or it can bind here 1 of the 4 sites,"},{"Start":"02:09.103 ","End":"02:12.874","Text":"and it has stabilized the active form so that now"},{"Start":"02:12.874 ","End":"02:16.610","Text":"this enzyme complex is an active form and"},{"Start":"02:16.610 ","End":"02:20.525","Text":"can function and catalyze reactions continuously."},{"Start":"02:20.525 ","End":"02:25.520","Text":"But, you also have a change that can occur into an inactive form."},{"Start":"02:25.520 ","End":"02:31.934","Text":"These just occur, these oscillate between active and inactive form in the cell regularly"},{"Start":"02:31.934 ","End":"02:35.300","Text":"unless you have an allosteric inhibitor which"},{"Start":"02:35.300 ","End":"02:39.860","Text":"stabilizes the inactive arrangement of the enzymes."},{"Start":"02:39.860 ","End":"02:42.125","Text":"So here you have the allosteric inhibitor."},{"Start":"02:42.125 ","End":"02:47.690","Text":"It also will bind into one of the regulatory sites,1 of the 4."},{"Start":"02:47.690 ","End":"02:49.408","Text":"See it binds here,"},{"Start":"02:49.408 ","End":"02:53.750","Text":"and now it stabilize the inactive form so that now"},{"Start":"02:53.750 ","End":"03:00.460","Text":"the enzyme comics is in this form catalysis of the reactions will not occur."},{"Start":"03:00.460 ","End":"03:04.475","Text":"Once you either have the allosteric activator or the allosteric inhibitor,"},{"Start":"03:04.475 ","End":"03:06.170","Text":"you will no longer see"},{"Start":"03:06.170 ","End":"03:09.605","Text":"this free oscillation between the active form and an inactive form."},{"Start":"03:09.605 ","End":"03:15.635","Text":"This helps with the regulation of reactions within the cell."},{"Start":"03:15.635 ","End":"03:17.750","Text":"Now let\u0027s talk about another type of inhibition."},{"Start":"03:17.750 ","End":"03:21.440","Text":"You have the feedback inhibition and it\u0027s negative feedback."},{"Start":"03:21.440 ","End":"03:23.390","Text":"We see an example here."},{"Start":"03:23.390 ","End":"03:28.490","Text":"The idea here is that the end product of a metabolic pathway blocks to production."},{"Start":"03:28.490 ","End":"03:33.575","Text":"In the figure, we have an enzyme that turns this substrate,"},{"Start":"03:33.575 ","End":"03:38.825","Text":"we\u0027ll call this Substrate 1, this triangle."},{"Start":"03:38.825 ","End":"03:45.580","Text":"It turns it into Product 1."},{"Start":"03:45.580 ","End":"03:49.760","Text":"This enzymatic reaction of Enzyme 1 turns this triangle,"},{"Start":"03:49.760 ","End":"03:50.990","Text":"the Substrate 1 to Product,"},{"Start":"03:50.990 ","End":"03:56.465","Text":"1, Product 1 is this purple rod, this purple rectangle."},{"Start":"03:56.465 ","End":"04:03.215","Text":"Now, this is just an example of a specific system,"},{"Start":"04:03.215 ","End":"04:09.560","Text":"a specific or a certain metabolic pathway in a cell just to visualize,"},{"Start":"04:09.560 ","End":"04:14.795","Text":"and have the idea of negative inhibition integrated and understood."},{"Start":"04:14.795 ","End":"04:21.140","Text":"We have Substrate 2 here that is used by Enzyme 2."},{"Start":"04:21.140 ","End":"04:25.005","Text":"This Product 1 of Enzyme 1,"},{"Start":"04:25.005 ","End":"04:28.369","Text":"which is now Substrate 2 of Enzyme 2 in the system,"},{"Start":"04:28.369 ","End":"04:33.115","Text":"for this system is an intermediate substrate A,"},{"Start":"04:33.115 ","End":"04:37.490","Text":"because it\u0027s the intermediate substrate for the system."},{"Start":"04:37.490 ","End":"04:40.296","Text":"Now intermediate substrate A which can"},{"Start":"04:40.296 ","End":"04:43.145","Text":"call Substrate 2 is used by Enzyme 2 this purple rod."},{"Start":"04:43.145 ","End":"04:48.620","Text":"The purple rectangle is turned into this fuchsia pink blob,"},{"Start":"04:48.620 ","End":"04:52.280","Text":"which is actually Product 2 of Enzyme 2, in essence,"},{"Start":"04:52.280 ","End":"04:55.020","Text":"it\u0027s going to be Substrate 3 for"},{"Start":"04:55.020 ","End":"04:59.060","Text":"Enzyme 3 and for the system it\u0027s intermediate substrate B."},{"Start":"04:59.060 ","End":"05:01.040","Text":"So you have these 2 intermediate substrates."},{"Start":"05:01.040 ","End":"05:03.485","Text":"Now Enzyme 3 will take this blob,"},{"Start":"05:03.485 ","End":"05:06.860","Text":"and turn it into Product 3,"},{"Start":"05:06.860 ","End":"05:11.840","Text":"which is actually the end-product for the system."},{"Start":"05:11.840 ","End":"05:19.880","Text":"Now, this end product binds to an allosteric site in the initial enzyme,"},{"Start":"05:19.880 ","End":"05:24.950","Text":"in Enzyme 1 and now this Pac-Man is triangle has shifted to"},{"Start":"05:24.950 ","End":"05:28.520","Text":"a different shape so that this conformational change that"},{"Start":"05:28.520 ","End":"05:32.510","Text":"occurred by this allosteric inhibition,"},{"Start":"05:32.510 ","End":"05:35.735","Text":"non-competitive inhibition, this end-product binding,"},{"Start":"05:35.735 ","End":"05:43.700","Text":"resulting in the fact that this Enzyme 1 no longer binds with Substrate 1."},{"Start":"05:43.700 ","End":"05:46.820","Text":"So this Substrate 1 can\u0027t bind to the active site of the enzyme and"},{"Start":"05:46.820 ","End":"05:50.885","Text":"the metabolic pathway doesn\u0027t continue to occur."},{"Start":"05:50.885 ","End":"05:55.130","Text":"Now, this is important because this"},{"Start":"05:55.130 ","End":"05:57.020","Text":"prevents the cell from wasting"},{"Start":"05:57.020 ","End":"06:00.560","Text":"chemical resources by synthesizing more product than is needed."},{"Start":"06:00.560 ","End":"06:02.225","Text":"Once we have enough product,"},{"Start":"06:02.225 ","End":"06:04.730","Text":"we don\u0027t want the cell to continue utilizing energy and"},{"Start":"06:04.730 ","End":"06:07.850","Text":"substrate to create more product that is not needed anymore."},{"Start":"06:07.850 ","End":"06:12.950","Text":"Therefore, the end product of the pathway blocks it from continuing."},{"Start":"06:12.950 ","End":"06:15.515","Text":"But once the green squares have been used up,"},{"Start":"06:15.515 ","End":"06:20.735","Text":"either by other forums are broken down or integrated into these enzymes,"},{"Start":"06:20.735 ","End":"06:24.740","Text":"then the enzyme can go back to its functional confirmation"},{"Start":"06:24.740 ","End":"06:30.110","Text":"in active form and the cell will be able to synthesize the needed product again."},{"Start":"06:30.110 ","End":"06:34.445","Text":"As we completed the overview of enzymes, and by now,"},{"Start":"06:34.445 ","End":"06:38.540","Text":"you should be able to describe the role of enzymes in metabolic pathways,"},{"Start":"06:38.540 ","End":"06:41.299","Text":"explain how enzymes function as molecular catalysts,"},{"Start":"06:41.299 ","End":"06:44.405","Text":"and discuss enzyme regulation by various factors."},{"Start":"06:44.405 ","End":"06:48.748","Text":"After this section, you have a good overview of enzymes,"},{"Start":"06:48.748 ","End":"06:55.020","Text":"and we\u0027re going to dive back into specific in the next section."}],"ID":30126},{"Watched":false,"Name":"Exercise 3","Duration":"2m 6s","ChapterTopicVideoID":28615,"CourseChapterTopicPlaylistID":286643,"HasSubtitles":true,"ThumbnailPath":null,"UploadDate":null,"DurationForVideoObject":null,"Description":null,"MetaTitle":null,"MetaDescription":null,"Canonical":null,"VideoComments":[],"Subtitles":[{"Start":"00:00.000 ","End":"00:04.095","Text":"Welcome to an exercise covering the topic of enzymes."},{"Start":"00:04.095 ","End":"00:07.070","Text":"Which of the following is not true about enzymes?"},{"Start":"00:07.070 ","End":"00:09.380","Text":"A, they increase delta G of reaction."},{"Start":"00:09.380 ","End":"00:12.060","Text":"B, they\u0027re usually made of amino acids."},{"Start":"00:12.060 ","End":"00:15.375","Text":"C, they lower the activation energy of chemical reactions."},{"Start":"00:15.375 ","End":"00:18.180","Text":"D, each one is specific to the particular substrate,"},{"Start":"00:18.180 ","End":"00:20.550","Text":"or substrates to which it binds."},{"Start":"00:20.550 ","End":"00:26.819","Text":"Let\u0027s talk about the idea of what we said enzymes do right there, catalyst of reaction."},{"Start":"00:26.819 ","End":"00:29.985","Text":"A, they increase delta G of reactions."},{"Start":"00:29.985 ","End":"00:32.110","Text":"Well, if they increase delta G of reactions,"},{"Start":"00:32.110 ","End":"00:35.445","Text":"it wouldn\u0027t necessarily be beneficial for the reaction to occur."},{"Start":"00:35.445 ","End":"00:40.130","Text":"We actually talked about that it doesn\u0027t affect the delta G of the reaction."},{"Start":"00:40.130 ","End":"00:42.740","Text":"It seems like this would be false."},{"Start":"00:42.740 ","End":"00:44.630","Text":"Therefore, this could be"},{"Start":"00:44.630 ","End":"00:47.450","Text":"our answer because we\u0027re looking for what isn\u0027t true about enzymes."},{"Start":"00:47.450 ","End":"00:50.210","Text":"But, let\u0027s cover the next ones and see about them."},{"Start":"00:50.210 ","End":"00:52.985","Text":"B, they are usually made of amino acids."},{"Start":"00:52.985 ","End":"01:00.620","Text":"We did mention the enzymes are almost always proteins."},{"Start":"01:00.620 ","End":"01:06.470","Text":"That means since proteins are made of amino acids,"},{"Start":"01:06.470 ","End":"01:09.560","Text":"that we can say they\u0027re usually made of amino acids."},{"Start":"01:09.560 ","End":"01:11.780","Text":"This seems like it could be true,"},{"Start":"01:11.780 ","End":"01:16.345","Text":"but maybe there\u0027s something that\u0027s a little less true so let\u0027s move on."},{"Start":"01:16.345 ","End":"01:20.090","Text":"C, they lower the activation energy of chemical reactions."},{"Start":"01:20.090 ","End":"01:22.190","Text":"Well, that is what we said that they do,"},{"Start":"01:22.190 ","End":"01:24.140","Text":"they don\u0027t change the delta G,"},{"Start":"01:24.140 ","End":"01:28.430","Text":"but they do change and lower the activation energy of reaction."},{"Start":"01:28.430 ","End":"01:31.505","Text":"They make that hill smaller so that the reaction can occur more efficiently."},{"Start":"01:31.505 ","End":"01:33.405","Text":"This is a true statement."},{"Start":"01:33.405 ","End":"01:35.555","Text":"I would say that B is incorrect,"},{"Start":"01:35.555 ","End":"01:38.000","Text":"C is incorrect because they\u0027re both true."},{"Start":"01:38.000 ","End":"01:41.740","Text":"Let\u0027s see about D. Each one is specific to the particular substrate,"},{"Start":"01:41.740 ","End":"01:43.310","Text":"or substrates to which it binds."},{"Start":"01:43.310 ","End":"01:45.800","Text":"Well, we spoke about enzyme specificity."},{"Start":"01:45.800 ","End":"01:49.684","Text":"The active site is specific to an actual substrate."},{"Start":"01:49.684 ","End":"01:51.470","Text":"Therefore, this is a true statement."},{"Start":"01:51.470 ","End":"01:54.015","Text":"I would say it\u0027s not our answer."},{"Start":"01:54.015 ","End":"01:56.265","Text":"Therefore it leaves us with A,"},{"Start":"01:56.265 ","End":"01:58.785","Text":"this is the false statement."},{"Start":"01:58.785 ","End":"02:03.305","Text":"Enzymes do not increase delta G of reactions."},{"Start":"02:03.305 ","End":"02:06.900","Text":"With that, we completed this exercise."}],"ID":30127},{"Watched":false,"Name":"Exercise 4","Duration":"2m 45s","ChapterTopicVideoID":28616,"CourseChapterTopicPlaylistID":286643,"HasSubtitles":true,"ThumbnailPath":null,"UploadDate":null,"DurationForVideoObject":null,"Description":null,"MetaTitle":null,"MetaDescription":null,"Canonical":null,"VideoComments":[],"Subtitles":[{"Start":"00:00.330 ","End":"00:04.105","Text":"Let\u0027s dive into another exercise within Enzymes."},{"Start":"00:04.105 ","End":"00:09.320","Text":"An allosteric inhibitor does which of the following: a,"},{"Start":"00:09.320 ","End":"00:11.380","Text":"binds to an enzyme away from the active site"},{"Start":"00:11.380 ","End":"00:13.480","Text":"and changes the conformation of the active site,"},{"Start":"00:13.480 ","End":"00:17.155","Text":"increasing its affinity for substrate binding, b,"},{"Start":"00:17.155 ","End":"00:21.555","Text":"binds to the active site and blocks it from binding substrate, c,"},{"Start":"00:21.555 ","End":"00:23.020","Text":"binds to an enzyme away from"},{"Start":"00:23.020 ","End":"00:25.300","Text":"the active site and changes the conformation of the active site,"},{"Start":"00:25.300 ","End":"00:28.090","Text":"decreasing its affinity for the substrate, or d,"},{"Start":"00:28.090 ","End":"00:31.375","Text":"binds directly to the active site and mimics the substrate?"},{"Start":"00:31.375 ","End":"00:35.389","Text":"We talked about allosteric inhibitors."},{"Start":"00:35.389 ","End":"00:43.325","Text":"These are actual non competitive inhibitors,"},{"Start":"00:43.325 ","End":"00:48.215","Text":"and what did we say are non-competitive versus competitive?"},{"Start":"00:48.215 ","End":"00:51.935","Text":"A competitive inhibitor is one that competes"},{"Start":"00:51.935 ","End":"00:56.080","Text":"with the substrate in binding to the active site."},{"Start":"00:56.080 ","End":"00:58.820","Text":"The non-competitive therefore,"},{"Start":"00:58.820 ","End":"01:02.240","Text":"does not bind to the active site."},{"Start":"01:02.240 ","End":"01:05.645","Text":"If we look at our options here,"},{"Start":"01:05.645 ","End":"01:09.260","Text":"binds away from the active site,"},{"Start":"01:09.260 ","End":"01:12.605","Text":"binds to the active site,"},{"Start":"01:12.605 ","End":"01:16.975","Text":"binds away from the active site,"},{"Start":"01:16.975 ","End":"01:19.880","Text":"here we go directly to the active site."},{"Start":"01:19.880 ","End":"01:25.100","Text":"Allosteric inhibitor is a non competitive inhibitor, therefore,"},{"Start":"01:25.100 ","End":"01:27.770","Text":"we can eliminate the ones that bind to the active site,"},{"Start":"01:27.770 ","End":"01:30.240","Text":"but just us think about it."},{"Start":"01:30.240 ","End":"01:32.010","Text":"If we want to eliminate binds to the active site,"},{"Start":"01:32.010 ","End":"01:33.885","Text":"and blocks it from binding substrate,"},{"Start":"01:33.885 ","End":"01:37.205","Text":"this sounds like the competitive inhibitor,"},{"Start":"01:37.205 ","End":"01:38.720","Text":"so we can eliminate this."},{"Start":"01:38.720 ","End":"01:42.095","Text":"D, binds directly to the active site and mimics the substrate,"},{"Start":"01:42.095 ","End":"01:46.280","Text":"we didn\u0027t even talk about anything of this specifically,"},{"Start":"01:46.280 ","End":"01:48.050","Text":"so we eliminate this."},{"Start":"01:48.050 ","End":"01:51.680","Text":"Let\u0027s go to a, binds an enzyme away from the active site,"},{"Start":"01:51.680 ","End":"01:54.060","Text":"and changes the conformation of the active site,"},{"Start":"01:54.060 ","End":"01:58.430","Text":"this is true, increasing its affinity for substrate binding."},{"Start":"01:58.430 ","End":"02:00.335","Text":"See if it increased its affinity,"},{"Start":"02:00.335 ","End":"02:02.130","Text":"it means that it would bind better,"},{"Start":"02:02.130 ","End":"02:05.555","Text":"more efficiently, that wouldn\u0027t necessarily be an inhibitor, would it?"},{"Start":"02:05.555 ","End":"02:08.270","Text":"Let\u0027s go over to c, binds an enzyme away from"},{"Start":"02:08.270 ","End":"02:11.255","Text":"the active site and changes the conformation of the active site,"},{"Start":"02:11.255 ","End":"02:13.880","Text":"decreasing its affinity for the substrate."},{"Start":"02:13.880 ","End":"02:15.635","Text":"Well, by decreasing its affinity,"},{"Start":"02:15.635 ","End":"02:18.470","Text":"it actually reduces the catalysis of the reaction,"},{"Start":"02:18.470 ","End":"02:20.885","Text":"and therefore it inhibits it,"},{"Start":"02:20.885 ","End":"02:22.700","Text":"so it seems like c would be correct,"},{"Start":"02:22.700 ","End":"02:25.715","Text":"and a would be incorrect."},{"Start":"02:25.715 ","End":"02:28.055","Text":"We can eliminate a,"},{"Start":"02:28.055 ","End":"02:29.920","Text":"we can eliminate b,"},{"Start":"02:29.920 ","End":"02:31.580","Text":"we think c is correct,"},{"Start":"02:31.580 ","End":"02:32.820","Text":"we will eliminate d,"},{"Start":"02:32.820 ","End":"02:37.700","Text":"and it leaves us with an allosteric inhibitor binds an enzyme away from the active site,"},{"Start":"02:37.700 ","End":"02:39.530","Text":"and changes the conformation of the active site,"},{"Start":"02:39.530 ","End":"02:42.655","Text":"decreasing its affinity for the substrate."},{"Start":"02:42.655 ","End":"02:45.500","Text":"With that, we completed this exercise."}],"ID":30128},{"Watched":false,"Name":"Exercise 5","Duration":"2m 28s","ChapterTopicVideoID":28617,"CourseChapterTopicPlaylistID":286643,"HasSubtitles":true,"ThumbnailPath":null,"UploadDate":null,"DurationForVideoObject":null,"Description":null,"MetaTitle":null,"MetaDescription":null,"Canonical":null,"VideoComments":[],"Subtitles":[{"Start":"00:00.000 ","End":"00:04.770","Text":"We have a third exercise within enzymes. Let\u0027s dive in."},{"Start":"00:04.770 ","End":"00:07.170","Text":"Which of the following analogies best describes"},{"Start":"00:07.170 ","End":"00:09.945","Text":"the induced fit model of the enzyme-substrate binding."},{"Start":"00:09.945 ","End":"00:15.209","Text":"Remember we talked about 2 models for enzyme function."},{"Start":"00:15.209 ","End":"00:17.333","Text":"We talked about induced fit,"},{"Start":"00:17.333 ","End":"00:18.765","Text":"and do you remember the other one?"},{"Start":"00:18.765 ","End":"00:25.320","Text":"The other one was lock and key model."},{"Start":"00:25.320 ","End":"00:27.810","Text":"Which of the following analogies best described"},{"Start":"00:27.810 ","End":"00:30.255","Text":"the induced-fit model of enzyme-substrate binding?"},{"Start":"00:30.255 ","End":"00:32.415","Text":"A. A hug between 2 people."},{"Start":"00:32.415 ","End":"00:34.785","Text":"B. A key fitting into a lock."},{"Start":"00:34.785 ","End":"00:37.678","Text":"C. A square peg fitting through the square hole,"},{"Start":"00:37.678 ","End":"00:41.380","Text":"and a round peg fitting through the round hole of a children\u0027s toy."},{"Start":"00:41.380 ","End":"00:47.025","Text":"Or, D. The fitting together of 2 jigsaw puzzle pieces."},{"Start":"00:47.025 ","End":"00:49.850","Text":"When we talk about the induced fit,"},{"Start":"00:49.850 ","End":"00:53.540","Text":"it is one where result in a conformational change of"},{"Start":"00:53.540 ","End":"00:57.350","Text":"the active site of the enzyme as the substrate,"},{"Start":"00:57.350 ","End":"01:01.549","Text":"and the enzyme come closely together so that they become"},{"Start":"01:01.549 ","End":"01:06.395","Text":"more fitting in the transition state whereas initially,"},{"Start":"01:06.395 ","End":"01:08.270","Text":"they are not an exact fit."},{"Start":"01:08.270 ","End":"01:11.105","Text":"Going through that, a hug between 2 people."},{"Start":"01:11.105 ","End":"01:13.000","Text":"Let\u0027s think about that and pass on to B."},{"Start":"01:13.000 ","End":"01:14.660","Text":"A key fitting into a lock."},{"Start":"01:14.660 ","End":"01:19.235","Text":"We know a key fitting into a lock fits the lock and key model, so it\u0027s not this one."},{"Start":"01:19.235 ","End":"01:23.490","Text":"Square peg fitting through the square hole around peg fitting through the round hole."},{"Start":"01:23.490 ","End":"01:25.490","Text":"That\u0027s the idea of a lock and key."},{"Start":"01:25.490 ","End":"01:26.960","Text":"There\u0027s an exact fit."},{"Start":"01:26.960 ","End":"01:28.445","Text":"I would say this isn\u0027t it."},{"Start":"01:28.445 ","End":"01:31.370","Text":"Then we have the fitting together 2 jigsaw puzzle pieces."},{"Start":"01:31.370 ","End":"01:33.080","Text":"Well, if they fit exactly together,"},{"Start":"01:33.080 ","End":"01:34.880","Text":"that again is the lock and key."},{"Start":"01:34.880 ","End":"01:36.709","Text":"They fit together exactly,"},{"Start":"01:36.709 ","End":"01:41.535","Text":"that happens in the induced fit at the transition state,"},{"Start":"01:41.535 ","End":"01:45.345","Text":"but initially, it\u0027s not that way."},{"Start":"01:45.345 ","End":"01:46.830","Text":"A hug between 2 people,"},{"Start":"01:46.830 ","End":"01:50.974","Text":"2 people don\u0027t match exactly each other\u0027s shapes."},{"Start":"01:50.974 ","End":"01:57.860","Text":"Yet the 2 arms that come together and bind result in an interaction, and a bond."},{"Start":"01:57.860 ","End":"02:02.330","Text":"The other example that I gave you was a conforming mattress."},{"Start":"02:02.330 ","End":"02:03.755","Text":"Like a conforming pillow."},{"Start":"02:03.755 ","End":"02:07.055","Text":"The mattress initially has a flat surface,"},{"Start":"02:07.055 ","End":"02:09.770","Text":"but when you lie on top of it,"},{"Start":"02:09.770 ","End":"02:15.920","Text":"it actually conforms to your body to have an exact fit so we can eliminate b,"},{"Start":"02:15.920 ","End":"02:20.690","Text":"c, and d that fit the lock and key model."},{"Start":"02:20.690 ","End":"02:28.050","Text":"A, is an example that best describes the induced fit from the other examples."}],"ID":30129},{"Watched":false,"Name":"The Transition State","Duration":"4m 47s","ChapterTopicVideoID":28618,"CourseChapterTopicPlaylistID":286643,"HasSubtitles":true,"ThumbnailPath":null,"UploadDate":null,"DurationForVideoObject":null,"Description":null,"MetaTitle":null,"MetaDescription":null,"Canonical":null,"VideoComments":[],"Subtitles":[{"Start":"00:00.000 ","End":"00:03.390","Text":"So as we talked about enzymes and enzyme function,"},{"Start":"00:03.390 ","End":"00:05.595","Text":"we introduced the idea of the transition state."},{"Start":"00:05.595 ","End":"00:08.400","Text":"By the end of this section, you\u0027ll be able to talk about"},{"Start":"00:08.400 ","End":"00:11.250","Text":"the transition state of an enzyme reaction further,"},{"Start":"00:11.250 ","End":"00:16.980","Text":"depth and weak interactions and the transition state and how these relate to each other."},{"Start":"00:16.980 ","End":"00:23.235","Text":"Weak interactions between enzyme and substrate are optimized in the transition state."},{"Start":"00:23.235 ","End":"00:26.585","Text":"Studies by Emil Fischer led him to propose in 1894,"},{"Start":"00:26.585 ","End":"00:29.945","Text":"that enzymes were structurally complementary to their substrates."},{"Start":"00:29.945 ","End":"00:34.850","Text":"Later, this was found to be super significant"},{"Start":"00:34.850 ","End":"00:39.995","Text":"in the ability of enzymes to do their function as a catalyst."},{"Start":"00:39.995 ","End":"00:44.255","Text":"The modern notion of enzymatic catalysis is as such,"},{"Start":"00:44.255 ","End":"00:49.415","Text":"first proposed by Michael Polanyi in 1921 and Haldane in 1930."},{"Start":"00:49.415 ","End":"00:53.510","Text":"Then elaborated by Linus Pauling in 1946."},{"Start":"00:53.510 ","End":"00:55.805","Text":"In order to catalyze reactions,"},{"Start":"00:55.805 ","End":"01:00.350","Text":"an enzyme must be complimentary to the reaction transition state."},{"Start":"01:00.350 ","End":"01:01.760","Text":"We have the figure here,"},{"Start":"01:01.760 ","End":"01:03.850","Text":"we have the reactants,"},{"Start":"01:03.850 ","End":"01:05.820","Text":"we have the product."},{"Start":"01:05.820 ","End":"01:08.330","Text":"Remember we have this transition state."},{"Start":"01:08.330 ","End":"01:11.840","Text":"Now this means the optimal interactions between substrate"},{"Start":"01:11.840 ","End":"01:15.530","Text":"and enzyme occur only in the transition state."},{"Start":"01:15.530 ","End":"01:18.560","Text":"Some weak interactions are formed in the ES complex,"},{"Start":"01:18.560 ","End":"01:19.820","Text":"the enzyme substrate complex."},{"Start":"01:19.820 ","End":"01:23.990","Text":"But the full complement of these weak interactions between"},{"Start":"01:23.990 ","End":"01:28.565","Text":"substrate and enzyme is formed when the substrate reaches the transition state."},{"Start":"01:28.565 ","End":"01:30.920","Text":"Again, this right here."},{"Start":"01:30.920 ","End":"01:35.000","Text":"The free energy, the binding energy released by the formation of"},{"Start":"01:35.000 ","End":"01:40.100","Text":"these interactions offsets the energy required to reach the top of the energy hill."},{"Start":"01:40.100 ","End":"01:44.335","Text":"The summation of the unfavorable positive activation energy,"},{"Start":"01:44.335 ","End":"01:48.945","Text":"Delta G plus plus and the favorable negative binding energy,"},{"Start":"01:48.945 ","End":"01:54.185","Text":"Delta G_B results in a lower net activation energy."},{"Start":"01:54.185 ","End":"01:55.820","Text":"Even on the enzyme,"},{"Start":"01:55.820 ","End":"02:00.140","Text":"the transition state is not a stable species,"},{"Start":"02:00.140 ","End":"02:05.975","Text":"but a brief point in time that the substrate spends atop an energy hill."},{"Start":"02:05.975 ","End":"02:08.460","Text":"This is a fleeting moment and"},{"Start":"02:08.460 ","End":"02:15.080","Text":"the enzyme catalyzed reaction is much faster than the uncatalyzed process."},{"Start":"02:15.080 ","End":"02:22.039","Text":"However, because the activation energy hill or the energy barrier is much smaller."},{"Start":"02:22.039 ","End":"02:26.915","Text":"So when we look at the reaction hill without the enzyme involvement,"},{"Start":"02:26.915 ","End":"02:33.950","Text":"EA without enzyme, the activation energy and activation energy with enzyme is lower."},{"Start":"02:33.950 ","End":"02:37.865","Text":"See this hill is now lower,"},{"Start":"02:37.865 ","End":"02:40.310","Text":"its height has been reduced thanks to the enzyme."},{"Start":"02:40.310 ","End":"02:42.050","Text":"The important principles that weak"},{"Start":"02:42.050 ","End":"02:44.810","Text":"binding interactions between the enzyme and the substrate provide"},{"Start":"02:44.810 ","End":"02:49.520","Text":"a substantial driving force for enzymatic catalysis."},{"Start":"02:49.520 ","End":"02:53.300","Text":"The groups on the substrate that are involved in these weak interactions"},{"Start":"02:53.300 ","End":"02:56.885","Text":"can be at some distance from the bonds that are broken or changed,"},{"Start":"02:56.885 ","End":"02:59.870","Text":"meaning that they don\u0027t have to be in close proximity,"},{"Start":"02:59.870 ","End":"03:06.795","Text":"but they can still function as contributors to this weak interaction."},{"Start":"03:06.795 ","End":"03:10.010","Text":"The weak interactions formed only in"},{"Start":"03:10.010 ","End":"03:15.620","Text":"the transition state make the primary contribution to the catalysis."},{"Start":"03:15.620 ","End":"03:19.850","Text":"The requirement for multiple weak interactions drive catalysis is"},{"Start":"03:19.850 ","End":"03:24.439","Text":"one reason why enzymes and some co-enzymes are so large."},{"Start":"03:24.439 ","End":"03:28.565","Text":"Explaining this concept of the enzyme needing to be large,"},{"Start":"03:28.565 ","End":"03:34.865","Text":"an enzyme must provide functional groups for ionic hydrogen bond and other interactions."},{"Start":"03:34.865 ","End":"03:37.340","Text":"An enzyme also must position these groups so that"},{"Start":"03:37.340 ","End":"03:41.200","Text":"binding energy is optimized in the transition state."},{"Start":"03:41.200 ","End":"03:49.084","Text":"Adequate binding is accomplished most readily by positioning a substrate in the cavity,"},{"Start":"03:49.084 ","End":"03:53.825","Text":"in the active site where it is removed from water."},{"Start":"03:53.825 ","End":"03:55.745","Text":"If we look at this figure here,"},{"Start":"03:55.745 ","End":"04:02.329","Text":"you see that the substrate is basically inside a deep pocket in the enzyme,"},{"Start":"04:02.329 ","End":"04:05.720","Text":"meaning that it\u0027s almost entirely engulfed and therefore it"},{"Start":"04:05.720 ","End":"04:09.440","Text":"is removed from the water from the aqueous solution of the cell."},{"Start":"04:09.440 ","End":"04:13.070","Text":"The size of proteins reflect the needs for"},{"Start":"04:13.070 ","End":"04:16.625","Text":"superstructure to keep interacting groups properly positioned,"},{"Start":"04:16.625 ","End":"04:20.510","Text":"and to keep the cavity from collapsing."},{"Start":"04:20.510 ","End":"04:26.120","Text":"This great size is what allows and helps the enzyme have"},{"Start":"04:26.120 ","End":"04:29.360","Text":"all these properties to allow for"},{"Start":"04:29.360 ","End":"04:33.290","Text":"the transition state to occur and for the activation energy,"},{"Start":"04:33.290 ","End":"04:37.940","Text":"the energy barrier to be reduced and for the reaction to create a better, faster rate."},{"Start":"04:37.940 ","End":"04:41.555","Text":"With this, we completed touching upon the transition state."},{"Start":"04:41.555 ","End":"04:44.300","Text":"We learned about the transition state of an enzyme reaction"},{"Start":"04:44.300 ","End":"04:47.790","Text":"and weak interactions and the transition state."}],"ID":30130},{"Watched":false,"Name":"Exercise 6","Duration":"36s","ChapterTopicVideoID":28619,"CourseChapterTopicPlaylistID":286643,"HasSubtitles":true,"ThumbnailPath":null,"UploadDate":null,"DurationForVideoObject":null,"Description":null,"MetaTitle":null,"MetaDescription":null,"Canonical":null,"VideoComments":[],"Subtitles":[{"Start":"00:00.000 ","End":"00:04.248","Text":"Welcome to the exercises within the transition state lesson."},{"Start":"00:04.248 ","End":"00:06.675","Text":"The modern notion of enzymatic catalysis."},{"Start":"00:06.675 ","End":"00:09.660","Text":"To find the modern notion of enzymatic catalysis as first proposed by"},{"Start":"00:09.660 ","End":"00:12.900","Text":"Michael Polanyi 1921 and Halden 1930,"},{"Start":"00:12.900 ","End":"00:15.960","Text":"and later elaborated by Linus Pauling in 1946."},{"Start":"00:15.960 ","End":"00:18.180","Text":"The modern notion of enzymatic catalysis"},{"Start":"00:18.180 ","End":"00:20.280","Text":"in essence says that in order to catalyze reaction,"},{"Start":"00:20.280 ","End":"00:23.760","Text":"the enzyme must be complimentary to the reaction transition state."},{"Start":"00:23.760 ","End":"00:26.250","Text":"This means that optimal interactions between substrate,"},{"Start":"00:26.250 ","End":"00:28.740","Text":"and enzyme occur in the transition state,"},{"Start":"00:28.740 ","End":"00:35.530","Text":"and basically signifies the importance of the transition state in the enzymatic reaction."}],"ID":30131},{"Watched":false,"Name":"Exercise 7","Duration":"3m 8s","ChapterTopicVideoID":28620,"CourseChapterTopicPlaylistID":286643,"HasSubtitles":true,"ThumbnailPath":null,"UploadDate":null,"DurationForVideoObject":null,"Description":null,"MetaTitle":null,"MetaDescription":null,"Canonical":null,"VideoComments":[],"Subtitles":[{"Start":"00:00.000 ","End":"00:03.660","Text":"Going over our knowledge about the transition state."},{"Start":"00:03.660 ","End":"00:05.955","Text":"Which statement is false and why?"},{"Start":"00:05.955 ","End":"00:09.315","Text":"I\u0027ll read through all of them, let it sink in,"},{"Start":"00:09.315 ","End":"00:10.935","Text":"let your brain process it,"},{"Start":"00:10.935 ","End":"00:13.380","Text":"and then we\u0027ll go over the answers 1 by 1."},{"Start":"00:13.380 ","End":"00:15.780","Text":"A, weak interactions between substrate and"},{"Start":"00:15.780 ","End":"00:18.990","Text":"enzyme are formed when the substrate reaches the transition state."},{"Start":"00:18.990 ","End":"00:21.900","Text":"B, the summation of the unfavorable, positive,"},{"Start":"00:21.900 ","End":"00:25.395","Text":"activation energy and the favorable, negative,"},{"Start":"00:25.395 ","End":"00:29.655","Text":"binding energy, Delta G_B results in a higher net activation energy."},{"Start":"00:29.655 ","End":"00:35.085","Text":"C, the transition state is not a stable species rather a brief point in time."},{"Start":"00:35.085 ","End":"00:39.702","Text":"D, the enzyme-catalyzed reaction is much faster because the hill is much smaller."},{"Start":"00:39.702 ","End":"00:41.015","Text":"Let\u0027s go back to A."},{"Start":"00:41.015 ","End":"00:43.790","Text":"Weak interactions between substrate and"},{"Start":"00:43.790 ","End":"00:47.165","Text":"enzyme are formed when the substrate reaches the transition state."},{"Start":"00:47.165 ","End":"00:52.280","Text":"Well, this was mentioned as playing an important role in the transition state,"},{"Start":"00:52.280 ","End":"00:58.565","Text":"and that is one of the ways that actual substrate and enzyme interaction"},{"Start":"00:58.565 ","End":"01:01.265","Text":"favors the reduction of"},{"Start":"01:01.265 ","End":"01:06.050","Text":"the energy barrier and therefor the transition and reaction can occur."},{"Start":"01:06.050 ","End":"01:08.060","Text":"So this is a true statement,"},{"Start":"01:08.060 ","End":"01:10.465","Text":"therefore, it\u0027s not our false statement."},{"Start":"01:10.465 ","End":"01:13.010","Text":"B, the summation of the unfavorable,"},{"Start":"01:13.010 ","End":"01:14.360","Text":"positive, activation energy,"},{"Start":"01:14.360 ","End":"01:15.845","Text":"Delta G plus plus,"},{"Start":"01:15.845 ","End":"01:20.720","Text":"and the favorable, negative,"},{"Start":"01:20.720 ","End":"01:25.843","Text":"binding energy results in a higher net activation energy."},{"Start":"01:25.843 ","End":"01:28.580","Text":"If this is the case,"},{"Start":"01:28.580 ","End":"01:30.890","Text":"it means, higher net activation energy,"},{"Start":"01:30.890 ","End":"01:35.330","Text":"that the reaction will have a much greater need for energy investment to"},{"Start":"01:35.330 ","End":"01:40.670","Text":"occur and therefore that wouldn\u0027t allow for the reaction to occur."},{"Start":"01:40.670 ","End":"01:45.380","Text":"This sounds like it is possibly your answer because it sounds false but let\u0027s"},{"Start":"01:45.380 ","End":"01:50.720","Text":"check C. The transition state is not a stable species rather a brief point in time."},{"Start":"01:50.720 ","End":"01:56.405","Text":"We did talk about the transition state as being a really brief moment in time."},{"Start":"01:56.405 ","End":"01:58.880","Text":"It is not a stable species,"},{"Start":"01:58.880 ","End":"02:02.308","Text":"rather a transition that is super brief."},{"Start":"02:02.308 ","End":"02:07.835","Text":"So this sounds like a true statement and therefore is not our answer."},{"Start":"02:07.835 ","End":"02:11.540","Text":"Let\u0027s go over D. The enzyme-catalyzed reaction"},{"Start":"02:11.540 ","End":"02:14.375","Text":"is much faster because the hill is much smaller."},{"Start":"02:14.375 ","End":"02:19.550","Text":"This hill, this represents our energy investment,"},{"Start":"02:19.550 ","End":"02:26.234","Text":"the energy barrier, the activation energy that is needed for the reaction to occur."},{"Start":"02:26.234 ","End":"02:28.550","Text":"When you add the enzyme,"},{"Start":"02:28.550 ","End":"02:32.030","Text":"it catalyzes the reaction in such a way that this is"},{"Start":"02:32.030 ","End":"02:35.795","Text":"smaller and therefore the reaction rate increases."},{"Start":"02:35.795 ","End":"02:37.970","Text":"So this is a true statement, it\u0027s not our answer."},{"Start":"02:37.970 ","End":"02:41.060","Text":"That leaves us with B, therefore,"},{"Start":"02:41.060 ","End":"02:44.496","Text":"B being the false statement;"},{"Start":"02:44.496 ","End":"02:46.550","Text":"the summation of the unfavorable, positive,"},{"Start":"02:46.550 ","End":"02:49.580","Text":"activation energy Delta G plus plus, and the favorable,"},{"Start":"02:49.580 ","End":"02:53.255","Text":"negative, binding energy Delta G_B results in a higher net activation energy."},{"Start":"02:53.255 ","End":"02:55.100","Text":"Why is this false?"},{"Start":"02:55.100 ","End":"02:57.245","Text":"Because it actually results in"},{"Start":"02:57.245 ","End":"03:03.890","Text":"a lower net activation energy and that\u0027s what allows for the reaction to take place."},{"Start":"03:03.890 ","End":"03:08.220","Text":"That is why an enzyme is considered a catalyst."}],"ID":30132},{"Watched":false,"Name":"Exercise 8","Duration":"4m 10s","ChapterTopicVideoID":28621,"CourseChapterTopicPlaylistID":286643,"HasSubtitles":true,"ThumbnailPath":null,"UploadDate":null,"DurationForVideoObject":null,"Description":null,"MetaTitle":null,"MetaDescription":null,"Canonical":null,"VideoComments":[],"Subtitles":[{"Start":"00:00.000 ","End":"00:05.640","Text":"What else do we learn about the transition state of the enzyme reaction?"},{"Start":"00:05.640 ","End":"00:07.785","Text":"Part I, which statement is true?"},{"Start":"00:07.785 ","End":"00:10.350","Text":"A, the free energy, binding energy,"},{"Start":"00:10.350 ","End":"00:12.630","Text":"released by the formation of weak interactions offsets"},{"Start":"00:12.630 ","End":"00:15.675","Text":"the energy required to reach the top of the energy hill."},{"Start":"00:15.675 ","End":"00:19.410","Text":"B, the enzyme-catalyzed reaction is much faster than"},{"Start":"00:19.410 ","End":"00:25.005","Text":"the uncatalyzed process because the energy barrier hill is canceled by enzyme presence."},{"Start":"00:25.005 ","End":"00:29.000","Text":"C, the groups on a substrate that are involved in the weak interactions"},{"Start":"00:29.000 ","End":"00:33.005","Text":"with the enzyme needs to be in close proximity to the bonds that are broken or changed."},{"Start":"00:33.005 ","End":"00:36.020","Text":"D, the requirement for multiple weak interactions to drive"},{"Start":"00:36.020 ","End":"00:39.975","Text":"catalysis is the reason for the big size of enzymes, and some coenzymes."},{"Start":"00:39.975 ","End":"00:41.795","Text":"E, all of the above."},{"Start":"00:41.795 ","End":"00:44.635","Text":"Let\u0027s do this one at a time."},{"Start":"00:44.635 ","End":"00:47.690","Text":"A, the free energy, the binding energy,"},{"Start":"00:47.690 ","End":"00:51.470","Text":"released by the formation of weak interactions offsets"},{"Start":"00:51.470 ","End":"00:55.700","Text":"the energy required to reach the top of the energy hill."},{"Start":"00:55.700 ","End":"00:59.030","Text":"What we did mention that these weak interactions that occur between"},{"Start":"00:59.030 ","End":"01:02.720","Text":"the enzyme and the substrate in the transition state are what"},{"Start":"01:02.720 ","End":"01:10.460","Text":"contribute by forming and reducing the actual activation energy and therefore,"},{"Start":"01:10.460 ","End":"01:13.550","Text":"the energy hill is smaller and"},{"Start":"01:13.550 ","End":"01:17.495","Text":"therefore can more easily reach the top of the energy hill."},{"Start":"01:17.495 ","End":"01:19.085","Text":"This sounds like a true statement."},{"Start":"01:19.085 ","End":"01:20.605","Text":"Let\u0027s move to b."},{"Start":"01:20.605 ","End":"01:23.390","Text":"The enzyme-catalyzed reaction is much faster than"},{"Start":"01:23.390 ","End":"01:29.240","Text":"the uncatalyzed process because the energy barrier hill is canceled by enzyme presence."},{"Start":"01:29.240 ","End":"01:32.525","Text":"What we saw with the figures that this is reduced,"},{"Start":"01:32.525 ","End":"01:36.545","Text":"not canceled, there was still an energy barrier. It\u0027s just smaller."},{"Start":"01:36.545 ","End":"01:39.485","Text":"This sounds it\u0027s a false statement."},{"Start":"01:39.485 ","End":"01:43.040","Text":"Let\u0027s go to c. The groups on the substrate they\u0027re involved in"},{"Start":"01:43.040 ","End":"01:45.545","Text":"the weak interactions with the enzyme"},{"Start":"01:45.545 ","End":"01:48.890","Text":"needs to be in close proximity to the bonds that are broken or changed."},{"Start":"01:48.890 ","End":"01:50.210","Text":"What we actually talked about,"},{"Start":"01:50.210 ","End":"01:53.620","Text":"the fact that that they don\u0027t need to be in close proximity,"},{"Start":"01:53.620 ","End":"01:57.080","Text":"they can be farther apart but still have these interactions,"},{"Start":"01:57.080 ","End":"01:59.990","Text":"so this sounds like a false statement."},{"Start":"01:59.990 ","End":"02:04.280","Text":"Let\u0027s go to d. The requirement for multiple weak interactions to drive"},{"Start":"02:04.280 ","End":"02:08.675","Text":"catalysis is the reason for the big size of enzymes and some coenzymes."},{"Start":"02:08.675 ","End":"02:11.585","Text":"This is something that we did mention,"},{"Start":"02:11.585 ","End":"02:16.475","Text":"but is it the reason for the big size or a contributing factor?"},{"Start":"02:16.475 ","End":"02:19.025","Text":"This one seems partially true."},{"Start":"02:19.025 ","End":"02:21.410","Text":"But let\u0027s look at e, all of the above."},{"Start":"02:21.410 ","End":"02:22.730","Text":"We know that these aren\u0027t true,"},{"Start":"02:22.730 ","End":"02:29.480","Text":"so it can\u0027t be e and that leaves us with a or d. This seems it\u0027s partially true,"},{"Start":"02:29.480 ","End":"02:32.480","Text":"but a seems it is completely true."},{"Start":"02:32.480 ","End":"02:34.460","Text":"Let\u0027s read it again. The free energy, binding energy,"},{"Start":"02:34.460 ","End":"02:37.310","Text":"released by the formation of weak attractions offsets"},{"Start":"02:37.310 ","End":"02:40.615","Text":"the energy required to reach the top of energy hill. This sounds true."},{"Start":"02:40.615 ","End":"02:42.920","Text":"The requirement for multiple weak interactions to drive"},{"Start":"02:42.920 ","End":"02:45.995","Text":"catalysis is the reason for the big size of enzymes and some coenzymes."},{"Start":"02:45.995 ","End":"02:47.660","Text":"This sounds true as well,"},{"Start":"02:47.660 ","End":"02:50.010","Text":"but it is only partially a reason,"},{"Start":"02:50.010 ","End":"02:51.735","Text":"so I would say,"},{"Start":"02:51.735 ","End":"02:53.625","Text":"let\u0027s go with a."},{"Start":"02:53.625 ","End":"02:57.450","Text":"The answer to b will be we\u0027ve eliminated b,"},{"Start":"02:57.450 ","End":"02:58.590","Text":"we\u0027ve eliminated c,"},{"Start":"02:58.590 ","End":"03:00.060","Text":"we\u0027ve eliminated d, therefore,"},{"Start":"03:00.060 ","End":"03:04.515","Text":"we\u0027ve eliminated e, and A is our correct answer."},{"Start":"03:04.515 ","End":"03:07.925","Text":"Part II. Correct the statements that are not true."},{"Start":"03:07.925 ","End":"03:09.710","Text":"Well, we said that a is true,"},{"Start":"03:09.710 ","End":"03:12.380","Text":"so we will leave it as is. Let\u0027s go to b."},{"Start":"03:12.380 ","End":"03:16.520","Text":"The enzyme-catalyzed reaction is much faster than the uncatalyzed process, thus far,"},{"Start":"03:16.520 ","End":"03:21.305","Text":"this is true because the energy barrier hill is canceled by the enzyme presence."},{"Start":"03:21.305 ","End":"03:23.144","Text":"Well, it is not canceled,"},{"Start":"03:23.144 ","End":"03:25.235","Text":"rather it is much smaller."},{"Start":"03:25.235 ","End":"03:29.030","Text":"It is reduced by the enzyme and therefore it is"},{"Start":"03:29.030 ","End":"03:32.980","Text":"smaller and it can then have a faster rate."},{"Start":"03:32.980 ","End":"03:36.470","Text":"C, the groups on the substrate that are involved in the weak interactions"},{"Start":"03:36.470 ","End":"03:40.100","Text":"with the enzyme needs to be in close proximity to the bonds that are broken or changed."},{"Start":"03:40.100 ","End":"03:42.530","Text":"They actually don\u0027t need to be in close proximity."},{"Start":"03:42.530 ","End":"03:43.915","Text":"We can say,"},{"Start":"03:43.915 ","End":"03:47.390","Text":"the groups on a substrate that are involved in the weak interactions can be at"},{"Start":"03:47.390 ","End":"03:50.900","Text":"some distance from the bonds that are broken or changed."},{"Start":"03:50.900 ","End":"03:53.810","Text":"D, the requirement for multiple weak interactions to drive"},{"Start":"03:53.810 ","End":"03:57.470","Text":"catalysis is the reason for the big size of enzymes and some coenzymes."},{"Start":"03:57.470 ","End":"03:59.165","Text":"We said there are other factors,"},{"Start":"03:59.165 ","End":"04:00.350","Text":"therefore, we can say,"},{"Start":"04:00.350 ","End":"04:03.590","Text":"the requirement for multiple weak interactions to drive catalysis is"},{"Start":"04:03.590 ","End":"04:07.700","Text":"the only one reason for the big size of enzymes and some coenzymes,"},{"Start":"04:07.700 ","End":"04:11.010","Text":"there are additional reasons."}],"ID":30133},{"Watched":false,"Name":"Exercise 9","Duration":"2m 30s","ChapterTopicVideoID":28622,"CourseChapterTopicPlaylistID":286643,"HasSubtitles":true,"ThumbnailPath":null,"UploadDate":null,"DurationForVideoObject":null,"Description":null,"MetaTitle":null,"MetaDescription":null,"Canonical":null,"VideoComments":[],"Subtitles":[{"Start":"00:00.020 ","End":"00:04.800","Text":"Whereas another exercise within the transition state of enzyme reaction."},{"Start":"00:04.800 ","End":"00:06.840","Text":"The requirement from multiple weak interactions to"},{"Start":"00:06.840 ","End":"00:08.760","Text":"drive catalysis is 1 reason why enzymes are"},{"Start":"00:08.760 ","End":"00:13.350","Text":"so large and they must provide these things for the interactions to successfully occur."},{"Start":"00:13.350 ","End":"00:15.570","Text":"An enzyme must provide."},{"Start":"00:15.570 ","End":"00:19.965","Text":"First thing, blank for ionic hydrogen bonds and other interactions."},{"Start":"00:19.965 ","End":"00:25.935","Text":"Next thing, position these groups so that blank is optimized in the blank state."},{"Start":"00:25.935 ","End":"00:31.755","Text":"Third, adequate binding is accomplished most readily by positioning a blank and a cavity,"},{"Start":"00:31.755 ","End":"00:37.695","Text":"the blank site where it is effectively removed from water."},{"Start":"00:37.695 ","End":"00:43.530","Text":"An enzyme must provide what for ionic hydrogen bond and other interaction?"},{"Start":"00:43.530 ","End":"00:45.290","Text":"The enzyme must have"},{"Start":"00:45.290 ","End":"00:52.475","Text":"some functional groups to allow for ionic hydrogen bonds and other interactions to occur."},{"Start":"00:52.475 ","End":"00:56.645","Text":"The enzyme also must provide a position for these groups"},{"Start":"00:56.645 ","End":"01:01.545","Text":"so that something is optimized in the something state."},{"Start":"01:01.545 ","End":"01:02.900","Text":"In this entire section,"},{"Start":"01:02.900 ","End":"01:05.330","Text":"we\u0027re talking about the transition state,"},{"Start":"01:05.330 ","End":"01:07.775","Text":"so what needs to be optimized?"},{"Start":"01:07.775 ","End":"01:14.265","Text":"What does the position of these interaction need to play a role in to allow for what?"},{"Start":"01:14.265 ","End":"01:15.635","Text":"For binding."},{"Start":"01:15.635 ","End":"01:19.220","Text":"Therefore, the enzyme must position these groups so"},{"Start":"01:19.220 ","End":"01:22.850","Text":"that binding energy is optimized in the transition state"},{"Start":"01:22.850 ","End":"01:30.455","Text":"so that it can reduce the total energy barrier and therefore allow the reaction to occur."},{"Start":"01:30.455 ","End":"01:35.390","Text":"Adequate binding is accomplished most readily by positioning what?"},{"Start":"01:35.390 ","End":"01:38.390","Text":"In a cavity and what is this cavity?"},{"Start":"01:38.390 ","End":"01:42.320","Text":"What is the site where it is effectively removed from water?"},{"Start":"01:42.320 ","End":"01:45.335","Text":"We talked about there is an area in the enzyme like"},{"Start":"01:45.335 ","End":"01:50.075","Text":"a pocket that allows for the substrate to interact."},{"Start":"01:50.075 ","End":"01:53.180","Text":"Adequate binding is accomplished most readily by positioning"},{"Start":"01:53.180 ","End":"01:55.730","Text":"a substrate in the enzyme cavity,"},{"Start":"01:55.730 ","End":"01:59.525","Text":"which is the active site of the enzyme,"},{"Start":"01:59.525 ","End":"02:01.820","Text":"where it is effectively removed from water,"},{"Start":"02:01.820 ","End":"02:03.380","Text":"from this aqueous solution,"},{"Start":"02:03.380 ","End":"02:05.180","Text":"aqueous environment in the cell,"},{"Start":"02:05.180 ","End":"02:08.780","Text":"which reduces its interaction with hydrogen bonding and"},{"Start":"02:08.780 ","End":"02:13.160","Text":"the aqueous solution or whatever other bonding and ionic bonding there may be."},{"Start":"02:13.160 ","End":"02:16.520","Text":"Reducing that and then allowing binding between"},{"Start":"02:16.520 ","End":"02:20.255","Text":"the enzyme and the substrate in this active site."},{"Start":"02:20.255 ","End":"02:24.350","Text":"The size of proteins reflects the need for super structures to keep"},{"Start":"02:24.350 ","End":"02:29.640","Text":"interacting groups properly positioned and to keep the cavity from collapsing."}],"ID":30134},{"Watched":false,"Name":"Binding Energy Part 1","Duration":"9m 23s","ChapterTopicVideoID":28606,"CourseChapterTopicPlaylistID":286643,"HasSubtitles":true,"ThumbnailPath":null,"UploadDate":null,"DurationForVideoObject":null,"Description":null,"MetaTitle":null,"MetaDescription":null,"Canonical":null,"VideoComments":[],"Subtitles":[{"Start":"00:00.000 ","End":"00:03.480","Text":"Welcome back to enzyme function."},{"Start":"00:03.480 ","End":"00:06.975","Text":"In this section, we will specifically talk about binding energy."},{"Start":"00:06.975 ","End":"00:10.860","Text":"We introduced the idea of binding energy and its significance"},{"Start":"00:10.860 ","End":"00:15.045","Text":"within enzyme function and enzyme substrate interaction and binding,"},{"Start":"00:15.045 ","End":"00:17.850","Text":"and we will talk about this further."},{"Start":"00:17.850 ","End":"00:19.050","Text":"By the end of this section,"},{"Start":"00:19.050 ","End":"00:23.325","Text":"you\u0027ll be able to describe the significance of binding energy,"},{"Start":"00:23.325 ","End":"00:26.985","Text":"what is needed for an enzymatic reaction to occur,"},{"Start":"00:26.985 ","End":"00:30.675","Text":"and talk about induced fit."},{"Start":"00:30.675 ","End":"00:33.555","Text":"Let\u0027s start with Part I,"},{"Start":"00:33.555 ","End":"00:36.690","Text":"this section is put to 3 parts,"},{"Start":"00:36.690 ","End":"00:41.385","Text":"each one by size for you to have it sink in and understand."},{"Start":"00:41.385 ","End":"00:43.805","Text":"Within Part I of binding energy,"},{"Start":"00:43.805 ","End":"00:46.910","Text":"you will learn about the significance of binding energy"},{"Start":"00:46.910 ","End":"00:50.705","Text":"and what is needed for an enzymatic reaction to occur."},{"Start":"00:50.705 ","End":"00:55.685","Text":"Binding energy contributes to reaction specificity and catalysis."},{"Start":"00:55.685 ","End":"00:59.120","Text":"Can we demonstrate quantitatively that binding energy accounts for"},{"Start":"00:59.120 ","End":"01:02.765","Text":"the huge rate accelerations brought about by enzymes?"},{"Start":"01:02.765 ","End":"01:05.690","Text":"Yes. As a point of reference,"},{"Start":"01:05.690 ","End":"01:08.045","Text":"we had introduced an equation that allowed us to"},{"Start":"01:08.045 ","End":"01:12.170","Text":"calculate the Delta G plus plus must be lowered by"},{"Start":"01:12.170 ","End":"01:15.410","Text":"about 5.7 kilojoules per mole to accelerate the first-order reaction"},{"Start":"01:15.410 ","End":"01:18.725","Text":"by a factor of 10 under conditions commonly found in cells."},{"Start":"01:18.725 ","End":"01:21.370","Text":"This is from the previous section."},{"Start":"01:21.370 ","End":"01:24.800","Text":"We know this can be measured."},{"Start":"01:24.800 ","End":"01:28.430","Text":"Now, let\u0027s explain the ideas behind this."},{"Start":"01:28.430 ","End":"01:32.300","Text":"The energy available from formation of a single weak interaction"},{"Start":"01:32.300 ","End":"01:36.605","Text":"is generally estimated to be 4-30 kilojoules per mole."},{"Start":"01:36.605 ","End":"01:40.190","Text":"The overall energy available from a number of"},{"Start":"01:40.190 ","End":"01:45.710","Text":"such interactions is therefore sufficient to lower activation energies by"},{"Start":"01:45.710 ","End":"01:49.880","Text":"the 60-100 kilo joules per mole required to explain"},{"Start":"01:49.880 ","End":"01:55.710","Text":"the large rate enhancements observed for many enzymes."},{"Start":"01:55.780 ","End":"02:01.580","Text":"You see here, the enzyme substrate interaction is"},{"Start":"02:01.580 ","End":"02:06.920","Text":"stabilized by hydrogen bonding or ionic and hydrophobic interactions."},{"Start":"02:06.920 ","End":"02:10.130","Text":"The energy available from these different weak interactions"},{"Start":"02:10.130 ","End":"02:14.315","Text":"as illustrated here is 40-30 kilojoules per mole,"},{"Start":"02:14.315 ","End":"02:17.239","Text":"but that is for a single interaction."},{"Start":"02:17.239 ","End":"02:18.500","Text":"But even in this illustration,"},{"Start":"02:18.500 ","End":"02:20.095","Text":"you\u0027re already seeing 4 of them,"},{"Start":"02:20.095 ","End":"02:23.225","Text":"so even if you\u0027re talking about that it\u0027s 3, it\u0027s 120."},{"Start":"02:23.225 ","End":"02:29.510","Text":"The overall energy available is sufficient to lower activation energies because there"},{"Start":"02:29.510 ","End":"02:35.825","Text":"are several of these interactions that occur between the substrate,"},{"Start":"02:35.825 ","End":"02:40.795","Text":"and this is the substrate right here, and the enzyme."},{"Start":"02:40.795 ","End":"02:44.450","Text":"These interactions where you have"},{"Start":"02:44.450 ","End":"02:50.900","Text":"these various weak bond formations that are occurring help explain"},{"Start":"02:50.900 ","End":"02:55.895","Text":"this energy reduction allowing the enhancement"},{"Start":"02:55.895 ","End":"03:01.160","Text":"of the rate of the reaction observed with the presence of enzymes."},{"Start":"03:01.160 ","End":"03:04.760","Text":"The same binding energy that provides energy for"},{"Start":"03:04.760 ","End":"03:08.960","Text":"catalysis also gives an enzyme its specificity,"},{"Start":"03:08.960 ","End":"03:14.375","Text":"the ability to discriminate between a substrate and a competing molecule."},{"Start":"03:14.375 ","End":"03:17.300","Text":"It\u0027s these specific interactions,"},{"Start":"03:17.300 ","End":"03:21.470","Text":"these binding energies that will occur between specific sequences,"},{"Start":"03:21.470 ","End":"03:26.585","Text":"specific proteins of enzymes and substrate is also"},{"Start":"03:26.585 ","End":"03:32.450","Text":"what helps with this specificity between the enzyme and the substrate."},{"Start":"03:32.450 ","End":"03:37.790","Text":"If an enzyme active site has functional groups arranged optimally to"},{"Start":"03:37.790 ","End":"03:43.880","Text":"form a variety of weak interactions with a particular substrate in the transition state,"},{"Start":"03:43.880 ","End":"03:49.340","Text":"the enzyme will not be able to interact to the same degree with any other molecule."},{"Start":"03:49.340 ","End":"03:53.150","Text":"If you see here the enzyme and the active site,"},{"Start":"03:53.150 ","End":"03:56.975","Text":"this pocket, the interaction that occurs between this substrate,"},{"Start":"03:56.975 ","End":"04:04.760","Text":"this particular sequence of residues in proteins or amino acids in"},{"Start":"04:04.760 ","End":"04:12.830","Text":"the active site with the residues of the enzyme is specific to the particular substrate."},{"Start":"04:12.830 ","End":"04:17.210","Text":"For example, if the substrate has a hydroxyl group that forms"},{"Start":"04:17.210 ","End":"04:22.135","Text":"a hydrogen bond with a specific glycine residue on the enzyme,"},{"Start":"04:22.135 ","End":"04:24.395","Text":"any molecule lacking a hydroxyl group,"},{"Start":"04:24.395 ","End":"04:29.510","Text":"that particular position will be a poorer substrate for the enzyme."},{"Start":"04:29.510 ","End":"04:35.270","Text":"This means while you have the substrate with a hydroxyl group,"},{"Start":"04:35.270 ","End":"04:40.235","Text":"it will be bound specifically and closely with the enzyme and"},{"Start":"04:40.235 ","End":"04:47.215","Text":"other substrates will not be able to compete with this designated substrate."},{"Start":"04:47.215 ","End":"04:51.770","Text":"In addition, any molecule with an extra functional group for which the enzyme has"},{"Start":"04:51.770 ","End":"04:57.005","Text":"no pocket or binding site is likely to be excluded from the enzyme."},{"Start":"04:57.005 ","End":"05:02.300","Text":"Meaning, if this functional group doesn\u0027t fit the active site,"},{"Start":"05:02.300 ","End":"05:05.855","Text":"the pocket, the binding site of the enzyme,"},{"Start":"05:05.855 ","End":"05:08.780","Text":"then there won\u0027t be an interaction."},{"Start":"05:08.780 ","End":"05:13.310","Text":"Rather there will be an expectation for these to fit for"},{"Start":"05:13.310 ","End":"05:18.725","Text":"the pocket to be optimally fitting for the substance."},{"Start":"05:18.725 ","End":"05:22.100","Text":"In general, specificity is derived from the formation of"},{"Start":"05:22.100 ","End":"05:27.005","Text":"many weak interactions between the enzyme and its specific substrate molecule."},{"Start":"05:27.005 ","End":"05:31.010","Text":"More than 80% of the enzymatic rate acceleration has been traced to"},{"Start":"05:31.010 ","End":"05:35.975","Text":"enzyme substrate interactions involving the phosphate group on carbon 3 of the substrate."},{"Start":"05:35.975 ","End":"05:41.360","Text":"A given enzyme might incorporate several types of mechanisms which are not mutually"},{"Start":"05:41.360 ","End":"05:46.805","Text":"exclusive that yield the reaction rate acceleration and its overall mechanism of action."},{"Start":"05:46.805 ","End":"05:51.470","Text":"For most enzymes, it is difficult to quantify the contribution of"},{"Start":"05:51.470 ","End":"05:54.620","Text":"any one catalytic mechanism to the rate and or"},{"Start":"05:54.620 ","End":"05:58.625","Text":"specificity of a particular enzyme catalyzed reaction."},{"Start":"05:58.625 ","End":"06:02.240","Text":"But we can say the binding energy makes"},{"Start":"06:02.240 ","End":"06:07.940","Text":"an important and sometimes the dominant contribution to catalysis."},{"Start":"06:07.940 ","End":"06:13.010","Text":"Consider what needs to occur for a reaction to take place."},{"Start":"06:13.010 ","End":"06:17.285","Text":"Prominent physical and thermodynamic factors contributing to Delta G plus plus,"},{"Start":"06:17.285 ","End":"06:20.480","Text":"the barrier of reaction might include,"},{"Start":"06:20.480 ","End":"06:23.230","Text":"and just to remind you, this is the Delta G plus plus,"},{"Start":"06:23.230 ","End":"06:28.039","Text":"or here the Delta G plus plus of the uncatalyzed reaction,"},{"Start":"06:28.039 ","End":"06:31.250","Text":"the one without an enzyme which is larger because"},{"Start":"06:31.250 ","End":"06:38.790","Text":"the catalyzer always reduces this Delta G plus plus 1."},{"Start":"06:38.790 ","End":"06:42.320","Text":"Prominent physical and thermodynamic factors contributing to"},{"Start":"06:42.320 ","End":"06:48.035","Text":"the Delta G plus plus might include a reduction in entropy,"},{"Start":"06:48.035 ","End":"06:53.110","Text":"in the form of decreased freedom of motion of 2 molecules in solution."},{"Start":"06:53.110 ","End":"06:57.530","Text":"Reduction in entropy, it\u0027s the reduction in free energy and"},{"Start":"06:57.530 ","End":"07:02.660","Text":"freedom of molecules to move around of their motion."},{"Start":"07:02.660 ","End":"07:08.690","Text":"Reduction in entropy means a reduction in freedom of motion of 2 molecules in solution."},{"Start":"07:08.690 ","End":"07:12.815","Text":"Two, the solvation shell of hydrogen bonded water"},{"Start":"07:12.815 ","End":"07:17.105","Text":"that surrounds and helps to stabilize most biomolecules in aqueous solution."},{"Start":"07:17.105 ","End":"07:21.679","Text":"Remember, we talked about this term, the solvation shell."},{"Start":"07:21.679 ","End":"07:27.545","Text":"This is what happens when water molecules"},{"Start":"07:27.545 ","End":"07:33.110","Text":"surround a certain molecule and create this shell."},{"Start":"07:33.110 ","End":"07:36.835","Text":"It\u0027s a hydration shell because it\u0027s water molecules that surround it."},{"Start":"07:36.835 ","End":"07:41.930","Text":"Three, the distortion of substrates that must occur in many reactions,"},{"Start":"07:41.930 ","End":"07:47.550","Text":"primarily electron redistribution that the substrate must undergo to react,"},{"Start":"07:47.550 ","End":"07:53.330","Text":"and 4, the need for proper alignment of catalytic functional groups on the enzyme."},{"Start":"07:53.330 ","End":"08:00.515","Text":"All these come together and binding energy can be used to overcome all these barriers."},{"Start":"08:00.515 ","End":"08:04.850","Text":"Again, what needs to occur for a reaction to take place is"},{"Start":"08:04.850 ","End":"08:08.603","Text":"prominent physical and thermodynamic factors contributing to Delta G"},{"Start":"08:08.603 ","End":"08:12.560","Text":"plus plus might include any of these for a reduction in entropy."},{"Start":"08:12.560 ","End":"08:15.320","Text":"The solvation shell of hydration bonded water that surrounds and"},{"Start":"08:15.320 ","End":"08:17.960","Text":"helps to stabilize most biomolecules in aqueous solution,"},{"Start":"08:17.960 ","End":"08:20.240","Text":"which is what is found in cells."},{"Start":"08:20.240 ","End":"08:23.180","Text":"The distortion of substrates that must occur in many reactions."},{"Start":"08:23.180 ","End":"08:27.055","Text":"By the way, this is also found in the interstitial spaces between the cells."},{"Start":"08:27.055 ","End":"08:30.170","Text":"Three, the distortion of substrates that must occur in many reactions"},{"Start":"08:30.170 ","End":"08:33.545","Text":"and the need for proper alignment of catalytic functional groups on the enzyme."},{"Start":"08:33.545 ","End":"08:36.740","Text":"Binding energy can be used to overcome all these barriers."},{"Start":"08:36.740 ","End":"08:40.880","Text":"Again, binding energy as found in this active site where"},{"Start":"08:40.880 ","End":"08:45.110","Text":"the substrate fits within the enzyme or as seen here in the enzyme and substrate,"},{"Start":"08:45.110 ","End":"08:48.729","Text":"even if it\u0027s not in a sequestration pocket like this."},{"Start":"08:48.729 ","End":"08:51.350","Text":"These interactions like hydrogen bonding as"},{"Start":"08:51.350 ","End":"08:54.335","Text":"seen here are ionic and hydrophobic interactions, etc."},{"Start":"08:54.335 ","End":"08:57.245","Text":"These can help overcome these barriers."},{"Start":"08:57.245 ","End":"08:59.450","Text":"Now, there\u0027s more to talk about,"},{"Start":"08:59.450 ","End":"09:02.240","Text":"the things that are required for an enzymatic reaction to occur,"},{"Start":"09:02.240 ","End":"09:06.080","Text":"and we will expand on this further in the next part."},{"Start":"09:06.080 ","End":"09:08.570","Text":"At this point, by the end of this part of this section,"},{"Start":"09:08.570 ","End":"09:11.870","Text":"you should understand the significance of binding energy"},{"Start":"09:11.870 ","End":"09:16.175","Text":"better and what is needed for an enzymatic reaction to occur and as said,"},{"Start":"09:16.175 ","End":"09:18.695","Text":"we covered this part,"},{"Start":"09:18.695 ","End":"09:23.250","Text":"but we\u0027ll expand on this further in Part II."}],"ID":30135},{"Watched":false,"Name":"Binding Energy Part 2","Duration":"6m 6s","ChapterTopicVideoID":28607,"CourseChapterTopicPlaylistID":286643,"HasSubtitles":true,"ThumbnailPath":null,"UploadDate":null,"DurationForVideoObject":null,"Description":null,"MetaTitle":null,"MetaDescription":null,"Canonical":null,"VideoComments":[],"Subtitles":[{"Start":"00:00.000 ","End":"00:03.015","Text":"Welcome back to binding energy,"},{"Start":"00:03.015 ","End":"00:08.530","Text":"we are within Part 2 and we will expand on the significance of binding energy,"},{"Start":"00:08.530 ","End":"00:10.765","Text":"what is needed for an enzymatic reaction to occur,"},{"Start":"00:10.765 ","End":"00:17.125","Text":"and expand on the idea of the induced fit model and how it relates to these concepts."},{"Start":"00:17.125 ","End":"00:24.075","Text":"Now we ended Part 1 by mentioning things that need to occur,"},{"Start":"00:24.075 ","End":"00:28.240","Text":"barriers that need to be overcome in order for a reaction to occur,"},{"Start":"00:28.240 ","End":"00:32.225","Text":"and we now go into how enzymes enabled reactions."},{"Start":"00:32.225 ","End":"00:36.085","Text":"Let\u0027s further elaborate on these ideas."},{"Start":"00:36.085 ","End":"00:39.010","Text":"Now first, a large restriction in"},{"Start":"00:39.010 ","End":"00:43.040","Text":"the relative motions of 2 substrates that are to react,"},{"Start":"00:43.040 ","End":"00:48.740","Text":"or entropy reduction is 1 obvious benefit of binding them to an enzyme."},{"Start":"00:48.740 ","End":"00:53.315","Text":"If you have 2 substrates and they fit specifically in the active site,"},{"Start":"00:53.315 ","End":"00:56.720","Text":"this 1 fits here, this 1 fits here."},{"Start":"00:56.720 ","End":"01:02.030","Text":"It results in them being brought closely together"},{"Start":"01:02.030 ","End":"01:07.880","Text":"and their motion is restricted by this binding,"},{"Start":"01:07.880 ","End":"01:10.340","Text":"this interaction and the entropy,"},{"Start":"01:10.340 ","End":"01:12.285","Text":"their freedom is reduced."},{"Start":"01:12.285 ","End":"01:14.405","Text":"There\u0027s a reduction in energy,"},{"Start":"01:14.405 ","End":"01:18.035","Text":"reduction in their motion and they\u0027re closer together,"},{"Start":"01:18.035 ","End":"01:23.585","Text":"it makes it easier so that the reaction can take place."},{"Start":"01:23.585 ","End":"01:27.290","Text":"Binding energy holds the substrates in"},{"Start":"01:27.290 ","End":"01:29.690","Text":"the proper orientation to react based on"},{"Start":"01:29.690 ","End":"01:32.980","Text":"that active site and the way they fit and attract."},{"Start":"01:32.980 ","End":"01:36.650","Text":"A substantial contribution to catalysis because"},{"Start":"01:36.650 ","End":"01:40.985","Text":"productive collisions between molecules in solution can be exceedingly rare,"},{"Start":"01:40.985 ","End":"01:43.265","Text":"by having this occur,"},{"Start":"01:43.265 ","End":"01:45.635","Text":"they are now close to each other."},{"Start":"01:45.635 ","End":"01:48.230","Text":"Substrates can be precisely aligned on"},{"Start":"01:48.230 ","End":"01:51.350","Text":"the enzyme with many weak interactions between each substrate"},{"Start":"01:51.350 ","End":"01:54.710","Text":"and strategically located groups on the enzyme"},{"Start":"01:54.710 ","End":"01:58.745","Text":"clamping the substrate molecules into the proper positions."},{"Start":"01:58.745 ","End":"02:02.420","Text":"Studies have shown that constraining the motion of"},{"Start":"02:02.420 ","End":"02:07.495","Text":"2 reactants can produce written enhancements of many orders of magnitude."},{"Start":"02:07.495 ","End":"02:10.490","Text":"Just this factor right here is"},{"Start":"02:10.490 ","End":"02:16.790","Text":"a great contribution to the ability of enzymes to catalyze reactions."},{"Start":"02:16.790 ","End":"02:20.210","Text":"Second, formation of weak bonds between substrate and"},{"Start":"02:20.210 ","End":"02:24.740","Text":"enzyme also results in the salvation of the substrate."},{"Start":"02:24.740 ","End":"02:28.640","Text":"Enzyme substrate interactions replace most or all of"},{"Start":"02:28.640 ","End":"02:32.985","Text":"the hydrogen bonds between the substrate in water,"},{"Start":"02:32.985 ","End":"02:38.585","Text":"if these are hydrogen bonds between substrates in water that allows their interaction,"},{"Start":"02:38.585 ","End":"02:42.200","Text":"once the enzyme and the substrate come close together and"},{"Start":"02:42.200 ","End":"02:45.980","Text":"then water is displaced by the enzyme substrate interaction,"},{"Start":"02:45.980 ","End":"02:48.660","Text":"and these interactions are replaced."},{"Start":"02:48.880 ","End":"02:53.765","Text":"What happens, these water molecules are pushed aside,"},{"Start":"02:53.765 ","End":"02:57.800","Text":"and what you have is enzyme-substrate interaction that is stabilized by"},{"Start":"02:57.800 ","End":"03:02.250","Text":"these hydrogen bonds and desolvation,"},{"Start":"03:02.250 ","End":"03:04.880","Text":"meaning water is moved away,"},{"Start":"03:04.880 ","End":"03:07.130","Text":"solution is moved out of the way,"},{"Start":"03:07.130 ","End":"03:11.330","Text":"occurs between and around the substrate."},{"Start":"03:11.330 ","End":"03:17.150","Text":"Third, binding energy involving weak interactions formed only in"},{"Start":"03:17.150 ","End":"03:24.065","Text":"the reaction transition state helps to compensate thermodynamically for any distortion,"},{"Start":"03:24.065 ","End":"03:31.010","Text":"primarily electron redistribution that the substrate must undergo to react."},{"Start":"03:31.010 ","End":"03:36.740","Text":"These binding energies involving the weak interactions that"},{"Start":"03:36.740 ","End":"03:39.590","Text":"occur only once the enzyme"},{"Start":"03:39.590 ","End":"03:42.770","Text":"and substrate had come together and are in the transition state,"},{"Start":"03:42.770 ","End":"03:48.380","Text":"help compensate thermodynamically for any distortion,"},{"Start":"03:48.380 ","End":"03:52.370","Text":"for any obstacle for the reaction to occur."},{"Start":"03:52.370 ","End":"03:57.290","Text":"Finally, the enzyme itself usually undergoes a change in confirmation when"},{"Start":"03:57.290 ","End":"04:02.300","Text":"the substrate binds induced by multiple weak interactions with the substrate."},{"Start":"04:02.300 ","End":"04:04.325","Text":"If we look at this figure,"},{"Start":"04:04.325 ","End":"04:05.720","Text":"you have an enzyme,"},{"Start":"04:05.720 ","End":"04:07.530","Text":"it gives us specific example here,"},{"Start":"04:07.530 ","End":"04:08.735","Text":"we don\u0027t need to get into it,"},{"Start":"04:08.735 ","End":"04:12.680","Text":"but you have an enzyme and there\u0027s the active site and then there\u0027s the substrate."},{"Start":"04:12.680 ","End":"04:14.810","Text":"The substrate comes to bind it,"},{"Start":"04:14.810 ","End":"04:16.430","Text":"but as you could see here,"},{"Start":"04:16.430 ","End":"04:23.430","Text":"it\u0027s a little rounded and it doesn\u0027t really fit this more sharp triangular."},{"Start":"04:23.430 ","End":"04:25.740","Text":"They get close together,"},{"Start":"04:25.740 ","End":"04:29.375","Text":"and when the substrate binds,"},{"Start":"04:29.375 ","End":"04:33.045","Text":"this enzyme undergoes a conformational change,"},{"Start":"04:33.045 ","End":"04:38.195","Text":"so that now you see it has changed from this roundness here,"},{"Start":"04:38.195 ","End":"04:44.543","Text":"and this roundness here to now be pointy to fit this,"},{"Start":"04:44.543 ","End":"04:47.190","Text":"and pointy to fit here."},{"Start":"04:47.190 ","End":"04:51.875","Text":"This is induced by multiple weak interactions with the substrate."},{"Start":"04:51.875 ","End":"04:56.870","Text":"This enables then in the transition state right here,"},{"Start":"04:56.870 ","End":"05:00.900","Text":"from enzyme substrate complex and enzyme product complex."},{"Start":"05:00.900 ","End":"05:03.484","Text":"If you remember from previous lessons,"},{"Start":"05:03.484 ","End":"05:10.985","Text":"this is the transition state when you have these enzyme substrate complex,"},{"Start":"05:10.985 ","End":"05:14.270","Text":"we also call them ES and enzyme product complex,"},{"Start":"05:14.270 ","End":"05:15.700","Text":"which we call the EP,"},{"Start":"05:15.700 ","End":"05:21.710","Text":"that then allows for the reaction to occur resulting in the product."},{"Start":"05:21.710 ","End":"05:25.715","Text":"Now, this is referred to as induced fit,"},{"Start":"05:25.715 ","End":"05:27.755","Text":"and we explain this previously,"},{"Start":"05:27.755 ","End":"05:29.780","Text":"now we\u0027re explaining it further."},{"Start":"05:29.780 ","End":"05:35.170","Text":"It\u0027s a mechanism postulated by Daniel Koshland in 1958."},{"Start":"05:35.170 ","End":"05:39.890","Text":"We\u0027re now going to dive further into the idea of"},{"Start":"05:39.890 ","End":"05:45.080","Text":"induced fit as postulated by Daniel Koshland in 1958,"},{"Start":"05:45.080 ","End":"05:49.040","Text":"and we will cover this in the next section."},{"Start":"05:49.040 ","End":"05:52.655","Text":"With this, we completed Part 2 of binding energy,"},{"Start":"05:52.655 ","End":"05:56.900","Text":"and you should be able to explain the significance of binding energy,"},{"Start":"05:56.900 ","End":"06:02.600","Text":"what is needed for an enzymatic reaction to occur and expand on the induced fit model."},{"Start":"06:02.600 ","End":"06:06.420","Text":"Now we\u0027re going to go into Part 3 of binding energy."}],"ID":30136},{"Watched":false,"Name":"Binding Energy Part 3","Duration":"6m 59s","ChapterTopicVideoID":28608,"CourseChapterTopicPlaylistID":286643,"HasSubtitles":true,"ThumbnailPath":null,"UploadDate":null,"DurationForVideoObject":null,"Description":null,"MetaTitle":null,"MetaDescription":null,"Canonical":null,"VideoComments":[],"Subtitles":[{"Start":"00:00.470 ","End":"00:04.080","Text":"Here we are. We\u0027re in Part III of binding energy,"},{"Start":"00:04.080 ","End":"00:08.460","Text":"but then at this section you\u0027ll be able to comprehend induced fit,"},{"Start":"00:08.570 ","End":"00:13.140","Text":"a mechanism postulated by Daniel Koshland in 1958."},{"Start":"00:13.140 ","End":"00:16.500","Text":"This is what we summed up at the end of the previous part."},{"Start":"00:16.500 ","End":"00:19.170","Text":"We have this figure that illustrates"},{"Start":"00:19.170 ","End":"00:22.935","Text":"the induced fit with the idea of a substrate coming to interact"},{"Start":"00:22.935 ","End":"00:29.970","Text":"with an enzyme entering the active site resulting in a change in the enzyme conformation."},{"Start":"00:29.970 ","End":"00:32.760","Text":"There\u0027s a slight change in the shape"},{"Start":"00:32.760 ","End":"00:37.510","Text":"as the substrate binds and then you get the enzyme substrate complex."},{"Start":"00:38.180 ","End":"00:41.130","Text":"It shows here some water being added,"},{"Start":"00:41.130 ","End":"00:44.045","Text":"you then have the enzyme product complex."},{"Start":"00:44.045 ","End":"00:49.745","Text":"This all occurs within the transition state of the reaction."},{"Start":"00:49.745 ","End":"00:53.060","Text":"Then, once you\u0027ve gone through the transition state,"},{"Start":"00:53.060 ","End":"00:55.219","Text":"you result in the enzyme releasing"},{"Start":"00:55.219 ","End":"00:58.340","Text":"the actual product and the product leaves the active site."},{"Start":"00:58.340 ","End":"01:02.360","Text":"Induced fit serves to bring specific functional groups on"},{"Start":"01:02.360 ","End":"01:06.515","Text":"the enzyme into the proper position to catalyze the reaction."},{"Start":"01:06.515 ","End":"01:09.500","Text":"The conformational change also permits formation of"},{"Start":"01:09.500 ","End":"01:13.415","Text":"additional weak bonding interactions in the transition state,"},{"Start":"01:13.415 ","End":"01:15.545","Text":"and this as we mentioned,"},{"Start":"01:15.545 ","End":"01:17.465","Text":"is the transition state right here,"},{"Start":"01:17.465 ","End":"01:22.445","Text":"is very important for this reaction for this process to occur."},{"Start":"01:22.445 ","End":"01:26.900","Text":"In either case, the new enzyme conformation has enhanced catalytic properties."},{"Start":"01:26.900 ","End":"01:30.050","Text":"As we\u0027ve seen, induced fit is a common feature of"},{"Start":"01:30.050 ","End":"01:33.740","Text":"the reversible binding of ligands to proteins."},{"Start":"01:33.740 ","End":"01:37.805","Text":"You remember, even though we\u0027re seeing the arrow here going this way, actually,"},{"Start":"01:37.805 ","End":"01:43.535","Text":"we had talked about previously that these can be reversible."},{"Start":"01:43.535 ","End":"01:46.310","Text":"An induced fit is also important in"},{"Start":"01:46.310 ","End":"01:51.080","Text":"the interaction of almost every enzyme with its substrate."},{"Start":"01:51.080 ","End":"01:55.410","Text":"This idea of the induced fit,"},{"Start":"01:55.410 ","End":"01:58.835","Text":"the 2 things that don\u0027t match perfectly,"},{"Start":"01:58.835 ","End":"02:01.190","Text":"come together and when they come together,"},{"Start":"02:01.190 ","End":"02:04.680","Text":"then they adjust to perfectly match each other,"},{"Start":"02:04.680 ","End":"02:11.410","Text":"and it\u0027s the enzyme that changes its conformation is a very important one."},{"Start":"02:11.410 ","End":"02:14.310","Text":"You can think of the analogy is romantic,"},{"Start":"02:14.310 ","End":"02:20.585","Text":"2 people coming together or a previous section I mentioned the idea of a confirmation"},{"Start":"02:20.585 ","End":"02:27.395","Text":"of the special conforming mattresses that are flat yet when you lie down on them,"},{"Start":"02:27.395 ","End":"02:31.745","Text":"they adjust to your shape and hug you."},{"Start":"02:31.745 ","End":"02:35.840","Text":"They hug you while you\u0027re sleeping and fit you"},{"Start":"02:35.840 ","End":"02:40.145","Text":"completely yet before you place your body weight on them,"},{"Start":"02:40.145 ","End":"02:41.755","Text":"they were just flat."},{"Start":"02:41.755 ","End":"02:48.050","Text":"This suggestion that Daniel Koshland made as a mechanism aside from the lock and key,"},{"Start":"02:48.050 ","End":"02:50.750","Text":"was a very important revelation,"},{"Start":"02:50.750 ","End":"02:52.760","Text":"a very important idea."},{"Start":"02:52.760 ","End":"02:57.650","Text":"Now let\u0027s summarize what we talked about with regard to how enzymes work,"},{"Start":"02:57.650 ","End":"02:58.940","Text":"because we covered a lot of"},{"Start":"02:58.940 ","End":"03:03.125","Text":"different things and there\u0027s a lot of things to remember and understand."},{"Start":"03:03.125 ","End":"03:06.320","Text":"Enzymes are highly effective catalysts,"},{"Start":"03:06.320 ","End":"03:12.380","Text":"commonly enhancing reaction rates by a factor of 10^5 or 10^17."},{"Start":"03:12.380 ","End":"03:14.085","Text":"This is a lot."},{"Start":"03:14.085 ","End":"03:16.100","Text":"10^2 is 100,"},{"Start":"03:16.100 ","End":"03:17.600","Text":"10^6 is a million,"},{"Start":"03:17.600 ","End":"03:22.310","Text":"10^5 is 100,000 or 10^17."},{"Start":"03:22.310 ","End":"03:29.660","Text":"This is really significant enhancement in a rate of a reaction."},{"Start":"03:29.660 ","End":"03:34.340","Text":"Enzyme catalyzed reactions are characterized by the formation of a complex"},{"Start":"03:34.340 ","End":"03:39.050","Text":"between substrate and enzyme and ES complex as seen here."},{"Start":"03:39.050 ","End":"03:40.640","Text":"This is the ES complex,"},{"Start":"03:40.640 ","End":"03:44.580","Text":"enzyme substrate complex, ES complex."},{"Start":"03:44.580 ","End":"03:47.570","Text":"This is it right here with the substrate"},{"Start":"03:47.570 ","End":"03:51.665","Text":"binding occurring in a pocket on the enzyme called the active site."},{"Start":"03:51.665 ","End":"03:54.260","Text":"The substrate binds this pocket,"},{"Start":"03:54.260 ","End":"03:58.730","Text":"the active site, and you have the enzyme substrate complex."},{"Start":"03:58.730 ","End":"04:03.430","Text":"The function of enzymes and other catalysts is to lower the activation energy,"},{"Start":"04:03.430 ","End":"04:06.590","Text":"which is this area,"},{"Start":"04:06.590 ","End":"04:12.230","Text":"so it\u0027s Delta G plus plus and also we had seen it marked as EA activation energy,"},{"Start":"04:12.230 ","End":"04:14.120","Text":"the energy of activation for reaction,"},{"Start":"04:14.120 ","End":"04:17.570","Text":"and thereby it enhances the reaction rate"},{"Start":"04:17.570 ","End":"04:21.200","Text":"because the minute you have lower activation energy,"},{"Start":"04:21.200 ","End":"04:24.635","Text":"you need to invest less energy for the reaction to occur."},{"Start":"04:24.635 ","End":"04:26.660","Text":"It can happen faster."},{"Start":"04:26.660 ","End":"04:30.035","Text":"Talked about pushing a boulder up a hill."},{"Start":"04:30.035 ","End":"04:31.985","Text":"If it\u0027s a smaller hill,"},{"Start":"04:31.985 ","End":"04:33.499","Text":"it will be easier,"},{"Start":"04:33.499 ","End":"04:35.675","Text":"less energy investment, less time,"},{"Start":"04:35.675 ","End":"04:38.750","Text":"and the reaction will occur faster than if you have to"},{"Start":"04:38.750 ","End":"04:42.280","Text":"push that boulder all the way up this huge hill."},{"Start":"04:42.280 ","End":"04:49.400","Text":"A key thing to remind you is the equilibrium of a reaction is unaffected by the enzyme."},{"Start":"04:49.400 ","End":"04:52.340","Text":"A significant part of the energy used for"},{"Start":"04:52.340 ","End":"04:56.630","Text":"enzymatic rate enhancement is derived from weak interactions,"},{"Start":"04:56.630 ","End":"04:59.180","Text":"and these include hydrogen bonds and hydrophobic and"},{"Start":"04:59.180 ","End":"05:02.525","Text":"ionic interactions between substrate and enzyme."},{"Start":"05:02.525 ","End":"05:05.600","Text":"The enzyme active site is structured so that some of"},{"Start":"05:05.600 ","End":"05:10.265","Text":"these weak interactions occur preferentially in the reaction transition state,"},{"Start":"05:10.265 ","End":"05:13.115","Text":"thus stabilizing the transition state,"},{"Start":"05:13.115 ","End":"05:16.475","Text":"and thus pushing the reaction forward."},{"Start":"05:16.475 ","End":"05:21.500","Text":"The need for multiple interactions is 1 reason for the large size of enzyme,"},{"Start":"05:21.500 ","End":"05:24.170","Text":"because these interactions on their own,"},{"Start":"05:24.170 ","End":"05:25.445","Text":"these weak interactions,"},{"Start":"05:25.445 ","End":"05:28.395","Text":"only contribute a small amount of energy."},{"Start":"05:28.395 ","End":"05:30.875","Text":"We talked about the 4-30 kilojoules per mole,"},{"Start":"05:30.875 ","End":"05:35.210","Text":"yet multiple allowed to overcome the need for"},{"Start":"05:35.210 ","End":"05:39.765","Text":"more investment of energy to overcome the activation energy barrier."},{"Start":"05:39.765 ","End":"05:42.380","Text":"The binding energy, Delta G_B,"},{"Start":"05:42.380 ","End":"05:48.379","Text":"can be used to lower substrate entropy or to cause a conformational change in the enzyme."},{"Start":"05:48.379 ","End":"05:50.945","Text":"This is going back to the induced fit."},{"Start":"05:50.945 ","End":"05:53.435","Text":"This binding energy right here,"},{"Start":"05:53.435 ","End":"05:55.280","Text":"this Delta G_B,"},{"Start":"05:55.280 ","End":"05:59.495","Text":"the binding of the enzyme to substrate,"},{"Start":"05:59.495 ","End":"06:02.965","Text":"can lower the substrate entropy and"},{"Start":"06:02.965 ","End":"06:08.775","Text":"result in this smaller activation energy that\u0027s needed."},{"Start":"06:08.775 ","End":"06:14.825","Text":"It also can cause a conformational change in the enzyme resulting in the induced fit,"},{"Start":"06:14.825 ","End":"06:18.905","Text":"which results in the lower activation energy."},{"Start":"06:18.905 ","End":"06:23.660","Text":"Binding energy also accounts for the exquisite specificity of enzymes for"},{"Start":"06:23.660 ","End":"06:26.870","Text":"their substrates because specific residues"},{"Start":"06:26.870 ","End":"06:29.420","Text":"interact and bind with other specific residues."},{"Start":"06:29.420 ","End":"06:32.450","Text":"Therefore, the specific substrate will interact with"},{"Start":"06:32.450 ","End":"06:36.200","Text":"a specific residues in the active site of the enzymes."},{"Start":"06:36.200 ","End":"06:39.320","Text":"It\u0027s not only helping in reducing the activation energy,"},{"Start":"06:39.320 ","End":"06:43.180","Text":"it also contributes to the specificity."},{"Start":"06:43.180 ","End":"06:47.540","Text":"With this, we completed the section of binding energy."},{"Start":"06:47.540 ","End":"06:52.415","Text":"By now you should be able to understand the significance of binding energy,"},{"Start":"06:52.415 ","End":"06:54.965","Text":"what is needed for an enzymatic reaction to occur,"},{"Start":"06:54.965 ","End":"06:59.340","Text":"and understand the concept of induced fit."}],"ID":30137},{"Watched":false,"Name":"Exercise 10","Duration":"2m 31s","ChapterTopicVideoID":28623,"CourseChapterTopicPlaylistID":286643,"HasSubtitles":true,"ThumbnailPath":null,"UploadDate":null,"DurationForVideoObject":null,"Description":null,"MetaTitle":null,"MetaDescription":null,"Canonical":null,"VideoComments":[],"Subtitles":[{"Start":"00:00.000 ","End":"00:02.610","Text":"We\u0027ve completed this section on binding energy."},{"Start":"00:02.610 ","End":"00:04.785","Text":"Now, we\u0027re going to test our knowledge."},{"Start":"00:04.785 ","End":"00:09.165","Text":"Part 1, what can be said about the binding energy of an enzyme?"},{"Start":"00:09.165 ","End":"00:12.330","Text":"We mentioned 2 main things in the lesson."},{"Start":"00:12.330 ","End":"00:14.250","Text":"First one is discussed in the previous lesson,"},{"Start":"00:14.250 ","End":"00:16.095","Text":"the second covered in this lesson."},{"Start":"00:16.095 ","End":"00:18.420","Text":"The same binding energy that provides energy for"},{"Start":"00:18.420 ","End":"00:21.420","Text":"catalysis also gives an enzyme it\u0027s specificity,"},{"Start":"00:21.420 ","End":"00:25.800","Text":"the ability to discriminate between a substrate and a competing molecule."},{"Start":"00:25.800 ","End":"00:31.740","Text":"Binding energy of an enzyme allows catalysis of a reaction,"},{"Start":"00:31.740 ","End":"00:36.635","Text":"as well as specificity of an enzyme to its substrate."},{"Start":"00:36.635 ","End":"00:39.320","Text":"Part II, how does binding energy contribute"},{"Start":"00:39.320 ","End":"00:42.040","Text":"to the functions mentioned in Part 1 of the question?"},{"Start":"00:42.040 ","End":"00:45.055","Text":"As for binding energy providing energy for catalysis,"},{"Start":"00:45.055 ","End":"00:47.585","Text":"this was explained in the previous lesson and"},{"Start":"00:47.585 ","End":"00:51.095","Text":"re-iterated and expanded on in this lesson to detail"},{"Start":"00:51.095 ","End":"00:53.510","Text":"that the energy available for formation of"},{"Start":"00:53.510 ","End":"00:58.295","Text":"a single weak interaction is generally estimated to be 4-30 kilojoules per mole."},{"Start":"00:58.295 ","End":"01:00.680","Text":"The overall energy from"},{"Start":"01:00.680 ","End":"01:05.840","Text":"several such interactions is therefore sufficient to lower activation energy by"},{"Start":"01:05.840 ","End":"01:09.950","Text":"the 60-100 kilo joules per mole required to explain"},{"Start":"01:09.950 ","End":"01:14.510","Text":"the large rate enhancements observed for enzymes."},{"Start":"01:14.510 ","End":"01:17.300","Text":"This is observed for many enzymes."},{"Start":"01:17.300 ","End":"01:20.015","Text":"With regard to enzyme specificity,"},{"Start":"01:20.015 ","End":"01:23.450","Text":"if an enzyme active site has functional groups arranged optimally to"},{"Start":"01:23.450 ","End":"01:27.100","Text":"form a variety of weak interactions with a particular substrate,"},{"Start":"01:27.100 ","End":"01:28.580","Text":"in the transition state,"},{"Start":"01:28.580 ","End":"01:33.980","Text":"the enzyme will not be able to interact to the same degree with any other molecule."},{"Start":"01:33.980 ","End":"01:37.325","Text":"It will be somewhat specific and selective."},{"Start":"01:37.325 ","End":"01:40.910","Text":"For example, if the substrate has a hydroxyl group that forms"},{"Start":"01:40.910 ","End":"01:45.005","Text":"a hydrogen bond with a specific glue residue on the enzyme,"},{"Start":"01:45.005 ","End":"01:49.670","Text":"any molecule lacking a hydroxyl group at that particular position will be"},{"Start":"01:49.670 ","End":"01:56.020","Text":"a poor substrate for the enzyme and therefore will not interact to the same degree."},{"Start":"01:56.020 ","End":"02:00.695","Text":"This enzyme and specific substrate with the hydroxyl group"},{"Start":"02:00.695 ","End":"02:05.675","Text":"will be the ones bound and have a reaction occur."},{"Start":"02:05.675 ","End":"02:09.080","Text":"In addition, any molecule with an extra functional group"},{"Start":"02:09.080 ","End":"02:12.725","Text":"for which the enzyme has no pocket or binding site"},{"Start":"02:12.725 ","End":"02:16.070","Text":"is likely to be excluded from the enzyme because it won\u0027t"},{"Start":"02:16.070 ","End":"02:20.120","Text":"have the affinity to interact with the enzyme."},{"Start":"02:20.120 ","End":"02:24.095","Text":"In general, specificity is derived from the formation of"},{"Start":"02:24.095 ","End":"02:30.810","Text":"many weak interactions between the enzyme and its specific substrate molecule."}],"ID":30138},{"Watched":false,"Name":"Exercise 11","Duration":"3m 9s","ChapterTopicVideoID":28602,"CourseChapterTopicPlaylistID":286643,"HasSubtitles":true,"ThumbnailPath":null,"UploadDate":null,"DurationForVideoObject":null,"Description":null,"MetaTitle":null,"MetaDescription":null,"Canonical":null,"VideoComments":[],"Subtitles":[{"Start":"00:00.000 ","End":"00:03.375","Text":"We have another exercise about binding energy."},{"Start":"00:03.375 ","End":"00:06.210","Text":"Part 1, which statement is false?"},{"Start":"00:06.210 ","End":"00:09.960","Text":"A, more than 80% of the enzymatic rate acceleration has been traced to"},{"Start":"00:09.960 ","End":"00:14.970","Text":"enzyme-substrate interactions involving the phosphate group on carbon 3 of the substrate."},{"Start":"00:14.970 ","End":"00:18.875","Text":"B, a given enzyme might incorporate several types of mechanisms,"},{"Start":"00:18.875 ","End":"00:20.680","Text":"which are not mutually exclusive,"},{"Start":"00:20.680 ","End":"00:24.990","Text":"that yield the reaction rate accelerations overall mechanism of action."},{"Start":"00:24.990 ","End":"00:27.270","Text":"C, for most enzymes,"},{"Start":"00:27.270 ","End":"00:30.630","Text":"it\u0027s difficult to quantify the contribution of any one catalytic mechanism to"},{"Start":"00:30.630 ","End":"00:34.935","Text":"the rate and or specificity of a particular enzyme catalyzed reaction."},{"Start":"00:34.935 ","End":"00:37.260","Text":"D, binding energy makes an important,"},{"Start":"00:37.260 ","End":"00:42.660","Text":"yet mostly small and lesser, contribution to catalysis."},{"Start":"00:42.880 ","End":"00:46.400","Text":"Let\u0027s talk about this one at a time."},{"Start":"00:46.400 ","End":"00:50.420","Text":"More than 80% of the enzymatic rate acceleration has been"},{"Start":"00:50.420 ","End":"00:52.460","Text":"traced to enzyme substrate interactions"},{"Start":"00:52.460 ","End":"00:54.995","Text":"involving the phosphate group on carbon 3 of the substrate."},{"Start":"00:54.995 ","End":"00:57.050","Text":"We mentioned this sentence."},{"Start":"00:57.050 ","End":"01:01.700","Text":"We didn\u0027t elaborate on the specifics of the chemistry of this too much."},{"Start":"01:01.700 ","End":"01:05.090","Text":"But this sentence was mentioned verbatim."},{"Start":"01:05.090 ","End":"01:07.220","Text":"Therefore, this is true and this can\u0027t be"},{"Start":"01:07.220 ","End":"01:10.805","Text":"our answer because we\u0027re looking for something that\u0027s false."},{"Start":"01:10.805 ","End":"01:12.815","Text":"B, a given enzyme,"},{"Start":"01:12.815 ","End":"01:17.420","Text":"might incorporate several types of mechanisms which are not mutually"},{"Start":"01:17.420 ","End":"01:23.000","Text":"exclusive that yield the reaction rate acceleration and its overall mechanism of action."},{"Start":"01:23.000 ","End":"01:24.440","Text":"What we actually mentioned a few,"},{"Start":"01:24.440 ","End":"01:28.115","Text":"we went over a few saying that these can come together,"},{"Start":"01:28.115 ","End":"01:30.005","Text":"or just a few of them,"},{"Start":"01:30.005 ","End":"01:37.440","Text":"all of them, allowing the reaction rate to be accelerated as catalyzed by the enzymes."},{"Start":"01:37.440 ","End":"01:39.470","Text":"Again, this is a true statement,"},{"Start":"01:39.470 ","End":"01:41.555","Text":"therefore, it isn\u0027t our answer."},{"Start":"01:41.555 ","End":"01:44.010","Text":"C, for most enzymes,"},{"Start":"01:44.010 ","End":"01:47.405","Text":"it\u0027s difficult to quantify the contribution of"},{"Start":"01:47.405 ","End":"01:50.090","Text":"any one catalytic mechanism to the rate and"},{"Start":"01:50.090 ","End":"01:53.530","Text":"our specificity of a particular enzyme catalyzed reaction."},{"Start":"01:53.530 ","End":"01:57.290","Text":"Again, we know that each contribution is"},{"Start":"01:57.290 ","End":"02:02.630","Text":"within a range and on its own, not necessarily enough,"},{"Start":"02:02.630 ","End":"02:04.430","Text":"but when they come together,"},{"Start":"02:04.430 ","End":"02:05.945","Text":"they are sufficient,"},{"Start":"02:05.945 ","End":"02:08.720","Text":"yet it is true that it\u0027s difficult to"},{"Start":"02:08.720 ","End":"02:12.470","Text":"quantify the contribution of any one catalytic mechanism."},{"Start":"02:12.470 ","End":"02:15.965","Text":"Therefore, this is also true and not our answer."},{"Start":"02:15.965 ","End":"02:19.835","Text":"Let\u0027s go over D and see if this is untrue."},{"Start":"02:19.835 ","End":"02:22.190","Text":"Binding energy makes an important,"},{"Start":"02:22.190 ","End":"02:26.060","Text":"yet mostly small and lesser contribution to catalysis."},{"Start":"02:26.060 ","End":"02:32.155","Text":"We\u0027ll actually binding energy makes a great contribution to catalysis."},{"Start":"02:32.155 ","End":"02:35.193","Text":"Also mentioned to specificity."},{"Start":"02:35.193 ","End":"02:37.630","Text":"This is a false statement,"},{"Start":"02:37.630 ","End":"02:40.475","Text":"and therefore this is our answer."},{"Start":"02:40.475 ","End":"02:44.135","Text":"Part 2, correct the false statement from Part 1."},{"Start":"02:44.135 ","End":"02:46.460","Text":"Well, we said that A, B,"},{"Start":"02:46.460 ","End":"02:49.965","Text":"and C are correct, while D was incorrect."},{"Start":"02:49.965 ","End":"02:51.770","Text":"D, binding energy makes an important yet"},{"Start":"02:51.770 ","End":"02:54.130","Text":"mostly small unless your contribution to catalysis."},{"Start":"02:54.130 ","End":"02:56.225","Text":"We said that it isn\u0027t small."},{"Start":"02:56.225 ","End":"02:57.725","Text":"Therefore, to correct it,"},{"Start":"02:57.725 ","End":"03:00.620","Text":"we can say binding energy makes an important and actually, most of the time,"},{"Start":"03:00.620 ","End":"03:05.400","Text":"the dominant contribution to catalysis."}],"ID":30139},{"Watched":false,"Name":"Exercise 12","Duration":"1m 24s","ChapterTopicVideoID":28603,"CourseChapterTopicPlaylistID":286643,"HasSubtitles":true,"ThumbnailPath":null,"UploadDate":null,"DurationForVideoObject":null,"Description":null,"MetaTitle":null,"MetaDescription":null,"Canonical":null,"VideoComments":[],"Subtitles":[{"Start":"00:00.000 ","End":"00:02.385","Text":"We\u0027re within binding energy,"},{"Start":"00:02.385 ","End":"00:05.040","Text":"testing our knowledge with exercises."},{"Start":"00:05.040 ","End":"00:07.710","Text":"4 specific barriers were mentioned as needed to"},{"Start":"00:07.710 ","End":"00:10.500","Text":"be overcome in order for a reaction to occur."},{"Start":"00:10.500 ","End":"00:12.690","Text":"State at least 2 of these."},{"Start":"00:12.690 ","End":"00:16.320","Text":"Prominent physical and thermodynamic factors contributing to Delta G++,"},{"Start":"00:16.320 ","End":"00:17.670","Text":"the activation barrier,"},{"Start":"00:17.670 ","End":"00:21.915","Text":"the barrier of reaction might include 1,"},{"Start":"00:21.915 ","End":"00:23.610","Text":"a reduction in entropy in the form of"},{"Start":"00:23.610 ","End":"00:26.415","Text":"decreased freedom of motion of 2 molecules in solution."},{"Start":"00:26.415 ","End":"00:30.570","Text":"Remember, entropy means freedom of motion, randomness."},{"Start":"00:30.570 ","End":"00:33.980","Text":"Reducing this allows a higher ability"},{"Start":"00:33.980 ","End":"00:37.430","Text":"of 2 molecules to come together and interact in a solution."},{"Start":"00:37.430 ","End":"00:41.000","Text":"2, the solvation shell of hydrogen-bonded water that"},{"Start":"00:41.000 ","End":"00:44.870","Text":"surrounds and helps to stabilize most biomolecules in aqueous solution."},{"Start":"00:44.870 ","End":"00:48.740","Text":"Hydrogen-bonded water has a solvation shell"},{"Start":"00:48.740 ","End":"00:51.050","Text":"that surrounds molecules and if you remember from"},{"Start":"00:51.050 ","End":"00:53.540","Text":"the lecture we had the figures showing this and it helps"},{"Start":"00:53.540 ","End":"00:57.175","Text":"stabilize most biomolecules in aqueous solution."},{"Start":"00:57.175 ","End":"01:00.230","Text":"3, the distortion of substrates that must"},{"Start":"01:00.230 ","End":"01:03.529","Text":"occur in many reactions primarily electron redistribution,"},{"Start":"01:03.529 ","End":"01:08.135","Text":"that the substrate must undergo to react and stabilize the interaction between"},{"Start":"01:08.135 ","End":"01:13.835","Text":"the substrate and enzyme is also an important aspect."},{"Start":"01:13.835 ","End":"01:19.190","Text":"4, the need for proper alignment of catalytic functional groups on the enzyme."},{"Start":"01:19.190 ","End":"01:24.270","Text":"Binding energy can be used to overcome any and all of these barriers."}],"ID":30140},{"Watched":false,"Name":"Exercise 13","Duration":"2m 8s","ChapterTopicVideoID":28604,"CourseChapterTopicPlaylistID":286643,"HasSubtitles":true,"ThumbnailPath":null,"UploadDate":null,"DurationForVideoObject":null,"Description":null,"MetaTitle":null,"MetaDescription":null,"Canonical":null,"VideoComments":[],"Subtitles":[{"Start":"00:00.140 ","End":"00:03.180","Text":"What did we learn about binding energy?"},{"Start":"00:03.180 ","End":"00:05.760","Text":"What needs to occur for a reaction to take place that is"},{"Start":"00:05.760 ","End":"00:09.720","Text":"enabled by the binding energy of enzyme and substrate?"},{"Start":"00:09.720 ","End":"00:12.675","Text":"Four of these were mentioned. So the answer."},{"Start":"00:12.675 ","End":"00:14.715","Text":"Binding energy can be used to overcome"},{"Start":"00:14.715 ","End":"00:18.960","Text":"all these barriers as explained by the following four points."},{"Start":"00:18.960 ","End":"00:25.200","Text":"First, a large restriction in the relative motion of 2 substrates that are to"},{"Start":"00:25.200 ","End":"00:31.905","Text":"react or entropy reduction is one obvious benefit of binding them to an enzyme."},{"Start":"00:31.905 ","End":"00:36.155","Text":"Binding energy holds the substrates in the proper orientation to"},{"Start":"00:36.155 ","End":"00:41.390","Text":"react a substantial contribution to catalysis that is done by enzymes,"},{"Start":"00:41.390 ","End":"00:46.355","Text":"because productive collisions between molecules in solution to be exceedingly rare."},{"Start":"00:46.355 ","End":"00:49.550","Text":"Substrates can be precisely aligned on the enzyme with"},{"Start":"00:49.550 ","End":"00:51.620","Text":"many weak interactions between each substrate and"},{"Start":"00:51.620 ","End":"00:54.365","Text":"strategically located groups on the enzyme,"},{"Start":"00:54.365 ","End":"00:56.270","Text":"clamping the substrate molecules into"},{"Start":"00:56.270 ","End":"01:00.670","Text":"the proper positions as shown in the figures in the lesson."},{"Start":"01:00.670 ","End":"01:05.900","Text":"Studies have shown this and effectively also shown that constraining"},{"Start":"01:05.900 ","End":"01:11.465","Text":"the motion of 2 reactants can produce rate enhancements of many orders of magnitude."},{"Start":"01:11.465 ","End":"01:14.810","Text":"Second, formation of weak bonds between"},{"Start":"01:14.810 ","End":"01:18.530","Text":"substrate and enzyme also results in desolvation of the substrate."},{"Start":"01:18.530 ","End":"01:23.240","Text":"This means the water molecules being moved away and"},{"Start":"01:23.240 ","End":"01:28.745","Text":"the substrate and enzyme having weak bonds between them as they come closer together."},{"Start":"01:28.745 ","End":"01:33.530","Text":"Third, binding energy involving weak interactions formed only in"},{"Start":"01:33.530 ","End":"01:39.200","Text":"the reaction transition state helps to compensate thermodynamically for any distortion."},{"Start":"01:39.200 ","End":"01:41.240","Text":"We had mentioned that there are distortions and"},{"Start":"01:41.240 ","End":"01:45.590","Text":"electrons rearrangements or what not within the substrate."},{"Start":"01:45.590 ","End":"01:51.935","Text":"The binding energy can compensate for these distortions and changes."},{"Start":"01:51.935 ","End":"01:55.010","Text":"Finally, the enzyme itself usually"},{"Start":"01:55.010 ","End":"01:57.780","Text":"undergoes a change in conformation when the substrate binds,"},{"Start":"01:57.780 ","End":"02:00.965","Text":"induced by multiple weak interactions with the substrate."},{"Start":"02:00.965 ","End":"02:06.420","Text":"This is referred to as induced-fit."}],"ID":30141},{"Watched":false,"Name":"Exercise 14","Duration":"1m 23s","ChapterTopicVideoID":28605,"CourseChapterTopicPlaylistID":286643,"HasSubtitles":true,"ThumbnailPath":null,"UploadDate":null,"DurationForVideoObject":null,"Description":null,"MetaTitle":null,"MetaDescription":null,"Canonical":null,"VideoComments":[],"Subtitles":[{"Start":"00:00.180 ","End":"00:03.850","Text":"We have another exercise within binding energy."},{"Start":"00:03.850 ","End":"00:06.955","Text":"Explain the concept of induced fit."},{"Start":"00:06.955 ","End":"00:10.000","Text":"Induced fit describes the change in conformation and"},{"Start":"00:10.000 ","End":"00:13.315","Text":"enzyme usually undergoes when its substrate binds."},{"Start":"00:13.315 ","End":"00:18.595","Text":"This was a mechanism that was postulated by Daniel Koshland in 1958."},{"Start":"00:18.595 ","End":"00:23.590","Text":"This fit is induced by multiple weak interactions with the substrate,"},{"Start":"00:23.590 ","End":"00:25.930","Text":"meaning between the enzyme and substrate."},{"Start":"00:25.930 ","End":"00:29.590","Text":"Induced fit serves to bring specific functional groups"},{"Start":"00:29.590 ","End":"00:33.385","Text":"on the enzyme into the proper position to catalyze the reaction."},{"Start":"00:33.385 ","End":"00:36.640","Text":"The conformational change also permits formation of additional"},{"Start":"00:36.640 ","End":"00:39.835","Text":"weak of bonding interactions in the transition state,"},{"Start":"00:39.835 ","End":"00:42.930","Text":"which is important for the reaction to occur."},{"Start":"00:42.930 ","End":"00:48.650","Text":"In either case, the new enzyme conformation has enhanced catalytic properties."},{"Start":"00:48.650 ","End":"00:55.640","Text":"Induced fit is a common feature of the reversible binding of ligands to proteins."},{"Start":"00:55.640 ","End":"00:58.430","Text":"Induced fit is also important in"},{"Start":"00:58.430 ","End":"01:01.880","Text":"the interaction of almost every enzyme with its substrate"},{"Start":"01:01.880 ","End":"01:08.240","Text":"so it is a very important concept in the interactions between enzymes and substrates,"},{"Start":"01:08.240 ","End":"01:11.570","Text":"and enzymes, as catalysts for reactions."},{"Start":"01:11.570 ","End":"01:16.550","Text":"It was presented in the previous lesson as a second model for"},{"Start":"01:16.550 ","End":"01:23.040","Text":"enzyme-substrate interactions as an alternative to the lock and key model."}],"ID":30142}],"Thumbnail":null,"ID":286643},{"Name":"Enzyme Kinetics","TopicPlaylistFirstVideoID":0,"Duration":null,"Videos":[{"Watched":false,"Name":"Intro to Enzyme Kinetics Part 1","Duration":"7m 9s","ChapterTopicVideoID":28592,"CourseChapterTopicPlaylistID":286644,"HasSubtitles":true,"ThumbnailPath":null,"UploadDate":null,"DurationForVideoObject":null,"Description":null,"MetaTitle":null,"MetaDescription":null,"Canonical":null,"VideoComments":[],"Subtitles":[{"Start":"00:00.000 ","End":"00:01.485","Text":"Welcome to enzymes."},{"Start":"00:01.485 ","End":"00:04.260","Text":"We are within intro to enzyme kinetics."},{"Start":"00:04.260 ","End":"00:06.120","Text":"By the end of this section, you\u0027ll be able to"},{"Start":"00:06.120 ","End":"00:08.820","Text":"understand kinetics of enzyme catalyzed reactions,"},{"Start":"00:08.820 ","End":"00:10.890","Text":"describe the theory of enzyme action,"},{"Start":"00:10.890 ","End":"00:12.945","Text":"and define steady-state kinetics."},{"Start":"00:12.945 ","End":"00:15.795","Text":"We\u0027re going to split this into 2 sections."},{"Start":"00:15.795 ","End":"00:18.465","Text":"In part 1 of this lesson,"},{"Start":"00:18.465 ","End":"00:22.605","Text":"we will focus on understanding the kinetics of enzyme-catalyzed reactions."},{"Start":"00:22.605 ","End":"00:29.010","Text":"Let\u0027s begin. Welcome back to the chapter on enzymes as we"},{"Start":"00:29.010 ","End":"00:36.185","Text":"introduce enzyme kinetics bear with me as we get into the nitty-gritty of these concepts."},{"Start":"00:36.185 ","End":"00:38.270","Text":"By the end of the section will be able to understand"},{"Start":"00:38.270 ","End":"00:40.280","Text":"kinetics of enzyme catalyzed reactions,"},{"Start":"00:40.280 ","End":"00:42.028","Text":"describe the theory of enzyme action,"},{"Start":"00:42.028 ","End":"00:44.105","Text":"and define steady-state kinetics."},{"Start":"00:44.105 ","End":"00:49.445","Text":"Enzyme kinetics, as an approach to understanding mechanism,"},{"Start":"00:49.445 ","End":"00:51.860","Text":"the central approach to studying the mechanism of"},{"Start":"00:51.860 ","End":"00:54.440","Text":"an enzyme catalyzed reaction is to determine the rate of"},{"Start":"00:54.440 ","End":"01:00.125","Text":"the reaction and how it changes in response to changes in experimental parameters,"},{"Start":"01:00.125 ","End":"01:06.045","Text":"so rate and change."},{"Start":"01:06.045 ","End":"01:12.125","Text":"This is a discipline known as enzyme kinetics."},{"Start":"01:12.125 ","End":"01:14.315","Text":"This is the oldest approach to understanding"},{"Start":"01:14.315 ","End":"01:17.650","Text":"enzyme mechanisms and remains the most important."},{"Start":"01:17.650 ","End":"01:21.515","Text":"In this topic, we will cover kinetics of enzyme-catalyzed reactions."},{"Start":"01:21.515 ","End":"01:24.473","Text":"Substrate concentration S in"},{"Start":"01:24.473 ","End":"01:28.970","Text":"square brackets affects the rate of enzyme-catalyzed reactions."},{"Start":"01:28.970 ","End":"01:32.330","Text":"A key factor affecting the rate of reaction catalyzed by an enzyme is"},{"Start":"01:32.330 ","End":"01:36.845","Text":"the concentration of substrate as depicted here."},{"Start":"01:36.845 ","End":"01:41.300","Text":"This changes during the course of the reaction and substrate is converted to product,"},{"Start":"01:41.300 ","End":"01:43.520","Text":"which makes studying it complicated."},{"Start":"01:43.520 ","End":"01:45.244","Text":"Let\u0027s introduce some concepts."},{"Start":"01:45.244 ","End":"01:50.870","Text":"Substrate concentration as depicted by S in square brackets."},{"Start":"01:50.870 ","End":"01:57.740","Text":"Remember, this designates in biochem concentration."},{"Start":"01:57.740 ","End":"02:00.620","Text":"We also have initial rate of reaction,"},{"Start":"02:00.620 ","End":"02:05.765","Text":"or initial velocity of reaction designated V_0."},{"Start":"02:05.765 ","End":"02:12.199","Text":"Then we have enzyme concentration designated E in square brackets."},{"Start":"02:12.199 ","End":"02:14.075","Text":"In a typical reaction,"},{"Start":"02:14.075 ","End":"02:17.450","Text":"the enzyme may be present in nanomolar quantities,"},{"Start":"02:17.450 ","End":"02:22.460","Text":"whereas substrate may be 5 or 6 orders of magnitude higher."},{"Start":"02:22.460 ","End":"02:28.625","Text":"Generally, we would see that this concentration"},{"Start":"02:28.625 ","End":"02:34.750","Text":"would be far greater than the enzyme concentration."},{"Start":"02:34.750 ","End":"02:39.995","Text":"Initial velocity varies by different substrate concentrations,"},{"Start":"02:39.995 ","End":"02:44.195","Text":"even when the enzyme concentration is held constant,"},{"Start":"02:44.195 ","End":"02:46.910","Text":"as can be seen in the figure."},{"Start":"02:46.910 ","End":"02:49.460","Text":"So as you look,"},{"Start":"02:49.460 ","End":"02:54.313","Text":"the initial velocity is on the y-axis,"},{"Start":"02:54.313 ","End":"02:57.230","Text":"and we see that it changes."},{"Start":"02:57.230 ","End":"03:03.440","Text":"You see a change here even though the enzyme concentration is the same,"},{"Start":"03:03.440 ","End":"03:07.945","Text":"while the substrate concentration is what is changing."},{"Start":"03:07.945 ","End":"03:10.940","Text":"Now, at relatively low concentrations of substrate,"},{"Start":"03:10.940 ","End":"03:17.840","Text":"initial velocity increases almost linearly with an increase in substrate concentration."},{"Start":"03:17.840 ","End":"03:21.605","Text":"If we\u0027re looking at this region right here,"},{"Start":"03:21.605 ","End":"03:25.625","Text":"where it\u0027s relatively low concentration of substrate,"},{"Start":"03:25.625 ","End":"03:31.490","Text":"the x-axis is substrate concentration and increases as it goes from left to right."},{"Start":"03:31.490 ","End":"03:35.165","Text":"Low concentration here, if you look at this area,"},{"Start":"03:35.165 ","End":"03:39.705","Text":"you can consider this being a linear increase."},{"Start":"03:39.705 ","End":"03:43.265","Text":"Basically, this could be considered almost"},{"Start":"03:43.265 ","End":"03:47.345","Text":"a linear increase if you look at this region right here,"},{"Start":"03:47.345 ","End":"03:51.935","Text":"drawing this line, it increases linearly."},{"Start":"03:51.935 ","End":"03:55.790","Text":"Now, basically, what we\u0027re seeing here is the effect of"},{"Start":"03:55.790 ","End":"04:01.340","Text":"substrate concentration on the initial velocity of an enzyme catalyzed reaction."},{"Start":"04:01.340 ","End":"04:04.415","Text":"At higher substrate concentrations,"},{"Start":"04:04.415 ","End":"04:07.880","Text":"the initial velocity or the reaction"},{"Start":"04:07.880 ","End":"04:10.100","Text":"velocity reaction rate increases by"},{"Start":"04:10.100 ","End":"04:15.080","Text":"smaller and smaller amounts in response to increase in substrate concentration."},{"Start":"04:15.080 ","End":"04:17.330","Text":"For looking right here,"},{"Start":"04:17.330 ","End":"04:22.355","Text":"in the higher region of the substrate concentration,"},{"Start":"04:22.355 ","End":"04:26.425","Text":"we\u0027re seeing the changes here are smaller."},{"Start":"04:26.425 ","End":"04:27.791","Text":"If we look at this point,"},{"Start":"04:27.791 ","End":"04:31.025","Text":"versus this point, versus this point, versus this point,"},{"Start":"04:31.025 ","End":"04:34.815","Text":"we look at the velocity,"},{"Start":"04:34.815 ","End":"04:37.655","Text":"so let\u0027s draw a line."},{"Start":"04:37.655 ","End":"04:40.210","Text":"This is super close,"},{"Start":"04:40.210 ","End":"04:45.505","Text":"it\u0027s almost the same velocity while for looking at substrate concentration,"},{"Start":"04:45.505 ","End":"04:47.425","Text":"there are greater differences here."},{"Start":"04:47.425 ","End":"04:51.220","Text":"If we just randomly just say this is 1,"},{"Start":"04:51.220 ","End":"04:55.740","Text":"this is 2,"},{"Start":"04:55.740 ","End":"04:57.260","Text":"3, 4, 5, 6,"},{"Start":"04:57.260 ","End":"04:58.518","Text":"7, 8, 9."},{"Start":"04:58.518 ","End":"05:04.253","Text":"For substrate concentration, you see a difference here,"},{"Start":"05:04.253 ","End":"05:06.375","Text":"1, 2,"},{"Start":"05:06.375 ","End":"05:10.855","Text":"3, 4, 5, 6."},{"Start":"05:10.855 ","End":"05:15.415","Text":"You see that basically this falls on 5.5,"},{"Start":"05:15.415 ","End":"05:19.245","Text":"5.6, 5.7, 5.75."},{"Start":"05:19.245 ","End":"05:23.510","Text":"The increases are much"},{"Start":"05:23.510 ","End":"05:29.120","Text":"smaller in response to the increase in substrate concentration versus if you look here,"},{"Start":"05:29.120 ","End":"05:34.790","Text":"4 falls a little above 5, you see,"},{"Start":"05:34.790 ","End":"05:43.039","Text":"while 3 falls below 5 and 2 falls a little before so the changes here are greater."},{"Start":"05:43.039 ","End":"05:44.330","Text":"If we\u0027re looking at 1,"},{"Start":"05:44.330 ","End":"05:46.960","Text":"it falls a little above 3."},{"Start":"05:46.960 ","End":"05:51.560","Text":"All of this is to say while here there\u0027s greater changes, I mean,"},{"Start":"05:51.560 ","End":"05:53.090","Text":"look from 0-1,"},{"Start":"05:53.090 ","End":"05:57.320","Text":"you see a jump 0-1 concentration of substrate."},{"Start":"05:57.320 ","End":"06:00.410","Text":"You see a jump to over 3."},{"Start":"06:00.410 ","End":"06:01.970","Text":"Then from 1-2,"},{"Start":"06:01.970 ","End":"06:04.271","Text":"it jumps to over 4,"},{"Start":"06:04.271 ","End":"06:06.350","Text":"and then from 2-3,"},{"Start":"06:06.350 ","End":"06:08.060","Text":"it jumps to around 5,"},{"Start":"06:08.060 ","End":"06:10.805","Text":"the jumps are getting smaller and smaller,"},{"Start":"06:10.805 ","End":"06:14.690","Text":"and as you get into the higher concentrations of substrate,"},{"Start":"06:14.690 ","End":"06:18.890","Text":"the increases in the velocity are smaller."},{"Start":"06:18.890 ","End":"06:22.880","Text":"Finally, a point is reached beyond where increases in"},{"Start":"06:22.880 ","End":"06:28.055","Text":"velocity are vanishingly small as substrate increases."},{"Start":"06:28.055 ","End":"06:29.615","Text":"As you look here,"},{"Start":"06:29.615 ","End":"06:31.630","Text":"it\u0027s almost like it\u0027s flat."},{"Start":"06:31.630 ","End":"06:33.800","Text":"It\u0027s almost a horizontal line."},{"Start":"06:33.800 ","End":"06:35.525","Text":"It\u0027s a plateau."},{"Start":"06:35.525 ","End":"06:44.090","Text":"This plateau-like initial velocity region is close to the maximum velocity, the V_max."},{"Start":"06:44.090 ","End":"06:48.860","Text":"The ES complex is the key to understanding this kinetic behavior,"},{"Start":"06:48.860 ","End":"06:56.465","Text":"and this idea was better understood further studies of the ES complex."},{"Start":"06:56.465 ","End":"06:59.060","Text":"With this, we\u0027ve completed part 1 of the introduction to"},{"Start":"06:59.060 ","End":"07:01.670","Text":"enzyme kinetics within the chapter enzymes,"},{"Start":"07:01.670 ","End":"07:06.995","Text":"and we started to work on our understanding of kinetics of enzyme-catalyzed reactions."},{"Start":"07:06.995 ","End":"07:10.140","Text":"We will continue this in part 2."}],"ID":30143},{"Watched":false,"Name":"Intro to Enzyme Kinetics Part 2","Duration":"8m 1s","ChapterTopicVideoID":28593,"CourseChapterTopicPlaylistID":286644,"HasSubtitles":true,"ThumbnailPath":null,"UploadDate":null,"DurationForVideoObject":null,"Description":null,"MetaTitle":null,"MetaDescription":null,"Canonical":null,"VideoComments":[],"Subtitles":[{"Start":"00:00.000 ","End":"00:02.370","Text":"Welcome to Part 2 of the lesson on"},{"Start":"00:02.370 ","End":"00:05.489","Text":"introduction to enzyme kinetics within the chapter of enzymes."},{"Start":"00:05.489 ","End":"00:07.800","Text":"By the end of this section, you will be able to understand"},{"Start":"00:07.800 ","End":"00:10.380","Text":"kinetics of enzyme catalyzed reactions further,"},{"Start":"00:10.380 ","End":"00:12.495","Text":"describe the theory of enzyme action,"},{"Start":"00:12.495 ","End":"00:15.000","Text":"and define steady-state kinetics."},{"Start":"00:15.000 ","End":"00:18.510","Text":"The ES complex is the key to understanding this kinetic behavior."},{"Start":"00:18.510 ","End":"00:21.735","Text":"In 1903, Victor Henn,"},{"Start":"00:21.735 ","End":"00:25.050","Text":"following the lead of Wurtz,"},{"Start":"00:25.050 ","End":"00:27.540","Text":"we mentioned in a previous lecture,"},{"Start":"00:27.540 ","End":"00:32.570","Text":"suggested that the combination of an enzyme with its substrate molecule"},{"Start":"00:32.570 ","End":"00:37.955","Text":"to form an ES complex is a necessary step in enzymatic catalysis."},{"Start":"00:37.955 ","End":"00:42.905","Text":"This idea was expanded into a general theory of"},{"Start":"00:42.905 ","End":"00:51.035","Text":"enzyme action particularly by Leonor Michaelis and Maud Menten in 1913."},{"Start":"00:51.035 ","End":"00:59.462","Text":"You have Victor Henn suggesting in 1903 that the ES complex is a necessary step and"},{"Start":"00:59.462 ","End":"01:03.470","Text":"Leonor Michaelis and Maud Menten develop this idea further"},{"Start":"01:03.470 ","End":"01:08.174","Text":"into a theory of enzyme action in 1913 so a decade later."},{"Start":"01:08.174 ","End":"01:13.730","Text":"They postulated that the enzyme first combines reversibly with its substrate to"},{"Start":"01:13.730 ","End":"01:19.625","Text":"form an enzyme substrate complex in a relatively fast reversible step as seen here,"},{"Start":"01:19.625 ","End":"01:23.690","Text":"you have the enzyme and substrate and the enzyme substrate complex,"},{"Start":"01:23.690 ","End":"01:26.330","Text":"and it\u0027s a fast reversible reaction."},{"Start":"01:26.330 ","End":"01:29.210","Text":"You have k_1 going to one direction,"},{"Start":"01:29.210 ","End":"01:33.095","Text":"k minus 1 going the reverse."},{"Start":"01:33.095 ","End":"01:38.090","Text":"The ES complex then breaks down in a slower second step."},{"Start":"01:38.090 ","End":"01:46.665","Text":"The ES breaking down to E plus P is a slower step."},{"Start":"01:46.665 ","End":"01:52.860","Text":"Now because the slower second reaction limits the rate of the overall reaction,"},{"Start":"01:52.860 ","End":"01:56.570","Text":"the overall rate of the reaction is proportional to"},{"Start":"01:56.570 ","End":"02:00.673","Text":"the concentration of the species that reacts in the second step,"},{"Start":"02:00.673 ","End":"02:04.565","Text":"that is ES, enzyme substrate."},{"Start":"02:04.565 ","End":"02:08.570","Text":"At any given instant in an enzyme-catalyzed reaction,"},{"Start":"02:08.570 ","End":"02:11.240","Text":"the enzyme exists in 2 forms,"},{"Start":"02:11.240 ","End":"02:16.415","Text":"the free form E and the combined form ES."},{"Start":"02:16.415 ","End":"02:20.120","Text":"The free form E can also be thought of as"},{"Start":"02:20.120 ","End":"02:25.325","Text":"the uncombined form E versus the combined form ES."},{"Start":"02:25.325 ","End":"02:28.447","Text":"At low substrate concentrations,"},{"Start":"02:28.447 ","End":"02:33.695","Text":"most of the enzyme is in the uncombined form E. Here,"},{"Start":"02:33.695 ","End":"02:37.880","Text":"the rate is proportional to substrate concentration"},{"Start":"02:37.880 ","End":"02:42.470","Text":"because the equilibrium is pushed toward formation of more ES,"},{"Start":"02:42.470 ","End":"02:45.515","Text":"enzyme substrate complex as substrate increases."},{"Start":"02:45.515 ","End":"02:53.225","Text":"Reminding you here, what we see is that the higher the concentration of substrate,"},{"Start":"02:53.225 ","End":"02:59.425","Text":"the more this will push forward to the enzyme substrate complex."},{"Start":"02:59.425 ","End":"03:02.180","Text":"The maximum initial rate, Vmax,"},{"Start":"03:02.180 ","End":"03:07.240","Text":"is observed when the enzyme is present as the ES complex."},{"Start":"03:07.240 ","End":"03:10.310","Text":"What this means is the maximum initial rate"},{"Start":"03:10.310 ","End":"03:14.810","Text":"Vmax of the catalyzed reaction is observed when"},{"Start":"03:14.810 ","End":"03:18.980","Text":"virtually all the enzyme is present as"},{"Start":"03:18.980 ","End":"03:24.050","Text":"the ES complex and free enzyme is vanishingly small."},{"Start":"03:24.050 ","End":"03:29.090","Text":"Under these conditions, the enzyme is saturated with its substrate so that"},{"Start":"03:29.090 ","End":"03:34.955","Text":"further increases in substrate concentration have no effect on the rate anymore."},{"Start":"03:34.955 ","End":"03:37.445","Text":"It\u0027s basically a plateau."},{"Start":"03:37.445 ","End":"03:42.305","Text":"This condition exists when substrate concentration is sufficiently high that essentially"},{"Start":"03:42.305 ","End":"03:47.230","Text":"all the free enzyme has been converted to ES form."},{"Start":"03:47.230 ","End":"03:53.450","Text":"After the ES complex breaks down to yield the product P,"},{"Start":"03:53.450 ","End":"03:58.520","Text":"the enzyme is free to catalyze reaction of another molecule of substrate, it can recycle."},{"Start":"03:58.520 ","End":"04:01.550","Text":"The saturation effect is a distinguishing characteristic of"},{"Start":"04:01.550 ","End":"04:05.570","Text":"enzymatic catalysts and is responsible for the plateau."},{"Start":"04:05.570 ","End":"04:08.435","Text":"Illustrated on this figure, again,"},{"Start":"04:08.435 ","End":"04:10.730","Text":"you have the idea that there\u0027s"},{"Start":"04:10.730 ","End":"04:17.065","Text":"so much substrate concentration that the enzyme is saturated with substrate."},{"Start":"04:17.065 ","End":"04:20.420","Text":"Then you have this plateau that adding more substrate doesn\u0027t"},{"Start":"04:20.420 ","End":"04:25.010","Text":"result in faster rates of the reaction."},{"Start":"04:25.010 ","End":"04:28.610","Text":"Therefore, you may see a recycling"},{"Start":"04:28.610 ","End":"04:33.020","Text":"of enzyme but still there\u0027s so much substrate that the rate"},{"Start":"04:33.020 ","End":"04:36.920","Text":"of enzyme-catalyzed reaction is the same"},{"Start":"04:36.920 ","End":"04:42.185","Text":"because 10 enzymes can only catalyze 10 reactions."},{"Start":"04:42.185 ","End":"04:46.955","Text":"Even if one completes the reaction and there\u0027s still so much substrate waiting for it,"},{"Start":"04:46.955 ","End":"04:51.560","Text":"it will then create another reaction, catalyze another reaction."},{"Start":"04:51.560 ","End":"04:55.550","Text":"But the rate will somewhat remain constant because it\u0027s constantly going to be"},{"Start":"04:55.550 ","End":"04:59.945","Text":"these 10 enzymes are working as catalysts of these reactions."},{"Start":"04:59.945 ","End":"05:04.670","Text":"Now when the enzyme is first mixed with a large excess of substrate,"},{"Start":"05:04.670 ","End":"05:11.810","Text":"there is an initial period the pre-steady state,"},{"Start":"05:11.810 ","End":"05:17.660","Text":"during which the concentration of ES enzyme substrate builds up."},{"Start":"05:17.660 ","End":"05:25.190","Text":"This period is usually too short to be easily observed, lasting just microseconds."},{"Start":"05:25.190 ","End":"05:30.079","Text":"The reaction quickly achieves a steady state in which ES concentration,"},{"Start":"05:30.079 ","End":"05:33.200","Text":"enzyme substrate concentration, and the concentrations of"},{"Start":"05:33.200 ","End":"05:38.960","Text":"any other intermediates remains approximately constant over time."},{"Start":"05:38.960 ","End":"05:47.270","Text":"The concept of a steady-state was introduced by G. E. Briggs and Haldane in 1925."},{"Start":"05:47.270 ","End":"05:52.325","Text":"The measured initial velocity generally reflects the steady-state,"},{"Start":"05:52.325 ","End":"05:58.360","Text":"even though initial velocity is limited to the early part of the reaction and"},{"Start":"05:58.360 ","End":"06:04.580","Text":"analysis of these initial rates is referred to as steady-state kinetics."},{"Start":"06:04.580 ","End":"06:07.475","Text":"We talked about initial velocity,"},{"Start":"06:07.475 ","End":"06:13.780","Text":"that is the rate at which the reaction occurs as is catalyzed by"},{"Start":"06:13.780 ","End":"06:16.940","Text":"an enzyme with an enzyme-substrate complex"},{"Start":"06:16.940 ","End":"06:20.540","Text":"being a factor and substrate concentration playing a major role."},{"Start":"06:20.540 ","End":"06:22.160","Text":"But there is also"},{"Start":"06:22.160 ","End":"06:27.950","Text":"this initial period when the enzyme is first mixed with a large excess of substrate."},{"Start":"06:27.950 ","End":"06:33.890","Text":"This initial period, the pre-steady state is one in which the concentration"},{"Start":"06:33.890 ","End":"06:40.490","Text":"of enzyme substrate complex builds up and it is usually so short,"},{"Start":"06:40.490 ","End":"06:46.040","Text":"it\u0027s not easily observed because it\u0027s only microseconds because"},{"Start":"06:46.040 ","End":"06:48.710","Text":"very quickly the substrate and the enzymes"},{"Start":"06:48.710 ","End":"06:52.115","Text":"come together when there\u0027s a saturation of substrate."},{"Start":"06:52.115 ","End":"06:58.040","Text":"It quickly achieves a steady state in which enzyme substrate concentration,"},{"Start":"06:58.040 ","End":"07:02.165","Text":"the concentration of any other intermediates remains approximately constant."},{"Start":"07:02.165 ","End":"07:05.015","Text":"That is where the term steady-state comes from because it\u0027s"},{"Start":"07:05.015 ","End":"07:09.685","Text":"a steady-state of concentration, it\u0027s somewhat constant."},{"Start":"07:09.685 ","End":"07:13.985","Text":"The constant of a steady-state was introduced."},{"Start":"07:13.985 ","End":"07:19.115","Text":"This concept of the steady-state was introduced by Briggs and Haldane in 1925."},{"Start":"07:19.115 ","End":"07:21.875","Text":"Now the measured initial velocity,"},{"Start":"07:21.875 ","End":"07:26.900","Text":"the measured reaction rate generally reflects"},{"Start":"07:26.900 ","End":"07:28.835","Text":"the steady-state even though"},{"Start":"07:28.835 ","End":"07:32.990","Text":"initial velocity is limited to the early part of the reaction."},{"Start":"07:32.990 ","End":"07:39.500","Text":"Analysis of these initial rates is referred to as steady-state kinetics,"},{"Start":"07:39.500 ","End":"07:45.230","Text":"because kinetics is the study of the rates of this steady-state."},{"Start":"07:45.230 ","End":"07:48.995","Text":"With this, we completed the introduction to enzyme kinetics,"},{"Start":"07:48.995 ","End":"07:51.455","Text":"both parts within the chapter of enzymes,"},{"Start":"07:51.455 ","End":"07:56.680","Text":"and we should have an understanding of kinetics of enzyme-catalyzed reactions,"},{"Start":"07:56.680 ","End":"07:58.985","Text":"be able to describe the theory of enzyme action,"},{"Start":"07:58.985 ","End":"08:01.739","Text":"and define steady-state kinetics."}],"ID":30144},{"Watched":false,"Name":"Exercise 1","Duration":"4m 37s","ChapterTopicVideoID":28594,"CourseChapterTopicPlaylistID":286644,"HasSubtitles":true,"ThumbnailPath":null,"UploadDate":null,"DurationForVideoObject":null,"Description":null,"MetaTitle":null,"MetaDescription":null,"Canonical":null,"VideoComments":[],"Subtitles":[{"Start":"00:00.000 ","End":"00:04.530","Text":"We\u0027re going to dive into some exercise with an intro to enzyme kinetics."},{"Start":"00:04.530 ","End":"00:09.345","Text":"What is the initial rate or initial velocity of a reaction,"},{"Start":"00:09.345 ","End":"00:11.550","Text":"and what is maximum velocity?"},{"Start":"00:11.550 ","End":"00:14.250","Text":"These are terms that we introduced in the lesson,"},{"Start":"00:14.250 ","End":"00:17.505","Text":"and these we basically said are synonymous."},{"Start":"00:17.505 ","End":"00:26.025","Text":"Initial rate, or initial velocity of reaction is designated V_0."},{"Start":"00:26.025 ","End":"00:31.380","Text":"Initial velocity varies by different substrate concentrations"},{"Start":"00:31.380 ","End":"00:37.040","Text":"even if and when the enzyme concentration is held constant as can be seen in the figure."},{"Start":"00:37.040 ","End":"00:41.180","Text":"Here you can consider that the enzyme is constant and what we\u0027re seeing"},{"Start":"00:41.180 ","End":"00:46.445","Text":"x-axis is that the substrate concentration [S],"},{"Start":"00:46.445 ","End":"00:49.910","Text":"millimolars increases as we move along"},{"Start":"00:49.910 ","End":"00:53.450","Text":"the x-axis from left to right and initial velocity also"},{"Start":"00:53.450 ","End":"01:00.320","Text":"known as initial rate which is V_0 is on the y-axis and is increasing as we go up."},{"Start":"01:00.320 ","End":"01:02.015","Text":"This is a measure,"},{"Start":"01:02.015 ","End":"01:06.780","Text":"so velocity is a measure change over time."},{"Start":"01:06.780 ","End":"01:09.660","Text":"It\u0027s the change of concentration here over"},{"Start":"01:09.660 ","End":"01:13.865","Text":"time and the units are micro molars per minute."},{"Start":"01:13.865 ","End":"01:17.960","Text":"As you see even if enzyme concentration is"},{"Start":"01:17.960 ","End":"01:23.315","Text":"held constant as the substrate concentration is changing,"},{"Start":"01:23.315 ","End":"01:27.290","Text":"we see a change in the initial velocity."},{"Start":"01:27.290 ","End":"01:31.350","Text":"At relatively low concentrations of substrate,"},{"Start":"01:31.350 ","End":"01:37.415","Text":"initial rate increases almost linearly with an increase in substrate concentration."},{"Start":"01:37.415 ","End":"01:39.005","Text":"What am I saying here?"},{"Start":"01:39.005 ","End":"01:41.030","Text":"You have low concentration of substrate,"},{"Start":"01:41.030 ","End":"01:43.285","Text":"this is the lower side here."},{"Start":"01:43.285 ","End":"01:47.135","Text":"Let\u0027s consider this lower concentration of substrate."},{"Start":"01:47.135 ","End":"01:52.220","Text":"You see that the initial velocity with the initial rate increases"},{"Start":"01:52.220 ","End":"01:57.920","Text":"almost linearly with the increase in S. You can consider looking at this,"},{"Start":"01:57.920 ","End":"02:00.890","Text":"and thinking that there is a line here that"},{"Start":"02:00.890 ","End":"02:04.174","Text":"was a very straight line as you could see but basically,"},{"Start":"02:04.174 ","End":"02:08.120","Text":"you could say almost that it\u0027s a linear increase."},{"Start":"02:08.120 ","End":"02:10.430","Text":"This is almost like saying,"},{"Start":"02:10.430 ","End":"02:12.819","Text":"if I draw here a flat line,"},{"Start":"02:12.819 ","End":"02:16.470","Text":"it\u0027s almost like a linear increase."},{"Start":"02:16.470 ","End":"02:22.010","Text":"Now at higher substrate concentrations you see that the initial velocity,"},{"Start":"02:22.010 ","End":"02:27.110","Text":"the initial rate, increases by smaller and smaller amounts in"},{"Start":"02:27.110 ","End":"02:28.880","Text":"response to increase in"},{"Start":"02:28.880 ","End":"02:32.525","Text":"substrate concentration and that\u0027s if we\u0027re looking at the higher here."},{"Start":"02:32.525 ","End":"02:37.270","Text":"This region here you\u0027re seeing that even though substrate concentration is"},{"Start":"02:37.270 ","End":"02:41.994","Text":"increasing there isn\u0027t much of a change to the initial velocity."},{"Start":"02:41.994 ","End":"02:47.050","Text":"If we had to mark it and measure you\u0027d see,"},{"Start":"02:47.050 ","End":"02:55.780","Text":"this is here and then you go up too much of a larger point of substrate concentration."},{"Start":"02:55.780 ","End":"02:57.940","Text":"The changes are really small,"},{"Start":"02:57.940 ","End":"03:00.204","Text":"they\u0027re really close together."},{"Start":"03:00.204 ","End":"03:04.561","Text":"If we\u0027re looking at these higher substrate concentrations this region."},{"Start":"03:04.561 ","End":"03:08.260","Text":"Higher concentration of substrate we see that"},{"Start":"03:08.260 ","End":"03:09.970","Text":"the initial velocity increases by"},{"Start":"03:09.970 ","End":"03:12.520","Text":"smaller and smaller amounts in response to the increase in"},{"Start":"03:12.520 ","End":"03:16.090","Text":"substrate and what this means is if we look at this point"},{"Start":"03:16.090 ","End":"03:18.580","Text":"here of the substrate concentration"},{"Start":"03:18.580 ","End":"03:21.310","Text":"and the substrate concentration here and the substrate concentration here,"},{"Start":"03:21.310 ","End":"03:26.110","Text":"which may be more significant in changes when we look at"},{"Start":"03:26.110 ","End":"03:32.620","Text":"this with regard to initial velocity and we try to mark it on the y-axis."},{"Start":"03:32.620 ","End":"03:34.270","Text":"Let\u0027s say it\u0027s here."},{"Start":"03:34.270 ","End":"03:38.135","Text":"Then we move up to this right here,"},{"Start":"03:38.135 ","End":"03:42.010","Text":"and we try to mark this on the y-axis."},{"Start":"03:42.010 ","End":"03:44.920","Text":"Let\u0027s see if I could do this."},{"Start":"03:44.920 ","End":"03:52.295","Text":"This right here which is even higher again trying to mark this on the y-axis,"},{"Start":"03:52.295 ","End":"03:56.109","Text":"it almost corresponds to the same initial velocity."},{"Start":"03:56.109 ","End":"04:00.760","Text":"Now finally a point is reached beyond where"},{"Start":"04:00.760 ","End":"04:06.685","Text":"increases in velocity are vanishingly small as substrate increases."},{"Start":"04:06.685 ","End":"04:11.375","Text":"This plateau that we see here it\u0027s almost flat."},{"Start":"04:11.375 ","End":"04:14.660","Text":"This plateau like velocity region is close to"},{"Start":"04:14.660 ","End":"04:19.355","Text":"the maximum velocity that is designated Vmax."},{"Start":"04:19.355 ","End":"04:25.395","Text":"This is what we see here, it\u0027s reaching close to this Vmax line."},{"Start":"04:25.395 ","End":"04:27.320","Text":"With that, we\u0027ve covered initial rate,"},{"Start":"04:27.320 ","End":"04:30.635","Text":"or initial velocity which we designate V_0,"},{"Start":"04:30.635 ","End":"04:36.750","Text":"and we talked about what maximum velocity is, Vmax."}],"ID":30145},{"Watched":false,"Name":"Exercise 2 Part 1","Duration":"5m 57s","ChapterTopicVideoID":28595,"CourseChapterTopicPlaylistID":286644,"HasSubtitles":true,"ThumbnailPath":null,"UploadDate":null,"DurationForVideoObject":null,"Description":null,"MetaTitle":null,"MetaDescription":null,"Canonical":null,"VideoComments":[],"Subtitles":[{"Start":"00:00.410 ","End":"00:04.844","Text":"We have another exercise with an intro to enzyme kinetics."},{"Start":"00:04.844 ","End":"00:09.705","Text":"Describe the theory of enzyme action partially by filling in the blanks."},{"Start":"00:09.705 ","End":"00:13.035","Text":"This theory was an expansion of known ideas by Leonor Michaelis,"},{"Start":"00:13.035 ","End":"00:15.270","Text":"and Maud Menten in 1913."},{"Start":"00:15.270 ","End":"00:17.565","Text":"Remember, Michaelis-Menten equation."},{"Start":"00:17.565 ","End":"00:24.720","Text":"The enzyme first combines blank with it\u0027s blank to form an blank."},{"Start":"00:24.720 ","End":"00:28.920","Text":"An gives you a clue that it\u0027s going to be a vowel."},{"Start":"00:28.920 ","End":"00:32.780","Text":"Then you have this equation right here."},{"Start":"00:32.780 ","End":"00:34.460","Text":"Enzyme plus substrate,"},{"Start":"00:34.460 ","End":"00:37.790","Text":"reversible reaction to enzyme-substrate complex."},{"Start":"00:37.790 ","End":"00:40.490","Text":"We\u0027re starting to describe the theory, events, and action."},{"Start":"00:40.490 ","End":"00:42.650","Text":"Talking about this theory that was an expansion of"},{"Start":"00:42.650 ","End":"00:45.860","Text":"known ideas by Michaelis and Menten 13,"},{"Start":"00:45.860 ","End":"00:49.820","Text":"and it talks about enzyme which combines with something and"},{"Start":"00:49.820 ","End":"00:54.840","Text":"something to form something with this equation following."},{"Start":"00:54.840 ","End":"00:57.540","Text":"Maybe talking about these things."},{"Start":"00:57.540 ","End":"00:59.340","Text":"Let\u0027s just move on and read this,"},{"Start":"00:59.340 ","End":"01:02.585","Text":"the rest, and then we\u0027ll go back and fill in the blanks."},{"Start":"01:02.585 ","End":"01:10.160","Text":"The enzyme-substrate complex then breaks down in a slower second step to yield blank."},{"Start":"01:10.160 ","End":"01:12.705","Text":"We have the enzyme-substrate complex,"},{"Start":"01:12.705 ","End":"01:14.040","Text":"and it yields,"},{"Start":"01:14.040 ","End":"01:17.040","Text":"in a reversible reaction, enzyme end-products."},{"Start":"01:17.040 ","End":"01:21.215","Text":"Free enzyme, and the resulting product from the reaction."},{"Start":"01:21.215 ","End":"01:25.785","Text":"Maybe this is hinting on to what will follow length with."},{"Start":"01:25.785 ","End":"01:27.950","Text":"Because the blank,"},{"Start":"01:27.950 ","End":"01:31.715","Text":"second reaction, blank the rate of the overall reaction,"},{"Start":"01:31.715 ","End":"01:35.840","Text":"the overall rate is proportional to the something of"},{"Start":"01:35.840 ","End":"01:41.285","Text":"the species that reacts in a second step that is enzyme-substrate complex."},{"Start":"01:41.285 ","End":"01:46.085","Text":"Let\u0027s go back and start with the first portion that we talked"},{"Start":"01:46.085 ","End":"01:51.310","Text":"about referring to the ideas expanded by Michaelis and Menten."},{"Start":"01:51.310 ","End":"01:59.045","Text":"The enzyme first combines with its something to form an something."},{"Start":"01:59.045 ","End":"02:02.015","Text":"An, we know this is a vowel."},{"Start":"02:02.015 ","End":"02:05.570","Text":"The enzyme first combines,"},{"Start":"02:05.570 ","End":"02:08.645","Text":"not sure yet what we\u0027re talking about,"},{"Start":"02:08.645 ","End":"02:09.830","Text":"but to form what?"},{"Start":"02:09.830 ","End":"02:11.315","Text":"Well, if we look at this equation,"},{"Start":"02:11.315 ","End":"02:14.095","Text":"I would say, this probably goes here."},{"Start":"02:14.095 ","End":"02:16.850","Text":"We know this goes here."},{"Start":"02:16.850 ","End":"02:18.290","Text":"We mentioned the enzyme."},{"Start":"02:18.290 ","End":"02:19.520","Text":"Enzyme first combines."},{"Start":"02:19.520 ","End":"02:26.260","Text":"Something here, this is probably referring because this is the enzyme, so substrate."},{"Start":"02:26.260 ","End":"02:31.825","Text":"The enzyme first combines with substrate,"},{"Start":"02:31.825 ","End":"02:37.710","Text":"and this reversible reaction to form an enzyme-substrate complex."},{"Start":"02:37.710 ","End":"02:39.680","Text":"The enzyme first combines,"},{"Start":"02:39.680 ","End":"02:43.534","Text":"we want to say substrate somewhere combined substrate with its substrate. Who know?"},{"Start":"02:43.534 ","End":"02:45.815","Text":"Maybe the enzyme first combines,"},{"Start":"02:45.815 ","End":"02:47.840","Text":"and let\u0027s ignore this first blank,"},{"Start":"02:47.840 ","End":"02:52.430","Text":"with its, maybe this here is substrate."},{"Start":"02:52.430 ","End":"02:55.475","Text":"Then what can this mean over here?"},{"Start":"02:55.475 ","End":"02:59.360","Text":"The enzyme first combines maybe"},{"Start":"02:59.360 ","End":"03:05.615","Text":"reversibly with its substrate to form an enzyme-substrate complex."},{"Start":"03:05.615 ","End":"03:09.245","Text":"The enzyme first combines reversibly,"},{"Start":"03:09.245 ","End":"03:11.380","Text":"as seen by these arrows,"},{"Start":"03:11.380 ","End":"03:14.250","Text":"with its, let\u0027s now say,"},{"Start":"03:14.250 ","End":"03:20.520","Text":"substrate to form an enzyme-substrate complex."},{"Start":"03:20.520 ","End":"03:25.610","Text":"This clue, that\u0027s it. The enzyme-substrate complex"},{"Start":"03:25.610 ","End":"03:27.920","Text":"then breaks down in a slower second step,"},{"Start":"03:27.920 ","End":"03:32.115","Text":"this one is slower than the first step, to yield what?"},{"Start":"03:32.115 ","End":"03:35.915","Text":"Enzyme end-products, so free enzyme end-product,"},{"Start":"03:35.915 ","End":"03:41.165","Text":"the free enzyme and the reaction product, P. Next,"},{"Start":"03:41.165 ","End":"03:46.760","Text":"because the blank second reaction blank the rate of the overall reaction,"},{"Start":"03:46.760 ","End":"03:49.100","Text":"the overall rate is proportional to"},{"Start":"03:49.100 ","End":"03:51.770","Text":"the blank of the species that reacts on a second step,"},{"Start":"03:51.770 ","End":"03:53.450","Text":"that is the enzyme-substrate."},{"Start":"03:53.450 ","End":"03:59.360","Text":"We talked about a slower second step because maybe,"},{"Start":"03:59.360 ","End":"04:02.410","Text":"it means the slower second reaction,"},{"Start":"04:02.410 ","End":"04:09.005","Text":"it is the one that probably affects and limits the rate of the overall reaction."},{"Start":"04:09.005 ","End":"04:13.435","Text":"Again, this may be what comes here,"},{"Start":"04:13.435 ","End":"04:16.880","Text":"and that\u0027s what we mean because"},{"Start":"04:16.880 ","End":"04:21.800","Text":"the slower second reaction limits the rate of the overall reaction."},{"Start":"04:21.800 ","End":"04:23.945","Text":"The overall rate is proportional to"},{"Start":"04:23.945 ","End":"04:28.100","Text":"the what of the species that reacts in the second step?"},{"Start":"04:28.100 ","End":"04:30.580","Text":"That is the ES."},{"Start":"04:30.580 ","End":"04:33.840","Text":"Well, the concentration."},{"Start":"04:33.840 ","End":"04:38.840","Text":"What we know about the theory of enzyme action is that this theory"},{"Start":"04:38.840 ","End":"04:43.595","Text":"was an expansion of a known ideas by Leonor Michaelis and Maud Menten in 1913."},{"Start":"04:43.595 ","End":"04:46.010","Text":"The enzyme first combines reversibly,"},{"Start":"04:46.010 ","End":"04:49.270","Text":"as seen in this reversible reaction, with its substrate."},{"Start":"04:49.270 ","End":"04:53.930","Text":"It can combine with a substrate and it\u0027s reversible to form an enzyme-substrate complex"},{"Start":"04:53.930 ","End":"04:58.690","Text":"that can also break apart to become free enzyme and free substrate."},{"Start":"04:58.690 ","End":"05:04.399","Text":"The complex then breaks down any slower second reaction, this is relatively fast,"},{"Start":"05:04.399 ","End":"05:08.360","Text":"and this is a slow reaction where the enzyme-substrate complex breaks"},{"Start":"05:08.360 ","End":"05:12.680","Text":"down to free up the enzyme and the product of the reaction."},{"Start":"05:12.680 ","End":"05:15.465","Text":"Because the second reaction is slower,"},{"Start":"05:15.465 ","End":"05:18.740","Text":"it limits the rate of the overall reaction."},{"Start":"05:18.740 ","End":"05:27.799","Text":"I\u0027m skipping"},{"Start":"05:27.799 ","End":"05:30.440","Text":"the intermediate right here,"},{"Start":"05:30.440 ","End":"05:33.605","Text":"which would be the enzyme-substrate complex and the enzyme product complex."},{"Start":"05:33.605 ","End":"05:35.660","Text":"Anyway, it\u0027s proportional to"},{"Start":"05:35.660 ","End":"05:39.290","Text":"the concentration of the species that reacts in a second step,"},{"Start":"05:39.290 ","End":"05:42.375","Text":"that is ES, the enzyme-substrate complex."},{"Start":"05:42.375 ","End":"05:50.420","Text":"The concentration of this is proportional to the overall rate."},{"Start":"05:50.420 ","End":"05:56.550","Text":"Now, we will meet back to continue this exercise in its second part."}],"ID":30146},{"Watched":false,"Name":"Exercise 2 Part 2","Duration":"10m 58s","ChapterTopicVideoID":28596,"CourseChapterTopicPlaylistID":286644,"HasSubtitles":true,"ThumbnailPath":null,"UploadDate":null,"DurationForVideoObject":null,"Description":null,"MetaTitle":null,"MetaDescription":null,"Canonical":null,"VideoComments":[],"Subtitles":[{"Start":"00:00.000 ","End":"00:04.365","Text":"Let\u0027s continue testing our knowledge on the theory of enzyme action."},{"Start":"00:04.365 ","End":"00:06.170","Text":"Describe the theory of enzyme action,"},{"Start":"00:06.170 ","End":"00:07.770","Text":"partially by filling in the blanks."},{"Start":"00:07.770 ","End":"00:10.470","Text":"At any given instant in an enzyme catalyzed reaction,"},{"Start":"00:10.470 ","End":"00:13.980","Text":"the enzyme exists in a blank column, blank, blank."},{"Start":"00:13.980 ","End":"00:18.300","Text":"This refers to something that\u0027s talking about 2 things that are described here."},{"Start":"00:18.300 ","End":"00:20.100","Text":"At low substrate concentration,"},{"Start":"00:20.100 ","End":"00:26.235","Text":"most of the blank is in the uncombined form E. What does E stand for?"},{"Start":"00:26.235 ","End":"00:32.045","Text":"Enzyme. Here, the rate is blank to the substrate concentration."},{"Start":"00:32.045 ","End":"00:34.100","Text":"The equilibrium is pushed toward formation of"},{"Start":"00:34.100 ","End":"00:37.385","Text":"more blank as substrate concentration increases."},{"Start":"00:37.385 ","End":"00:39.920","Text":"When we have substrate concentration increasing,"},{"Start":"00:39.920 ","End":"00:44.345","Text":"equilibrium is pushed towards formation of more what?"},{"Start":"00:44.345 ","End":"00:46.475","Text":"This may be a hint as to going here."},{"Start":"00:46.475 ","End":"00:48.480","Text":"The maximum initial rate of"},{"Start":"00:48.480 ","End":"00:52.550","Text":"the catalyzed reaction V_max is observed when virtually all the enzyme"},{"Start":"00:52.550 ","End":"00:59.570","Text":"is present as blank and blank is vanishingly small."},{"Start":"00:59.570 ","End":"01:04.880","Text":"Under these conditions, the enzyme is blank with its substrate,"},{"Start":"01:04.880 ","End":"01:11.485","Text":"so that further blank in substrate concentration have no effect on blank."},{"Start":"01:11.485 ","End":"01:16.070","Text":"After the ES complex breaks down to yield the blank,"},{"Start":"01:16.070 ","End":"01:21.890","Text":"the enzyme is blank to catalyze reaction of another molecule of substrate."},{"Start":"01:21.890 ","End":"01:25.040","Text":"Let\u0027s go back up, and hopefully this triggered"},{"Start":"01:25.040 ","End":"01:29.875","Text":"a few different thoughts and memories with regard to things we\u0027ve covered."},{"Start":"01:29.875 ","End":"01:31.435","Text":"Let\u0027s start at the beginning."},{"Start":"01:31.435 ","End":"01:34.295","Text":"At any given instant in an enzyme catalyzed reaction,"},{"Start":"01:34.295 ","End":"01:36.830","Text":"the enzyme exists in blank,"},{"Start":"01:36.830 ","End":"01:39.070","Text":"corresponding to 2 things."},{"Start":"01:39.070 ","End":"01:41.240","Text":"An enzyme catalyzed reaction,"},{"Start":"01:41.240 ","End":"01:45.270","Text":"the enzyme can exist in what we talked about,"},{"Start":"01:45.640 ","End":"01:51.260","Text":"a form that is basically either combined in a complex or not."},{"Start":"01:51.260 ","End":"01:55.520","Text":"It exists in 2 forms."},{"Start":"01:55.520 ","End":"01:57.830","Text":"What are these forms?"},{"Start":"01:57.830 ","End":"02:04.685","Text":"Well, we have the one that is basically free and we have one that is in a complex."},{"Start":"02:04.685 ","End":"02:12.350","Text":"We have the free form E enzyme and the combined form ES, enzyme substrate complex."},{"Start":"02:12.350 ","End":"02:14.840","Text":"At low substrate concentration,"},{"Start":"02:14.840 ","End":"02:17.960","Text":"most of the blank is in"},{"Start":"02:17.960 ","End":"02:24.785","Text":"the uncombined form E. We just mentioned that the enzyme exists in 2 forms,"},{"Start":"02:24.785 ","End":"02:29.930","Text":"and one of them is this free form E. At low substrate concentration,"},{"Start":"02:29.930 ","End":"02:38.075","Text":"most of the enzyme exists in the form of the uncombined form E, so enzyme."},{"Start":"02:38.075 ","End":"02:44.885","Text":"Now here, the rate is what to the substrate concentration and it expands."},{"Start":"02:44.885 ","End":"02:50.750","Text":"The equilibrium is pushed toward formation of more something as substrate increases."},{"Start":"02:50.750 ","End":"02:53.210","Text":"We mentioned, we have this equation here,"},{"Start":"02:53.210 ","End":"02:54.760","Text":"again, this is a hint."},{"Start":"02:54.760 ","End":"02:57.375","Text":"This probably refers to the ES complex,"},{"Start":"02:57.375 ","End":"03:04.340","Text":"so the rate we talked previously about the very fast reversible step of this versus"},{"Start":"03:04.340 ","End":"03:08.270","Text":"the slowest step of ES complex breaking up"},{"Start":"03:08.270 ","End":"03:12.485","Text":"into free enzyme plus product reaction product."},{"Start":"03:12.485 ","End":"03:16.625","Text":"Then here you have the limiting step is"},{"Start":"03:16.625 ","End":"03:24.230","Text":"the second slower step and therefore the overall reaction rate is proportional to this,"},{"Start":"03:24.230 ","End":"03:30.395","Text":"where here we\u0027re talking about the rate is what to substrate concentration?"},{"Start":"03:30.395 ","End":"03:35.135","Text":"Well, proportional to substrate concentration because the higher this is,"},{"Start":"03:35.135 ","End":"03:39.320","Text":"the more of this direction going from"},{"Start":"03:39.320 ","End":"03:43.775","Text":"left to right and production of ES is pushed towards."},{"Start":"03:43.775 ","End":"03:46.500","Text":"Here the rate is proportional to substrate concentration,"},{"Start":"03:46.500 ","End":"03:48.380","Text":"the equilibrium is pushed toward formation of"},{"Start":"03:48.380 ","End":"03:54.005","Text":"more enzyme substrate complex as substrate increases."},{"Start":"03:54.005 ","End":"03:57.290","Text":"Now the maximum initial rate of a catalyzed reaction, V_max,"},{"Start":"03:57.290 ","End":"04:00.545","Text":"is observed when virtually all the enzyme is present as"},{"Start":"04:00.545 ","End":"04:05.175","Text":"what and what is vanishingly small?"},{"Start":"04:05.175 ","End":"04:07.340","Text":"Well, when we see V_max,"},{"Start":"04:07.340 ","End":"04:10.730","Text":"if you remember that curve that we went over in the lesson,"},{"Start":"04:10.730 ","End":"04:14.600","Text":"we see it as substrate concentration goes up,"},{"Start":"04:14.600 ","End":"04:20.425","Text":"and initial velocity increases as substrate concentration goes up."},{"Start":"04:20.425 ","End":"04:25.300","Text":"This means that here close to V_max, up here,"},{"Start":"04:25.300 ","End":"04:27.640","Text":"enzyme is completely saturated with substrate,"},{"Start":"04:27.640 ","End":"04:32.445","Text":"meaning that virtually all the enzyme is present as what?"},{"Start":"04:32.445 ","End":"04:34.890","Text":"An associated complex with the substrate,"},{"Start":"04:34.890 ","End":"04:39.115","Text":"so as the ES complex and what is vanishingly small?"},{"Start":"04:39.115 ","End":"04:41.425","Text":"Well, the uncombined form E,"},{"Start":"04:41.425 ","End":"04:43.795","Text":"the free form of the enzyme,"},{"Start":"04:43.795 ","End":"04:46.765","Text":"the enzyme concentration is vanishingly small."},{"Start":"04:46.765 ","End":"04:51.130","Text":"Under these conditions, the enzyme is blank with its substrate so that"},{"Start":"04:51.130 ","End":"04:55.690","Text":"further blank in substrate concentration have no effect on blank."},{"Start":"04:55.690 ","End":"04:59.020","Text":"Basically we just said all enzyme is for substrate,"},{"Start":"04:59.020 ","End":"05:05.420","Text":"it is initiated and the word we mentioned is saturated with its substrate"},{"Start":"05:05.420 ","End":"05:12.320","Text":"so that further in substrate concentration have no effect on what?"},{"Start":"05:12.320 ","End":"05:14.720","Text":"As substrate concentration increases,"},{"Start":"05:14.720 ","End":"05:20.315","Text":"further increases in substrate concentration have no effect on,"},{"Start":"05:20.315 ","End":"05:23.030","Text":"well, what did we talk about here?"},{"Start":"05:23.030 ","End":"05:26.615","Text":"We mentioned the proportionality to the rate,"},{"Start":"05:26.615 ","End":"05:29.855","Text":"so have no effect on rate."},{"Start":"05:29.855 ","End":"05:34.880","Text":"After the ES complex enzyme substrate complex breaks down to yield the,"},{"Start":"05:34.880 ","End":"05:36.860","Text":"we just mentioned, we wrote out,"},{"Start":"05:36.860 ","End":"05:39.305","Text":"what is this next step?"},{"Start":"05:39.305 ","End":"05:43.735","Text":"What is this lower step the E and P?"},{"Start":"05:43.735 ","End":"05:47.000","Text":"We get the E and P. After the ES complex breakdown to"},{"Start":"05:47.000 ","End":"05:49.670","Text":"yield the either free enzyme or product,"},{"Start":"05:49.670 ","End":"05:50.960","Text":"the enzyme is what?"},{"Start":"05:50.960 ","End":"05:52.685","Text":"Here\u0027s probably product,"},{"Start":"05:52.685 ","End":"05:56.375","Text":"while this is talking about the enzyme is free."},{"Start":"05:56.375 ","End":"06:01.010","Text":"Now it\u0027s uncombined enzyme to bind substrate"},{"Start":"06:01.010 ","End":"06:06.655","Text":"again and catalyze reaction of another molecule of substrate."},{"Start":"06:06.655 ","End":"06:11.225","Text":"We can say, after the ES complex breakdown to yield the product P,"},{"Start":"06:11.225 ","End":"06:15.545","Text":"the enzyme is free to catalyze reaction of another molecule of substrate."},{"Start":"06:15.545 ","End":"06:18.010","Text":"Let us go through what we just said."},{"Start":"06:18.010 ","End":"06:20.720","Text":"At any given instant in an enzyme catalyzed reaction,"},{"Start":"06:20.720 ","End":"06:22.070","Text":"the enzyme exists in 2 forms,"},{"Start":"06:22.070 ","End":"06:24.830","Text":"the free form E and the combined form ES."},{"Start":"06:24.830 ","End":"06:26.390","Text":"At low substrate concentration,"},{"Start":"06:26.390 ","End":"06:31.700","Text":"most of the enzyme is in the uncombined form E. Here the rate is proportional to"},{"Start":"06:31.700 ","End":"06:35.030","Text":"substrate concentration and the equilibrium is pushed toward"},{"Start":"06:35.030 ","End":"06:38.585","Text":"formation of more ES as substrate concentration increases."},{"Start":"06:38.585 ","End":"06:44.390","Text":"When this increases, you see more of this reaction."},{"Start":"06:44.390 ","End":"06:47.240","Text":"Now that maximum initial rate of"},{"Start":"06:47.240 ","End":"06:50.750","Text":"the catalyzed reaction V_max is observed when virtually all the enzyme is"},{"Start":"06:50.750 ","End":"06:56.865","Text":"present as the ES complex and enzyme concentration is vanishingly small free enzyme."},{"Start":"06:56.865 ","End":"06:59.750","Text":"Under these conditions, the enzyme is saturated with its substrate so"},{"Start":"06:59.750 ","End":"07:02.510","Text":"that further increases in substrate concentration have no effect on"},{"Start":"07:02.510 ","End":"07:05.660","Text":"rate because at this point it\u0027s in a rate"},{"Start":"07:05.660 ","End":"07:09.740","Text":"of the amount of enzyme that can catalyze reaction,"},{"Start":"07:09.740 ","End":"07:12.725","Text":"all the enzyme is catalyzing reaction"},{"Start":"07:12.725 ","End":"07:16.190","Text":"and as substrate transfer product and product release the enzyme,"},{"Start":"07:16.190 ","End":"07:21.455","Text":"then can bind another substrate and then that means the speed is somewhat the same."},{"Start":"07:21.455 ","End":"07:24.380","Text":"Now after the ES complex breaks down to yield the product P,"},{"Start":"07:24.380 ","End":"07:27.965","Text":"that enzyme is free to catalyze reaction of another molecule of substrate."},{"Start":"07:27.965 ","End":"07:33.340","Text":"This entire question talked about the theory of enzyme action,"},{"Start":"07:33.340 ","End":"07:36.665","Text":"and let\u0027s go back to the first part,"},{"Start":"07:36.665 ","End":"07:38.800","Text":"describe the theory of enzyme action."},{"Start":"07:38.800 ","End":"07:43.770","Text":"This theory was an expansion of known ideas by Leonor Michaelis and Maud Menten in 1913."},{"Start":"07:43.770 ","End":"07:47.960","Text":"The enzyme first combines reversibly with its substrate to"},{"Start":"07:47.960 ","End":"07:54.500","Text":"form an enzyme substrate complex in a relatively fast reversible step,"},{"Start":"07:54.500 ","End":"07:58.970","Text":"E plus S reversible ES fast."},{"Start":"07:58.970 ","End":"08:01.850","Text":"The complex then breaks down in"},{"Start":"08:01.850 ","End":"08:08.660","Text":"a slower second step to yield the free enzyme and the reaction product P as seen here."},{"Start":"08:08.660 ","End":"08:15.410","Text":"We have ES and the substrate reversible reaction to free enzyme and reaction product."},{"Start":"08:15.410 ","End":"08:21.005","Text":"Because the slower second reaction limits the rate of the overall reaction,"},{"Start":"08:21.005 ","End":"08:24.985","Text":"the overall rate of the reaction is proportional"},{"Start":"08:24.985 ","End":"08:29.485","Text":"to the concentration of the species that reacts in a second step,"},{"Start":"08:29.485 ","End":"08:33.100","Text":"that is enzyme substrate complex, as in here,"},{"Start":"08:33.100 ","End":"08:39.560","Text":"the whole reaction is affected with this intermediate complex."},{"Start":"08:39.560 ","End":"08:42.730","Text":"We have enzyme plus substrate resulting in enzyme plus product."},{"Start":"08:42.730 ","End":"08:47.560","Text":"This intermediate complex affects the overall rate of reaction."},{"Start":"08:47.560 ","End":"08:49.825","Text":"Go into the second portion."},{"Start":"08:49.825 ","End":"08:53.230","Text":"At any given instant in an enzyme catalyzed reaction,"},{"Start":"08:53.230 ","End":"08:55.015","Text":"the enzyme exists in 2 forms."},{"Start":"08:55.015 ","End":"09:00.710","Text":"The free form E, and that is the free or uncombined form E,"},{"Start":"09:00.710 ","End":"09:03.570","Text":"and the combined form ES."},{"Start":"09:03.570 ","End":"09:05.250","Text":"At low substrate concentrations,"},{"Start":"09:05.250 ","End":"09:08.540","Text":"most of the enzyme is in the uncombined form E."},{"Start":"09:08.540 ","End":"09:12.395","Text":"Here the rate is proportional to substrate concentration because the equilibrium"},{"Start":"09:12.395 ","End":"09:20.000","Text":"of the equation is pushed forward towards formation of more ES,"},{"Start":"09:20.000 ","End":"09:24.965","Text":"enzyme substrate complex as substrate concentration increases,"},{"Start":"09:24.965 ","End":"09:28.115","Text":"as seen in this equation."},{"Start":"09:28.115 ","End":"09:30.350","Text":"The more substrate you have,"},{"Start":"09:30.350 ","End":"09:36.130","Text":"the more this reaction will turn and form ES."},{"Start":"09:36.130 ","End":"09:38.840","Text":"Now the maximum initial rate of the catalyzed reaction V_max"},{"Start":"09:38.840 ","End":"09:41.390","Text":"is observed when virtually all the enzyme is"},{"Start":"09:41.390 ","End":"09:46.895","Text":"present as the ES complex and concentration of enzyme is vanishingly small."},{"Start":"09:46.895 ","End":"09:50.180","Text":"Under these conditions, the enzyme is saturated with its substrate,"},{"Start":"09:50.180 ","End":"09:54.620","Text":"so that further increases in substrate concentration have no effect on rate."},{"Start":"09:54.620 ","End":"09:58.400","Text":"This condition exists when substrate concentration is sufficiently high that essentially"},{"Start":"09:58.400 ","End":"10:02.840","Text":"all the free enzyme has been converted to the ES form."},{"Start":"10:02.840 ","End":"10:07.055","Text":"Now after the ES complex breaks down to yield the product P,"},{"Start":"10:07.055 ","End":"10:11.015","Text":"the enzyme is free to catalyze reaction of another molecule of substrate."},{"Start":"10:11.015 ","End":"10:14.840","Text":"The saturating effect is a distinguishing characteristic of enzymatic catalysts"},{"Start":"10:14.840 ","End":"10:16.610","Text":"and is responsible for the plateau"},{"Start":"10:16.610 ","End":"10:19.065","Text":"observed in the figure that we introduced in the lesson,"},{"Start":"10:19.065 ","End":"10:27.335","Text":"where you have the enzyme reaction rate reaching this plateau that nears the V_max."},{"Start":"10:27.335 ","End":"10:32.030","Text":"Again, if we have the y-axis is initial rate"},{"Start":"10:32.030 ","End":"10:36.800","Text":"or initial velocity and the x-axis is substrate concentration."},{"Start":"10:36.800 ","End":"10:43.250","Text":"The idea is that when you have high amounts of substrate where the enzyme is saturated,"},{"Start":"10:43.250 ","End":"10:50.700","Text":"the saturation effect, then you see this plateau reaching the V_max."},{"Start":"10:50.700 ","End":"10:57.210","Text":"This all is also known as saturation kinetics."}],"ID":30147},{"Watched":false,"Name":"Exercise 3","Duration":"2m 33s","ChapterTopicVideoID":28597,"CourseChapterTopicPlaylistID":286644,"HasSubtitles":true,"ThumbnailPath":null,"UploadDate":null,"DurationForVideoObject":null,"Description":null,"MetaTitle":null,"MetaDescription":null,"Canonical":null,"VideoComments":[],"Subtitles":[{"Start":"00:00.000 ","End":"00:04.110","Text":"Welcome to another exercise within intro to enzyme kinetics."},{"Start":"00:04.110 ","End":"00:09.255","Text":"Define and explain steady-state kinetics and what the pre-steady state is."},{"Start":"00:09.255 ","End":"00:13.185","Text":"When the enzyme is first mixed with a large excess of substrate,"},{"Start":"00:13.185 ","End":"00:15.120","Text":"there is an initial period,"},{"Start":"00:15.120 ","End":"00:18.795","Text":"the pre-steady state during which the concentration of"},{"Start":"00:18.795 ","End":"00:23.505","Text":"enzyme substrate complex ES builds up."},{"Start":"00:23.505 ","End":"00:31.110","Text":"This period is usually too short to be easily observed, lasting just microseconds."},{"Start":"00:31.110 ","End":"00:36.725","Text":"The reaction quickly achieves a steady state in which the ES concentration,"},{"Start":"00:36.725 ","End":"00:38.990","Text":"the enzyme substrate complex,"},{"Start":"00:38.990 ","End":"00:42.140","Text":"and the concentration of any other intermediates of"},{"Start":"00:42.140 ","End":"00:46.985","Text":"the reaction remains approximately constant over time."},{"Start":"00:46.985 ","End":"00:50.360","Text":"Basically, what we\u0027re saying here is when the enzyme is first"},{"Start":"00:50.360 ","End":"00:53.405","Text":"mixed with a large excess of substrate,"},{"Start":"00:53.405 ","End":"00:59.000","Text":"the concentration of substrate is much greater than the enzyme concentration."},{"Start":"00:59.000 ","End":"01:01.340","Text":"Then the enzyme and substrate bond,"},{"Start":"01:01.340 ","End":"01:06.105","Text":"there\u0027s enough substrate to bind and saturate the enzyme"},{"Start":"01:06.105 ","End":"01:11.360","Text":"and it just happens in a very quick period of time where substrate and enzyme,"},{"Start":"01:11.360 ","End":"01:13.250","Text":"because they have an affinity of each other,"},{"Start":"01:13.250 ","End":"01:16.040","Text":"and there\u0027s so much substrate that all enzymes are"},{"Start":"01:16.040 ","End":"01:19.145","Text":"surrounded by enough substrate that they can bind right away."},{"Start":"01:19.145 ","End":"01:22.745","Text":"Therefore, this pre-steady state is when"},{"Start":"01:22.745 ","End":"01:27.350","Text":"the enzyme and substrate bind each other and the concentration of ES builds up."},{"Start":"01:27.350 ","End":"01:30.200","Text":"It\u0027s the pre-steady state because it happens so"},{"Start":"01:30.200 ","End":"01:33.395","Text":"fast that it\u0027s microseconds it\u0027s hard to observe."},{"Start":"01:33.395 ","End":"01:38.989","Text":"Then it quickly achieves a steady state in which the ES concentration,"},{"Start":"01:38.989 ","End":"01:42.920","Text":"the enzyme substrate concentration remains approximately constant because at"},{"Start":"01:42.920 ","End":"01:48.715","Text":"that point it\u0027s when all enzyme basically is bound to substrate."},{"Start":"01:48.715 ","End":"01:51.760","Text":"Even though enzyme catalyzed the reaction,"},{"Start":"01:51.760 ","End":"01:54.230","Text":"substrate is then released as product."},{"Start":"01:54.230 ","End":"01:57.950","Text":"The enzyme is recycled because it essentially"},{"Start":"01:57.950 ","End":"02:01.820","Text":"stays the same and can bind another substrate,"},{"Start":"02:01.820 ","End":"02:06.095","Text":"and therefore this remains approximately constant."},{"Start":"02:06.095 ","End":"02:14.900","Text":"Now, the concept of steady state was introduced by G. E. Briggs and Haldane in 1925."},{"Start":"02:14.900 ","End":"02:19.295","Text":"The measured initial velocity reflects the steady state."},{"Start":"02:19.295 ","End":"02:23.570","Text":"Even though initial velocity is limited to the early part of the reaction and"},{"Start":"02:23.570 ","End":"02:28.115","Text":"analysis of these initial rates is referred to as steady-state kinetics,"},{"Start":"02:28.115 ","End":"02:32.670","Text":"is the study of the kinetics of the steady state."}],"ID":30148},{"Watched":false,"Name":"Michaelis Menten Equation Part 1","Duration":"9m 10s","ChapterTopicVideoID":28598,"CourseChapterTopicPlaylistID":286644,"HasSubtitles":true,"ThumbnailPath":null,"UploadDate":null,"DurationForVideoObject":null,"Description":null,"MetaTitle":null,"MetaDescription":null,"Canonical":null,"VideoComments":[],"Subtitles":[{"Start":"00:00.000 ","End":"00:02.115","Text":"Hi, welcome back. We were within enzymes."},{"Start":"00:02.115 ","End":"00:06.675","Text":"We are going to talk about the Michaelis-Menten equation."},{"Start":"00:06.675 ","End":"00:07.980","Text":"By the end of this section,"},{"Start":"00:07.980 ","End":"00:10.635","Text":"you\u0027ll be able to describe the Michaelis-Menten equation,"},{"Start":"00:10.635 ","End":"00:12.765","Text":"explain a steady-state assumption,"},{"Start":"00:12.765 ","End":"00:14.940","Text":"and understand the terms initial velocity,"},{"Start":"00:14.940 ","End":"00:17.535","Text":"maximum velocity, and Michaelis constant."},{"Start":"00:17.535 ","End":"00:19.560","Text":"Considering there\u0027s a lot of information,"},{"Start":"00:19.560 ","End":"00:22.320","Text":"we\u0027ll split this and we\u0027re going to start with Part 1,"},{"Start":"00:22.320 ","End":"00:24.870","Text":"where we\u0027ll be focusing aside from talking about"},{"Start":"00:24.870 ","End":"00:28.910","Text":"the Michaelis-Menten equation and explain a steady-state assumption."},{"Start":"00:28.910 ","End":"00:32.880","Text":"We will understand the derivation of the Michaelis-Menten equation."},{"Start":"00:32.880 ","End":"00:36.270","Text":"The relationship between substrate concentration and reaction rate"},{"Start":"00:36.270 ","End":"00:40.350","Text":"can be expressed quantitatively by the Michaelis-Menten equation."},{"Start":"00:40.350 ","End":"00:46.685","Text":"The curve expressing the relationship between concentration substrate, and reactionary,"},{"Start":"00:46.685 ","End":"00:50.855","Text":"as illustrated in the figure we introduced in previous lesson,"},{"Start":"00:50.855 ","End":"00:54.720","Text":"has the same general shape for most enzymes."},{"Start":"00:54.720 ","End":"00:57.305","Text":"It approaches a rectangular hyperbola,"},{"Start":"00:57.305 ","End":"01:03.114","Text":"which can be expressed algebraically by the Michaelis-Menten equation."},{"Start":"01:03.114 ","End":"01:06.200","Text":"Michaelis-Menten, 2 scientists derive"},{"Start":"01:06.200 ","End":"01:09.560","Text":"this equation starting from the basic hypothesis that"},{"Start":"01:09.560 ","End":"01:13.700","Text":"the rate-limiting step in enzymatic reactions is the breakdown"},{"Start":"01:13.700 ","End":"01:19.000","Text":"of the enzyme substrate complex to product and free enzyme."},{"Start":"01:19.000 ","End":"01:25.100","Text":"The equation is initial rate or reaction rate,"},{"Start":"01:25.100 ","End":"01:32.750","Text":"initial velocity equals V_max times the substrate concentration over K_m,"},{"Start":"01:32.750 ","End":"01:38.700","Text":"which is the Michaelis constant, plus substrate concentration,"},{"Start":"01:38.700 ","End":"01:44.505","Text":"so that important terms are substrate concentration,"},{"Start":"01:44.505 ","End":"01:52.590","Text":"V_0, which is initial velocity, or reaction rate."},{"Start":"01:52.840 ","End":"02:00.950","Text":"V_max which is maximum velocity or maximum reaction rate,"},{"Start":"02:00.950 ","End":"02:06.635","Text":"and a constant called the Michaelis constant."},{"Start":"02:06.635 ","End":"02:10.130","Text":"All these terms are readily measured experimentally."},{"Start":"02:10.130 ","End":"02:13.775","Text":"Here, we develop the basic logic and the algebraic steps"},{"Start":"02:13.775 ","End":"02:17.825","Text":"in a modern derivation of a Michaelis-Menten equation,"},{"Start":"02:17.825 ","End":"02:20.750","Text":"which includes the steady-state assumption"},{"Start":"02:20.750 ","End":"02:24.425","Text":"introduced by Briggs and Haldane mentioned in the previous lesson."},{"Start":"02:24.425 ","End":"02:28.760","Text":"The derivation starts with the 2 basic steps of a formation"},{"Start":"02:28.760 ","End":"02:33.080","Text":"and break down of enzyme substrate complexes as"},{"Start":"02:33.080 ","End":"02:37.040","Text":"introduced in these formulas in the previous lesson where you see"},{"Start":"02:37.040 ","End":"02:41.870","Text":"enzyme plus substrate reversibly forming the enzyme-substrate complex."},{"Start":"02:41.870 ","End":"02:45.190","Text":"This is considered to be a fast reaction,"},{"Start":"02:45.190 ","End":"02:49.100","Text":"while the enzyme substrate complex then"},{"Start":"02:49.100 ","End":"02:54.335","Text":"results in the release of a product and free enzyme,"},{"Start":"02:54.335 ","End":"02:59.070","Text":"and this is considered to be a slower reaction."},{"Start":"02:59.360 ","End":"03:02.465","Text":"Early in the reaction,"},{"Start":"03:02.465 ","End":"03:08.750","Text":"the concentration of the product P is negligible because there isn\u0027t product and we make"},{"Start":"03:08.750 ","End":"03:15.545","Text":"the simplifying assumption that the reverse reaction p to substrate,"},{"Start":"03:15.545 ","End":"03:19.775","Text":"which is described by k_2,"},{"Start":"03:19.775 ","End":"03:22.295","Text":"but the reverse of it,"},{"Start":"03:22.295 ","End":"03:27.600","Text":"so this way can be ignored."},{"Start":"03:27.600 ","End":"03:31.595","Text":"Because we don\u0027t really have product yet."},{"Start":"03:31.595 ","End":"03:33.320","Text":"This assumption is not critical,"},{"Start":"03:33.320 ","End":"03:38.930","Text":"but it simplifies our task in the development of this algebraic concept."},{"Start":"03:38.930 ","End":"03:45.890","Text":"The overall reaction then reduces to this reaction right here,"},{"Start":"03:45.890 ","End":"03:50.225","Text":"where we have E enzyme plus substrate,"},{"Start":"03:50.225 ","End":"03:56.735","Text":"going to enzyme substrate complex and then going to enzyme plus product."},{"Start":"03:56.735 ","End":"03:59.960","Text":"Now, reaction rate is determined by the breakdown of"},{"Start":"03:59.960 ","End":"04:03.080","Text":"the enzyme substrate to form product,"},{"Start":"04:03.080 ","End":"04:06.454","Text":"which is determined by this equation."},{"Start":"04:06.454 ","End":"04:11.270","Text":"You have the reaction rate equals k_2,"},{"Start":"04:11.270 ","End":"04:13.850","Text":"which is this right here,"},{"Start":"04:13.850 ","End":"04:17.390","Text":"times the enzyme substrate concentration."},{"Start":"04:17.390 ","End":"04:23.255","Text":"Because enzyme substrate concentration is not easily measured experimentally,"},{"Start":"04:23.255 ","End":"04:26.690","Text":"we must begin by finding an alternative expression for this term."},{"Start":"04:26.690 ","End":"04:33.755","Text":"First we introduce the term E_t representing the total enzyme concentration,"},{"Start":"04:33.755 ","End":"04:37.325","Text":"the sum of free and substrate bound enzyme,"},{"Start":"04:37.325 ","End":"04:45.780","Text":"total enzyme concentration, the sum of free and substrate bound enzyme."},{"Start":"04:45.820 ","End":"04:48.930","Text":"This is E_t."},{"Start":"04:49.520 ","End":"04:57.830","Text":"Now, free or unbound enzyme can be represented by E_t to ES."},{"Start":"04:57.830 ","End":"05:01.330","Text":"Also because substrate concentration is ordinarily"},{"Start":"05:01.330 ","End":"05:04.975","Text":"far greater than the total concentration of enzyme,"},{"Start":"05:04.975 ","End":"05:09.670","Text":"the amount of substrate bound by the enzyme at any given time is"},{"Start":"05:09.670 ","End":"05:14.620","Text":"negligible compared with the total concentration of substrate."},{"Start":"05:14.620 ","End":"05:20.455","Text":"Basically, the idea is that these are related."},{"Start":"05:20.455 ","End":"05:22.430","Text":"With these conditions in mind,"},{"Start":"05:22.430 ","End":"05:25.600","Text":"the following steps lead us to an expression for"},{"Start":"05:25.600 ","End":"05:29.020","Text":"reactionary in terms of easily measurable parameters."},{"Start":"05:29.020 ","End":"05:33.110","Text":"We may not have to remember all the steps or understand all of them."},{"Start":"05:33.110 ","End":"05:37.910","Text":"But I\u0027m going to go over them and let\u0027s try our best to grasp the ideas."},{"Start":"05:37.910 ","End":"05:41.360","Text":"Step 1, the rates of formation and break"},{"Start":"05:41.360 ","End":"05:44.960","Text":"down of enzyme substrate are determined by the steps governed by"},{"Start":"05:44.960 ","End":"05:48.470","Text":"the rate constant k_1 formation and k negative 1 plus"},{"Start":"05:48.470 ","End":"05:52.380","Text":"k_2 breakdown according to the expressions below."},{"Start":"05:52.380 ","End":"05:55.610","Text":"Rate of enzyme substrate information is k_1 over"},{"Start":"05:55.610 ","End":"06:00.320","Text":"total enzyme concentration minus enzyme substrate concentration,"},{"Start":"06:00.320 ","End":"06:02.510","Text":"and this time substrate concentration,"},{"Start":"06:02.510 ","End":"06:06.320","Text":"the rate of the enzyme substrate breakdown is k negative 1,"},{"Start":"06:06.320 ","End":"06:08.705","Text":"where you have enzyme substrate concentration plus"},{"Start":"06:08.705 ","End":"06:12.730","Text":"k_2 times the concentration of enzyme substrate."},{"Start":"06:12.730 ","End":"06:16.980","Text":"Just reminding you, k_1 refers to this right here,"},{"Start":"06:16.980 ","End":"06:19.890","Text":"k negative 1 is the reverse direction."},{"Start":"06:19.890 ","End":"06:27.110","Text":"Rate of ES formation is this direction of ES breakdown is the other direction."},{"Start":"06:27.110 ","End":"06:30.890","Text":"You have k_1 total enzyme,"},{"Start":"06:30.890 ","End":"06:33.425","Text":"which means this and this,"},{"Start":"06:33.425 ","End":"06:40.400","Text":"minus enzyme, and substrate formations times substrate concentration."},{"Start":"06:40.400 ","End":"06:44.450","Text":"That would be the rate of enzyme substrate formation"},{"Start":"06:44.450 ","End":"06:49.550","Text":"and the rate of the breakdown would be the k negative 1 going this direction"},{"Start":"06:49.550 ","End":"06:53.840","Text":"plus k_2 for enzyme substrate"},{"Start":"06:53.840 ","End":"06:59.635","Text":"because you\u0027re also getting the breakdown towards this direction."},{"Start":"06:59.635 ","End":"07:01.780","Text":"Now step 2,"},{"Start":"07:01.780 ","End":"07:05.780","Text":"we now make an important assumption that the initial rate of reaction reflects"},{"Start":"07:05.780 ","End":"07:10.205","Text":"a steady-state in which enzyme substrate concentration is a constant."},{"Start":"07:10.205 ","End":"07:11.960","Text":"That is the rate of formation of"},{"Start":"07:11.960 ","End":"07:15.710","Text":"enzyme substrate complex is equal to the rate of its breakdown,"},{"Start":"07:15.710 ","End":"07:19.520","Text":"and this is called the steady-state assumption."},{"Start":"07:19.520 ","End":"07:25.565","Text":"Step 3, in a series of algebraic steps that relate these parameters."},{"Start":"07:25.565 ","End":"07:30.150","Text":"While the term k negative 1 plus"},{"Start":"07:30.150 ","End":"07:37.800","Text":"k_2 over k_1 is defined as the Michaelis constant, k_m."},{"Start":"07:38.650 ","End":"07:42.650","Text":"This is introduced and the relationship can be"},{"Start":"07:42.650 ","End":"07:46.970","Text":"expressed as concentration of enzyme substrate equals"},{"Start":"07:46.970 ","End":"07:50.600","Text":"total enzyme concentration times substrate concentration"},{"Start":"07:50.600 ","End":"07:56.515","Text":"over the Michaelis constant plus substrate concentration."},{"Start":"07:56.515 ","End":"07:59.170","Text":"Now step 4,"},{"Start":"07:59.170 ","End":"08:03.785","Text":"we combine the equation we introduced before"},{"Start":"08:03.785 ","End":"08:08.945","Text":"and substitute the right side for enzyme substrate concentration."},{"Start":"08:08.945 ","End":"08:12.260","Text":"We can now express"},{"Start":"08:12.260 ","End":"08:17.150","Text":"initial velocity or reaction rate in terms of enzyme substrate concentration."},{"Start":"08:17.150 ","End":"08:22.605","Text":"We take this and we sub this n here."},{"Start":"08:22.605 ","End":"08:31.470","Text":"Now you have V naught equals k_2 times this entire thing,"},{"Start":"08:31.470 ","End":"08:37.155","Text":"and because it is multiplied by this entire thing, you have it."},{"Start":"08:37.155 ","End":"08:41.420","Text":"This actually can be written as such,"},{"Start":"08:41.420 ","End":"08:44.810","Text":"k_2 times concentration of total enzyme times concentration of"},{"Start":"08:44.810 ","End":"08:49.550","Text":"substrate over because constant plus substrate concentration."},{"Start":"08:49.550 ","End":"08:53.765","Text":"This equation can be further simplified."},{"Start":"08:53.765 ","End":"08:58.564","Text":"With this, we completed Part 1 of the Michaelis-Menten equation lesson"},{"Start":"08:58.564 ","End":"09:00.780","Text":"within the Chapter 1 on enzymes"},{"Start":"09:00.780 ","End":"09:03.520","Text":"and we learned how to describe the Michaelis-Menten equation,"},{"Start":"09:03.520 ","End":"09:05.615","Text":"explain the steady-state assumption,"},{"Start":"09:05.615 ","End":"09:09.690","Text":"and understand the derivation of the Michaelis-Menten equation."}],"ID":30149},{"Watched":false,"Name":"Michaelis Menten Equation Part 2","Duration":"7m 4s","ChapterTopicVideoID":28599,"CourseChapterTopicPlaylistID":286644,"HasSubtitles":true,"ThumbnailPath":null,"UploadDate":null,"DurationForVideoObject":null,"Description":null,"MetaTitle":null,"MetaDescription":null,"Canonical":null,"VideoComments":[],"Subtitles":[{"Start":"00:00.000 ","End":"00:04.635","Text":"Welcome to Part 2 of the lesson on Michaelis-Menten equation."},{"Start":"00:04.635 ","End":"00:06.120","Text":"By the end of this section,"},{"Start":"00:06.120 ","End":"00:08.721","Text":"you\u0027ll be able to describe Michaelis-Menten equation even better,"},{"Start":"00:08.721 ","End":"00:09.840","Text":"understand the derivation of"},{"Start":"00:09.840 ","End":"00:12.600","Text":"the Michaelis-Menten equation further and understand the terms;"},{"Start":"00:12.600 ","End":"00:16.635","Text":"initial velocity, maximum velocity and Michaelis constant."},{"Start":"00:16.635 ","End":"00:22.905","Text":"Maximum velocity occurs when the enzyme is saturated,"},{"Start":"00:22.905 ","End":"00:29.100","Text":"that is with enzyme substrate concentration equaling total enzyme because"},{"Start":"00:29.100 ","End":"00:35.900","Text":"all the enzyme is bound to substrate because there\u0027s so much more substrate than enzyme,"},{"Start":"00:35.900 ","End":"00:43.885","Text":"then Vmax can be defined as k_2 times total enzyme concentration,"},{"Start":"00:43.885 ","End":"00:47.405","Text":"so reminding you of the equation from the previous slide,"},{"Start":"00:47.405 ","End":"00:53.145","Text":"we can substitute Vmax as being k_2 times E_t, total enzyme."},{"Start":"00:53.145 ","End":"01:01.490","Text":"This can be substituted by Vmax and this results in this equation where you"},{"Start":"01:01.490 ","End":"01:04.330","Text":"have reaction rate equals"},{"Start":"01:04.330 ","End":"01:11.150","Text":"Vmax times substrate concentration over Michaelis constant plus substrate concentration."},{"Start":"01:11.150 ","End":"01:17.059","Text":"Now, this right here is the Michaelis-Menten equation,"},{"Start":"01:17.059 ","End":"01:22.475","Text":"the rate equation for a 1 substrate enzyme catalyzed reaction."},{"Start":"01:22.475 ","End":"01:28.175","Text":"It is a statement of the quantitative relationship between the initial velocity,"},{"Start":"01:28.175 ","End":"01:34.220","Text":"the maximum velocity, and the initial substrate concentration,"},{"Start":"01:34.220 ","End":"01:38.790","Text":"all related through the Michaelis constant K_m."},{"Start":"01:38.790 ","End":"01:43.110","Text":"Now note that K_m has units of concentration."},{"Start":"01:43.110 ","End":"01:48.755","Text":"But considering eliminate situation or substrate concentration is very low or very high."},{"Start":"01:48.755 ","End":"01:51.215","Text":"As shown in this figure,"},{"Start":"01:51.215 ","End":"01:55.475","Text":"you have substrate concentration either very low or very"},{"Start":"01:55.475 ","End":"01:58.400","Text":"high an important numerical relationship"},{"Start":"01:58.400 ","End":"02:01.865","Text":"emerges from the Michaelis-Menten equation in this special case,"},{"Start":"02:01.865 ","End":"02:11.545","Text":"when initial velocity or reaction rate is exactly 1/2 of Vmax."},{"Start":"02:11.545 ","End":"02:15.590","Text":"When reaction rate is exactly 1/2 of Vmax,"},{"Start":"02:15.590 ","End":"02:18.005","Text":"you have Vmax here,"},{"Start":"02:18.005 ","End":"02:21.560","Text":"half of that right here,"},{"Start":"02:21.560 ","End":"02:30.906","Text":"if you take this and equate it to Vmax half split by 2 and it equals,"},{"Start":"02:30.906 ","End":"02:34.840","Text":"then on dividing by Vmax,"},{"Start":"02:34.840 ","End":"02:37.781","Text":"take this you by Vmax,"},{"Start":"02:37.781 ","End":"02:40.435","Text":"you can cancel these out,"},{"Start":"02:40.435 ","End":"02:43.310","Text":"cancel this out so you have 1/2 and then you have"},{"Start":"02:43.310 ","End":"02:46.456","Text":"substrate concentration over K_m plus substrate concentration,"},{"Start":"02:46.456 ","End":"02:50.765","Text":"then you solve for K_m for the Michaelis concentration."},{"Start":"02:50.765 ","End":"02:58.355","Text":"Basically, you\u0027d have to multiply this side here so you\u0027d have"},{"Start":"02:58.355 ","End":"03:06.267","Text":"K_m substrate concentration over 2 equals substrate concentration,"},{"Start":"03:06.267 ","End":"03:09.295","Text":"then you multiply it by 2,"},{"Start":"03:09.295 ","End":"03:14.595","Text":"so you have K_m plus substrate concentration"},{"Start":"03:14.595 ","End":"03:20.923","Text":"equals 2 times substrate concentration and that is what you see here,"},{"Start":"03:20.923 ","End":"03:22.580","Text":"and then you substrate concentration,"},{"Start":"03:22.580 ","End":"03:26.465","Text":"you move it to the other side and you result in K_m"},{"Start":"03:26.465 ","End":"03:30.870","Text":"equals substrate concentration because you have 2 times S,"},{"Start":"03:30.870 ","End":"03:33.180","Text":"you have minus 1 S,"},{"Start":"03:33.180 ","End":"03:39.160","Text":"you remain with k_m equals substrate concentration, meaning K_m,"},{"Start":"03:39.160 ","End":"03:43.220","Text":"the Michaelis constant is equal to the substrate concentration when"},{"Start":"03:43.220 ","End":"03:49.150","Text":"the reaction rate is equal to half of the maximum velocity."},{"Start":"03:49.150 ","End":"03:52.080","Text":"When you see the low concentration,"},{"Start":"03:52.080 ","End":"03:53.785","Text":"so just talk about this figure,"},{"Start":"03:53.785 ","End":"03:58.455","Text":"dependence of initial velocity on substrate concentration,"},{"Start":"03:58.455 ","End":"04:02.330","Text":"this graph shows the kinetic parameters that define the limits of the curve at"},{"Start":"04:02.330 ","End":"04:08.840","Text":"high and low substrate concentration with the Michaelis constant,"},{"Start":"04:08.840 ","End":"04:13.820","Text":"the K_m is much greater than substrate concentration and"},{"Start":"04:13.820 ","End":"04:16.670","Text":"a substrate concentration term in the denominator of"},{"Start":"04:16.670 ","End":"04:22.250","Text":"the Michaelis-Menten equation becomes significant and at low substrate concentration,"},{"Start":"04:22.250 ","End":"04:28.505","Text":"K_m is much greater than the substrate concentration."},{"Start":"04:28.505 ","End":"04:31.250","Text":"Substrate concentration in the denominator of"},{"Start":"04:31.250 ","End":"04:34.907","Text":"the Michaelis-Menten equation becomes insignificant,"},{"Start":"04:34.907 ","End":"04:39.255","Text":"so you can eliminate this because it\u0027s insignificant."},{"Start":"04:39.255 ","End":"04:42.425","Text":"Then equation simplifies to be reactionary"},{"Start":"04:42.425 ","End":"04:46.473","Text":"equals Vmax times substrate concentration over K_m,"},{"Start":"04:46.473 ","End":"04:52.595","Text":"and V_0 exhibits a linear dependence on substrate concentration."},{"Start":"04:52.595 ","End":"04:54.875","Text":"The more substrate concentration grows,"},{"Start":"04:54.875 ","End":"05:00.620","Text":"you have a linear equation, a linear graph."},{"Start":"05:00.620 ","End":"05:03.650","Text":"At high substrate concentration,"},{"Start":"05:03.650 ","End":"05:07.761","Text":"where substrate concentration is much greater than K_m,"},{"Start":"05:07.761 ","End":"05:10.880","Text":"the K_m term in the denominator of"},{"Start":"05:10.880 ","End":"05:15.950","Text":"the Michaelis-Menten equation becomes insignificant and the equation"},{"Start":"05:15.950 ","End":"05:24.875","Text":"simplifies to V Naught equals Vmax because the minute you eliminate."},{"Start":"05:24.875 ","End":"05:28.640","Text":"You have this and in this case,"},{"Start":"05:28.640 ","End":"05:33.890","Text":"this has become insignificant over here compared to the substrate."},{"Start":"05:33.890 ","End":"05:38.154","Text":"You have Vmax over substrate,"},{"Start":"05:38.154 ","End":"05:41.405","Text":"these cancel out and you result in"},{"Start":"05:41.405 ","End":"05:48.280","Text":"reaction rate equals the maximum velocity of the reaction."},{"Start":"05:48.280 ","End":"05:53.765","Text":"This is consistent with the plateau observed at high substrate concentrations."},{"Start":"05:53.765 ","End":"05:58.280","Text":"The Michaelis-Menten equation is therefore consistent with observed dependence of"},{"Start":"05:58.280 ","End":"06:02.750","Text":"reaction rate on substrate concentration and the shape of the curve is"},{"Start":"06:02.750 ","End":"06:08.160","Text":"defined by the terms Vmax over K_m at"},{"Start":"06:08.160 ","End":"06:17.690","Text":"low substrate concentration and Vmax at high substrate concentration."},{"Start":"06:17.690 ","End":"06:19.160","Text":"Now this is a very useful,"},{"Start":"06:19.160 ","End":"06:20.930","Text":"practical definition of K_m."},{"Start":"06:20.930 ","End":"06:26.540","Text":"K_m is equivalent to the substrate concentration at which"},{"Start":"06:26.540 ","End":"06:34.165","Text":"velocity or reaction rate is 1/2 of Vmax."},{"Start":"06:34.165 ","End":"06:37.784","Text":"The Michaelis-Menten equation can be algebraic, the transform,"},{"Start":"06:37.784 ","End":"06:46.600","Text":"the two versions that are useful in the practical determination of K_m and Vmax."},{"Start":"06:46.600 ","End":"06:51.995","Text":"With this we completed the lesson on Michaelis-Menten equation within the chapter on"},{"Start":"06:51.995 ","End":"06:57.035","Text":"enzymes and you should be able to describe a Michaelis-Menten equation,"},{"Start":"06:57.035 ","End":"07:00.305","Text":"the steady-state assumption and the terms initial velocity,"},{"Start":"07:00.305 ","End":"07:04.500","Text":"maximum velocity and Michaelis constant."}],"ID":30150},{"Watched":false,"Name":"Exercise 4","Duration":"1m 40s","ChapterTopicVideoID":28600,"CourseChapterTopicPlaylistID":286644,"HasSubtitles":true,"ThumbnailPath":null,"UploadDate":null,"DurationForVideoObject":null,"Description":null,"MetaTitle":null,"MetaDescription":null,"Canonical":null,"VideoComments":[],"Subtitles":[{"Start":"00:00.000 ","End":"00:04.575","Text":"Let\u0027s apply an exercise to see our understanding of the Michaelis-Menten equation lesson."},{"Start":"00:04.575 ","End":"00:09.165","Text":"Explain the rate equation for one-substrate enzyme catalyzed reaction."},{"Start":"00:09.165 ","End":"00:11.700","Text":"The rate equation for one-substrate enzyme"},{"Start":"00:11.700 ","End":"00:15.100","Text":"catalyzed reaction is the Michaelis-Menten equation."},{"Start":"00:15.290 ","End":"00:22.670","Text":"It is a statement of the quantitative relationship between the initial velocity V_0,"},{"Start":"00:22.670 ","End":"00:27.920","Text":"the maximum velocity Vmax and the"},{"Start":"00:27.920 ","End":"00:33.755","Text":"initial substrate concentration [S] substrate,"},{"Start":"00:33.755 ","End":"00:38.315","Text":"and all are related through the Michaelis constant K_m."},{"Start":"00:38.315 ","End":"00:43.730","Text":"Now, note that KM has units of concentration."},{"Start":"00:43.730 ","End":"00:47.690","Text":"Again, the rate equation for a one-substrate enzyme"},{"Start":"00:47.690 ","End":"00:52.629","Text":"catalyzed reaction is called the Michaelis-Menten equation,"},{"Start":"00:52.629 ","End":"00:56.930","Text":"and it is a quantitative relationship that takes"},{"Start":"00:56.930 ","End":"01:02.645","Text":"the velocities of the reaction and these are initial and maximum velocity."},{"Start":"01:02.645 ","End":"01:04.745","Text":"Because if we think of the reaction,"},{"Start":"01:04.745 ","End":"01:07.490","Text":"the reaction takes place when we talked about the figure"},{"Start":"01:07.490 ","End":"01:10.100","Text":"that I could place here but I\u0027m actually going to draw it right now."},{"Start":"01:10.100 ","End":"01:12.780","Text":"When we look at the x axis,"},{"Start":"01:12.780 ","End":"01:14.759","Text":"we talk about substrate concentration,"},{"Start":"01:14.759 ","End":"01:17.390","Text":"and when we talk about the y axis we can talk"},{"Start":"01:17.390 ","End":"01:20.780","Text":"about initial velocity or let\u0027s just think about this as"},{"Start":"01:20.780 ","End":"01:24.950","Text":"velocity crossing the y axis of"},{"Start":"01:24.950 ","End":"01:31.505","Text":"the reaction and this changes with substrate concentration."},{"Start":"01:31.505 ","End":"01:38.920","Text":"Now, how these relate to each other is through the Michaelis constant, the K_m."}],"ID":30151},{"Watched":false,"Name":"Exercise 5","Duration":"1m 31s","ChapterTopicVideoID":28601,"CourseChapterTopicPlaylistID":286644,"HasSubtitles":true,"ThumbnailPath":null,"UploadDate":null,"DurationForVideoObject":null,"Description":null,"MetaTitle":null,"MetaDescription":null,"Canonical":null,"VideoComments":[],"Subtitles":[{"Start":"00:00.000 ","End":"00:03.585","Text":"Welcome to exercise within the Michaelis-Menten equation."},{"Start":"00:03.585 ","End":"00:05.265","Text":"Don\u0027t let the name scare you,"},{"Start":"00:05.265 ","End":"00:07.065","Text":"you know this material."},{"Start":"00:07.065 ","End":"00:09.735","Text":"Write and explain the Michaelis-Menten equation."},{"Start":"00:09.735 ","End":"00:12.293","Text":"The equation is Vmax,"},{"Start":"00:12.293 ","End":"00:17.445","Text":"maximum velocity times the substrate concentration over the Michaelis constant,"},{"Start":"00:17.445 ","End":"00:23.730","Text":"which is a constant that is established per enzyme plus the substrate concentration."},{"Start":"00:23.730 ","End":"00:29.100","Text":"Let\u0027s explain this. This equation is a quantitative algebraic expression of"},{"Start":"00:29.100 ","End":"00:35.145","Text":"the relationship between substrate concentration and reaction rate,"},{"Start":"00:35.145 ","End":"00:43.290","Text":"which would be either this or this because these both represent rate of reaction,"},{"Start":"00:43.290 ","End":"00:45.425","Text":"initial velocity and maximum velocity."},{"Start":"00:45.425 ","End":"00:49.070","Text":"The curve expressing the relationship between substrate concentration"},{"Start":"00:49.070 ","End":"00:53.270","Text":"and initial velocity has the same general shape for most enzymes."},{"Start":"00:53.270 ","End":"01:01.805","Text":"Or what you see is the idea that initially you have what is close to"},{"Start":"01:01.805 ","End":"01:06.800","Text":"a linear increase and this"},{"Start":"01:06.800 ","End":"01:09.225","Text":"is on the lower side of substrate concentration"},{"Start":"01:09.225 ","End":"01:11.910","Text":"and as you reach higher substrate concentrations,"},{"Start":"01:11.910 ","End":"01:15.170","Text":"the initial velocity reaches close to the Vmax."},{"Start":"01:15.170 ","End":"01:17.630","Text":"It is based on the hypothesis that the rate-limiting step in"},{"Start":"01:17.630 ","End":"01:21.110","Text":"enzymatic reactions is the breakdown of the ES,"},{"Start":"01:21.110 ","End":"01:22.580","Text":"the enzyme-substrate complex,"},{"Start":"01:22.580 ","End":"01:25.100","Text":"to product and free enzyme."},{"Start":"01:25.100 ","End":"01:30.810","Text":"That affects the rate at which the reaction occurs."}],"ID":30152},{"Watched":false,"Name":"Enzyme Kinetics Concepts","Duration":"8m 52s","ChapterTopicVideoID":28586,"CourseChapterTopicPlaylistID":286644,"HasSubtitles":true,"ThumbnailPath":null,"UploadDate":null,"DurationForVideoObject":null,"Description":null,"MetaTitle":null,"MetaDescription":null,"Canonical":null,"VideoComments":[],"Subtitles":[{"Start":"00:00.000 ","End":"00:03.495","Text":"We are within the chapter on enzymes,"},{"Start":"00:03.495 ","End":"00:05.378","Text":"within enzyme kinetics,"},{"Start":"00:05.378 ","End":"00:08.850","Text":"and we will now talk about enzyme kinetic concepts"},{"Start":"00:08.850 ","End":"00:12.660","Text":"because we introduced many and it is important that we very fully understand these."},{"Start":"00:12.660 ","End":"00:14.100","Text":"But the end of this section,"},{"Start":"00:14.100 ","End":"00:15.810","Text":"you\u0027ll be able to understand"},{"Start":"00:15.810 ","End":"00:18.585","Text":"the steady-state and maximum rate that we\u0027d already introduced,"},{"Start":"00:18.585 ","End":"00:23.770","Text":"the Michaelis-Menten equation and the Michaelis constant and enzyme inhibition."},{"Start":"00:24.170 ","End":"00:27.660","Text":"This is a summary of some of the concepts we already introduced,"},{"Start":"00:27.660 ","End":"00:30.750","Text":"as well as some main concepts that are important for the comprehension of"},{"Start":"00:30.750 ","End":"00:34.365","Text":"enzyme kinetics as an approach to understanding mechanisms."},{"Start":"00:34.365 ","End":"00:38.115","Text":"Most enzymes have certain kinetic properties in common."},{"Start":"00:38.115 ","End":"00:40.460","Text":"When substrate is added to an enzyme,"},{"Start":"00:40.460 ","End":"00:42.800","Text":"the reaction rapidly achieves a steady state"},{"Start":"00:42.800 ","End":"00:46.855","Text":"in which the rate at which the enzyme-substrate complex forms balances"},{"Start":"00:46.855 ","End":"00:49.230","Text":"the rate at which it reacts."},{"Start":"00:49.230 ","End":"00:51.620","Text":"As substrate concentration increases,"},{"Start":"00:51.620 ","End":"00:54.290","Text":"the steady-state activity of a fixed concentration of"},{"Start":"00:54.290 ","End":"00:58.490","Text":"enzyme increases in a hyperbolic fashion as seen here."},{"Start":"00:58.490 ","End":"01:02.365","Text":"To approach a characteristic maximum rate, V_max,"},{"Start":"01:02.365 ","End":"01:06.919","Text":"at which essentially all the enzyme has formed a complex with substrate,"},{"Start":"01:06.919 ","End":"01:10.190","Text":"it is saturated with substrate because the concentration of"},{"Start":"01:10.190 ","End":"01:13.840","Text":"substrate is so much higher than enzyme."},{"Start":"01:13.840 ","End":"01:17.540","Text":"The substrate concentration that results in a reaction rate equal to"},{"Start":"01:17.540 ","End":"01:22.115","Text":"1.5 V_max is the Michaelis constant,"},{"Start":"01:22.115 ","End":"01:28.085","Text":"K_m, which is characteristic for each enzyme acting on a given substrate."},{"Start":"01:28.085 ","End":"01:32.435","Text":"Now, the Michaelis-Menten equation, as seen here,"},{"Start":"01:32.435 ","End":"01:37.130","Text":"relates initial velocity to substrate concentration,"},{"Start":"01:37.130 ","End":"01:42.730","Text":"and V_max through the K_m, the constant K_m."},{"Start":"01:42.730 ","End":"01:48.820","Text":"But Michaelis-Menten kinetics is also called steady-state kinetics."},{"Start":"01:48.820 ","End":"01:53.278","Text":"K_m and V_max have different meanings for different enzymes,"},{"Start":"01:53.278 ","End":"01:58.369","Text":"meaning the actual measure will be different for different enzymes."},{"Start":"01:58.369 ","End":"02:03.175","Text":"The limiting rate of an enzyme-catalyzed reaction at saturation is described by"},{"Start":"02:03.175 ","End":"02:08.580","Text":"the constant K_cat prime, the turnover number."},{"Start":"02:08.580 ","End":"02:12.380","Text":"This is something we hadn\u0027t introduced thus far."},{"Start":"02:12.380 ","End":"02:18.365","Text":"This is the constant that represents the turnover number."},{"Start":"02:18.365 ","End":"02:26.110","Text":"Now, reversible inhibition of an enzyme is competitive, uncompetitive or mixed."},{"Start":"02:26.110 ","End":"02:31.993","Text":"Competitive inhibitors compete with substrate by binding reversibly to the active site,"},{"Start":"02:31.993 ","End":"02:37.055","Text":"but they are not transformed by the enzyme because they\u0027re not actually the substrate."},{"Start":"02:37.055 ","End":"02:41.270","Text":"They bind to the active site and block"},{"Start":"02:41.270 ","End":"02:47.135","Text":"the actual substrate from binding the enzyme so product is not formed"},{"Start":"02:47.135 ","End":"02:53.570","Text":"and thus this inhibits the reaction from occurring and this is considered competitive"},{"Start":"02:53.570 ","End":"02:57.020","Text":"inhibition because the substrate is"},{"Start":"02:57.020 ","End":"03:01.745","Text":"blocked by an inhibitor that competed for the same site."},{"Start":"03:01.745 ","End":"03:05.255","Text":"Reversible inhibition of an enzyme can be competitive."},{"Start":"03:05.255 ","End":"03:08.850","Text":"This is the example of such a case."},{"Start":"03:08.850 ","End":"03:13.010","Text":"Uncompetitive inhibitors which bind only to the ES complex,"},{"Start":"03:13.010 ","End":"03:14.960","Text":"the enzyme-substrate complex,"},{"Start":"03:14.960 ","End":"03:17.720","Text":"at a site distinct from the active site."},{"Start":"03:17.720 ","End":"03:20.315","Text":"This would be the idea of the allosteric site."},{"Start":"03:20.315 ","End":"03:22.730","Text":"You have an inhibitor that binds at a different site than"},{"Start":"03:22.730 ","End":"03:25.580","Text":"the active site and thus results in"},{"Start":"03:25.580 ","End":"03:28.310","Text":"some conformational change of the enzyme so that"},{"Start":"03:28.310 ","End":"03:31.910","Text":"this doesn\u0027t form efficiently, it falls apart."},{"Start":"03:31.910 ","End":"03:37.380","Text":"The substrate doesn\u0027t stay bound to the enzyme within the enzyme-substrate complex."},{"Start":"03:37.380 ","End":"03:41.780","Text":"Then you have mixed inhibitors which bind to either the enzyme or"},{"Start":"03:41.780 ","End":"03:46.545","Text":"the enzyme-substrate again at a site distinct from the active site."},{"Start":"03:46.545 ","End":"03:49.160","Text":"Uncompetitive inhibitors only on"},{"Start":"03:49.160 ","End":"03:52.400","Text":"a different site on the ES complex and mixed inhibitors bind to"},{"Start":"03:52.400 ","End":"03:54.290","Text":"either the enzyme on its own or"},{"Start":"03:54.290 ","End":"03:58.760","Text":"the enzyme-substrate complex at a distinct site from the active site,"},{"Start":"03:58.760 ","End":"04:02.620","Text":"which is why it can bind either-or."},{"Start":"04:02.620 ","End":"04:05.040","Text":"In irreversible inhibition,"},{"Start":"04:05.040 ","End":"04:08.990","Text":"an inhibitor binds permanently to an active site by forming"},{"Start":"04:08.990 ","End":"04:14.150","Text":"a covalent bond or a very stable non-covalent interaction,"},{"Start":"04:14.150 ","End":"04:19.070","Text":"and thus blocks the actual substrate from binding to"},{"Start":"04:19.070 ","End":"04:24.620","Text":"the enzyme because the active site is blocked in an irreversible fashion."},{"Start":"04:24.620 ","End":"04:32.825","Text":"Now, every enzyme has an optimum pH or pH range at which it has maximal activity."},{"Start":"04:32.825 ","End":"04:36.890","Text":"We touched upon this in previous lessons."},{"Start":"04:36.890 ","End":"04:40.100","Text":"What you see here are 2 different enzymes,"},{"Start":"04:40.100 ","End":"04:43.535","Text":"pepsin and glucose 6-phosphatase."},{"Start":"04:43.535 ","End":"04:46.595","Text":"This may sounds familiar because we use this as an example."},{"Start":"04:46.595 ","End":"04:48.470","Text":"We have the y-axis,"},{"Start":"04:48.470 ","End":"04:51.028","Text":"in this case is the log of the reaction rate,"},{"Start":"04:51.028 ","End":"04:53.955","Text":"and the x-axis is pH."},{"Start":"04:53.955 ","End":"04:55.790","Text":"You have for pepsin,"},{"Start":"04:55.790 ","End":"04:57.958","Text":"an acidic pH, it\u0027s below 7,"},{"Start":"04:57.958 ","End":"05:00.920","Text":"and for glucose-6 phosphatase,"},{"Start":"05:00.920 ","End":"05:02.495","Text":"you have a basic pH,"},{"Start":"05:02.495 ","End":"05:06.050","Text":"all starting at a little bit of acidic because it\u0027s a little below 6."},{"Start":"05:06.050 ","End":"05:10.595","Text":"Now, this is the pH activity of pH activity profiles of these 2 enzymes."},{"Start":"05:10.595 ","End":"05:13.580","Text":"These curves are constructed from measurements of"},{"Start":"05:13.580 ","End":"05:17.990","Text":"initial velocities when the reaction is carried out in buffers of different pH."},{"Start":"05:17.990 ","End":"05:22.640","Text":"You allow the reaction to occur in different pH and you measure the rate."},{"Start":"05:22.640 ","End":"05:25.940","Text":"Because pH is a logarithmic scale reflecting 10-fold changes"},{"Start":"05:25.940 ","End":"05:29.480","Text":"in proton concentration of hydrogen plus,"},{"Start":"05:29.480 ","End":"05:34.450","Text":"the changes in reaction rate are also plotted here on a logarithm scale."},{"Start":"05:34.450 ","End":"05:37.490","Text":"The pH optimum for the activity of an enzyme is"},{"Start":"05:37.490 ","End":"05:41.030","Text":"generally close to the pH of the environment in which the enzyme is normally found."},{"Start":"05:41.030 ","End":"05:42.935","Text":"If we\u0027re talking about pepsin as in A,"},{"Start":"05:42.935 ","End":"05:47.810","Text":"which hydrolyzes certain peptide bonds or proteins during digestion in the stomach,"},{"Start":"05:47.810 ","End":"05:52.310","Text":"it has a pH optimum about 1.6."},{"Start":"05:52.310 ","End":"05:59.645","Text":"This is because it\u0027s in the summit and the pH of gastric juice is between 1 and 2."},{"Start":"05:59.645 ","End":"06:08.790","Text":"The environment is 1 that it sits between 1 and 2 and its optimal V_max or"},{"Start":"06:08.790 ","End":"06:14.840","Text":"the 100 percent reaction rate or activity is close to"},{"Start":"06:14.840 ","End":"06:21.500","Text":"the average in the middle of the actual pH environment in which it is found."},{"Start":"06:21.500 ","End":"06:24.145","Text":"In the case of glucose 6-phosphatase,"},{"Start":"06:24.145 ","End":"06:26.285","Text":"b of this figure,"},{"Start":"06:26.285 ","End":"06:29.885","Text":"you have this enzyme that works on hepatocytes,"},{"Start":"06:29.885 ","End":"06:34.240","Text":"meaning liver cells with a pH optimum of about"},{"Start":"06:34.240 ","End":"06:43.830","Text":"7.8 of the 100 percent almost activity or V_max."},{"Start":"06:43.830 ","End":"06:49.205","Text":"It is responsible for releasing glucose into the blood."},{"Start":"06:49.205 ","End":"06:53.840","Text":"When the normal pH of the cytosol of hepatocytes of these liver cells is"},{"Start":"06:53.840 ","End":"06:58.310","Text":"about 7.2, this explains it."},{"Start":"06:58.310 ","End":"07:01.400","Text":"Now, these 2 enzymes can be familiar because we"},{"Start":"07:01.400 ","End":"07:05.645","Text":"introduced a previous figure when we talked about this,"},{"Start":"07:05.645 ","End":"07:11.870","Text":"where we mentioned pepsin and we mentioned phosphatase,"},{"Start":"07:11.870 ","End":"07:14.195","Text":"although it was alkaline phosphatase."},{"Start":"07:14.195 ","End":"07:17.495","Text":"But still very similar,"},{"Start":"07:17.495 ","End":"07:24.305","Text":"you have this to be higher because it\u0027s a basic phosphatase."},{"Start":"07:24.305 ","End":"07:27.650","Text":"You have pepsin, as we said,"},{"Start":"07:27.650 ","End":"07:29.915","Text":"in about 1.6,"},{"Start":"07:29.915 ","End":"07:32.855","Text":"and we also gave the example of trypsin,"},{"Start":"07:32.855 ","End":"07:37.170","Text":"where it sits at a little above 6."},{"Start":"07:37.170 ","End":"07:39.000","Text":"Now this is not surprising."},{"Start":"07:39.000 ","End":"07:43.010","Text":"Amino acid change in the active site may act as weak acids and bases"},{"Start":"07:43.010 ","End":"07:47.300","Text":"with critical functions that depend on their maintaining a certain state of ionization."},{"Start":"07:47.300 ","End":"07:49.910","Text":"Elsewhere in the protein ionized side chains may play"},{"Start":"07:49.910 ","End":"07:53.315","Text":"an essential role in the interactions that maintain protein structure."},{"Start":"07:53.315 ","End":"07:57.169","Text":"Removing a proton from a certain residue, for example,"},{"Start":"07:57.169 ","End":"07:59.210","Text":"might eliminate an ionic interaction"},{"Start":"07:59.210 ","End":"08:02.765","Text":"essential for stabilizing the active conformation of the enzyme."},{"Start":"08:02.765 ","End":"08:08.450","Text":"Thus, different pHs can completely deactivate an enzyme."},{"Start":"08:08.450 ","End":"08:13.130","Text":"Now the pH range over which an enzyme undergoes changes in"},{"Start":"08:13.130 ","End":"08:18.575","Text":"activity can provide a clue to the type of amino acid residue involved,"},{"Start":"08:18.575 ","End":"08:24.335","Text":"as well as the environment that the enzyme optimally resides and functions in."},{"Start":"08:24.335 ","End":"08:28.820","Text":"A change in activity near pH 7, for example,"},{"Start":"08:28.820 ","End":"08:33.570","Text":"often reflects titration of a his residue,"},{"Start":"08:33.570 ","End":"08:35.520","Text":"a histidine residue,"},{"Start":"08:35.520 ","End":"08:38.409","Text":"this is just an FYI."},{"Start":"08:38.409 ","End":"08:44.220","Text":"We completed enzyme kinetics concepts, and at this point,"},{"Start":"08:44.220 ","End":"08:46.430","Text":"we covered steady-state and maximum rate,"},{"Start":"08:46.430 ","End":"08:51.900","Text":"the Michaelis-Menten equation and Michaelis constant, and enzyme inhibition."}],"ID":30153},{"Watched":false,"Name":"Exercise 6","Duration":"1m 45s","ChapterTopicVideoID":28587,"CourseChapterTopicPlaylistID":286644,"HasSubtitles":true,"ThumbnailPath":null,"UploadDate":null,"DurationForVideoObject":null,"Description":null,"MetaTitle":null,"MetaDescription":null,"Canonical":null,"VideoComments":[],"Subtitles":[{"Start":"00:00.000 ","End":"00:05.010","Text":"Welcome to an exercise with an enzyme kinetics concepts."},{"Start":"00:05.010 ","End":"00:10.380","Text":"Explain the steady-state and maximum rate and how these relate."},{"Start":"00:10.380 ","End":"00:16.020","Text":"These are concepts that we introduced in previous lessons and now we\u0027re connecting them."},{"Start":"00:16.020 ","End":"00:18.570","Text":"When substrate is added to an enzyme,"},{"Start":"00:18.570 ","End":"00:23.940","Text":"the reaction rapidly achieves a steady-state in which the rate at which the ES complex,"},{"Start":"00:23.940 ","End":"00:25.590","Text":"the enzyme substrate complex,"},{"Start":"00:25.590 ","End":"00:30.015","Text":"forms balances the rate at which it reacts."},{"Start":"00:30.015 ","End":"00:33.510","Text":"Again, when substrate is added to an enzyme,"},{"Start":"00:33.510 ","End":"00:37.245","Text":"remember we even mentioned of a pre-steady state in the previous section,"},{"Start":"00:37.245 ","End":"00:40.920","Text":"the reaction rapidly achieves a steady-state in which the rate at which the ES"},{"Start":"00:40.920 ","End":"00:45.985","Text":"complex forms balances the rate at which it reacts."},{"Start":"00:45.985 ","End":"00:48.860","Text":"As substrate concentration increases,"},{"Start":"00:48.860 ","End":"00:51.620","Text":"the steady-state activity of a fixed concentration of"},{"Start":"00:51.620 ","End":"00:57.785","Text":"enzyme increases in a hyperbolic fashion to approach a characteristic maximum rate,"},{"Start":"00:57.785 ","End":"01:03.620","Text":"V_max, at which essentially all the enzyme has formed a complex with substrate."},{"Start":"01:03.620 ","End":"01:06.355","Text":"Reminding you, looking at the figure,"},{"Start":"01:06.355 ","End":"01:08.710","Text":"as substrate concentration increases,"},{"Start":"01:08.710 ","End":"01:11.540","Text":"the steady-state activity of a fixed concentration of"},{"Start":"01:11.540 ","End":"01:18.275","Text":"enzyme increases in a hyperbolic fashion to approach a characteristic maximum rate,"},{"Start":"01:18.275 ","End":"01:20.115","Text":"the V_max, and at that point,"},{"Start":"01:20.115 ","End":"01:22.550","Text":"all the enzyme has formed a complex with substrate."},{"Start":"01:22.550 ","End":"01:27.800","Text":"We assume here, we can presume that all the enzyme is"},{"Start":"01:27.800 ","End":"01:30.080","Text":"saturated with substrate because there\u0027s"},{"Start":"01:30.080 ","End":"01:34.120","Text":"high enough concentration of substrate to saturate all of the enzyme."},{"Start":"01:34.120 ","End":"01:36.080","Text":"We generally talked about how"},{"Start":"01:36.080 ","End":"01:42.320","Text":"the substrate concentration is generally much greater than the enzyme concentration."},{"Start":"01:42.320 ","End":"01:45.360","Text":"With that, we completed this exercise."}],"ID":30154},{"Watched":false,"Name":"Exercise 7","Duration":"2m 11s","ChapterTopicVideoID":28588,"CourseChapterTopicPlaylistID":286644,"HasSubtitles":true,"ThumbnailPath":null,"UploadDate":null,"DurationForVideoObject":null,"Description":null,"MetaTitle":null,"MetaDescription":null,"Canonical":null,"VideoComments":[],"Subtitles":[{"Start":"00:00.000 ","End":"00:04.049","Text":"Welcome to another exercise with an enzyme kinetics concepts."},{"Start":"00:04.049 ","End":"00:06.705","Text":"What is the Michaelis constant?"},{"Start":"00:06.705 ","End":"00:13.460","Text":"The substrate concentration that results in a reaction rate equal to one half of V_max,"},{"Start":"00:13.460 ","End":"00:15.660","Text":"this point right here,"},{"Start":"00:15.660 ","End":"00:18.030","Text":"is the Michaelis constant,"},{"Start":"00:18.030 ","End":"00:22.020","Text":"designated K subscript m, K_m."},{"Start":"00:22.020 ","End":"00:28.815","Text":"This Michaelis constant is characteristic for each enzyme acting on a given substrate."},{"Start":"00:28.815 ","End":"00:31.695","Text":"When reactions are measured,"},{"Start":"00:31.695 ","End":"00:35.925","Text":"the velocity for a specific enzyme and a specific substrate,"},{"Start":"00:35.925 ","End":"00:42.285","Text":"there is a rate of velocity for that reaction and it is typical for that reaction."},{"Start":"00:42.285 ","End":"00:46.760","Text":"When the half of V_max is reached for that reaction,"},{"Start":"00:46.760 ","End":"00:49.470","Text":"that is the K_m,"},{"Start":"00:49.470 ","End":"00:52.170","Text":"that is the Michaelis constant."},{"Start":"00:52.170 ","End":"00:56.330","Text":"This is something that can be looked up as it was"},{"Start":"00:56.330 ","End":"01:00.920","Text":"established per reaction of enzyme on a given substrate."},{"Start":"01:00.920 ","End":"01:08.060","Text":"Furthermore, we mention this as something that is part of the Michaelis-Menten equation."},{"Start":"01:08.060 ","End":"01:13.590","Text":"I remind you, this is a rate equation for a one substrate enzyme catalyzed reaction,"},{"Start":"01:13.590 ","End":"01:19.070","Text":"meaning that for that one substrate and that one enzyme,"},{"Start":"01:19.070 ","End":"01:25.440","Text":"if we can call the enzyme mike and the substrate it works on is ike,"},{"Start":"01:25.440 ","End":"01:28.410","Text":"for mike and ike,"},{"Start":"01:28.410 ","End":"01:34.905","Text":"there will be a specific K_m and this reflects it."},{"Start":"01:34.905 ","End":"01:40.790","Text":"The reaction velocity of mike and ike has been established and measured."},{"Start":"01:40.790 ","End":"01:47.670","Text":"They found the half V_max of that reaction and that is the K_m."},{"Start":"01:47.670 ","End":"01:51.620","Text":"To remind you, the Michaelis-Menten equation is basically"},{"Start":"01:51.620 ","End":"01:54.650","Text":"an algebraic representation that is"},{"Start":"01:54.650 ","End":"01:59.105","Text":"a quantitative relationship between the initial velocity,"},{"Start":"01:59.105 ","End":"02:04.830","Text":"the maximum velocity, the substrate concentration,"},{"Start":"02:04.830 ","End":"02:11.370","Text":"and they\u0027re all related through the Michaelis constant."}],"ID":30155},{"Watched":false,"Name":"Exercise 8","Duration":"4m 17s","ChapterTopicVideoID":28589,"CourseChapterTopicPlaylistID":286644,"HasSubtitles":true,"ThumbnailPath":null,"UploadDate":null,"DurationForVideoObject":null,"Description":null,"MetaTitle":null,"MetaDescription":null,"Canonical":null,"VideoComments":[],"Subtitles":[{"Start":"00:00.000 ","End":"00:08.415","Text":"Welcome to another exercise to establish our knowledge on enzyme kinetics concepts."},{"Start":"00:08.415 ","End":"00:10.590","Text":"What is the Michaelis-Menten equation,"},{"Start":"00:10.590 ","End":"00:13.690","Text":"and what relationship does it depict?"},{"Start":"00:13.790 ","End":"00:15.945","Text":"We just touched upon this."},{"Start":"00:15.945 ","End":"00:23.340","Text":"The Michaelis-Menten equation relates initial velocity to substrate concentration,"},{"Start":"00:23.340 ","End":"00:28.155","Text":"and maximum velocity through the constant K_m, which is what?"},{"Start":"00:28.155 ","End":"00:31.270","Text":"This is the Michaelis constant."},{"Start":"00:31.270 ","End":"00:32.930","Text":"Let\u0027s try to think about it."},{"Start":"00:32.930 ","End":"00:35.690","Text":"I want you to try to remember how these relate."},{"Start":"00:35.690 ","End":"00:39.875","Text":"The Michaelis-Menten equation starts with"},{"Start":"00:39.875 ","End":"00:46.730","Text":"initial velocity equaling what is on the numerator and what\u0027s in the denominator."},{"Start":"00:46.730 ","End":"00:50.330","Text":"Well, we do know that hopefully, you remember this,"},{"Start":"00:50.330 ","End":"00:54.155","Text":"that substrate concentration are found in both."},{"Start":"00:54.155 ","End":"00:57.230","Text":"But, if they\u0027re found in both,"},{"Start":"00:57.230 ","End":"00:59.705","Text":"it means that N1,"},{"Start":"00:59.705 ","End":"01:04.190","Text":"it is a product and N1 it is addition."},{"Start":"01:04.190 ","End":"01:11.090","Text":"So V_max, what is related to our V_max in a direct proportional manner,"},{"Start":"01:11.090 ","End":"01:13.685","Text":"and that is velocity."},{"Start":"01:13.685 ","End":"01:22.190","Text":"V_max is on top here and it\u0027s the product of this that relates initial velocity."},{"Start":"01:22.620 ","End":"01:25.000","Text":"If we think about it,"},{"Start":"01:25.000 ","End":"01:29.305","Text":"remember our x-axis, that is our substrate concentration."},{"Start":"01:29.305 ","End":"01:35.756","Text":"Our y-axis is our V_0, our initial velocity."},{"Start":"01:35.756 ","End":"01:39.370","Text":"As substrate concentration increases,"},{"Start":"01:39.370 ","End":"01:42.370","Text":"initial velocity starts with almost linear,"},{"Start":"01:42.370 ","End":"01:44.170","Text":"and then it starts to plateau."},{"Start":"01:44.170 ","End":"01:46.865","Text":"Where does it start to plateau?"},{"Start":"01:46.865 ","End":"01:54.640","Text":"Close to the V_max when substrate concentration is very high."},{"Start":"01:54.640 ","End":"02:02.300","Text":"V_max times substrate concentration reflects initial velocity."},{"Start":"02:02.300 ","End":"02:04.400","Text":"What does this mean if substrate concentration,"},{"Start":"02:04.400 ","End":"02:06.573","Text":"if you have 0,"},{"Start":"02:06.573 ","End":"02:08.670","Text":"1, 2, 4, 5,"},{"Start":"02:10.090 ","End":"02:13.715","Text":"and initial velocity is,"},{"Start":"02:13.715 ","End":"02:17.009","Text":"I\u0027m just going to keep it simple now, 10, 20,"},{"Start":"02:17.009 ","End":"02:23.935","Text":"30, 40, blah-blah-blah, 100?"},{"Start":"02:23.935 ","End":"02:30.469","Text":"If you are going to say you have V_max of a 100,"},{"Start":"02:30.469 ","End":"02:32.410","Text":"is it about 4?"},{"Start":"02:32.410 ","End":"02:33.980","Text":"That means it\u0027s 400,"},{"Start":"02:33.980 ","End":"02:38.285","Text":"and initial velocity will be whatever,"},{"Start":"02:38.285 ","End":"02:41.210","Text":"400 divided by whatever is at the bottom."},{"Start":"02:41.210 ","End":"02:46.720","Text":"Now here it\u0027s going to"},{"Start":"02:46.720 ","End":"02:54.485","Text":"be 500 because 5 and the velocity hasn\u0027t changed much."},{"Start":"02:54.485 ","End":"02:57.080","Text":"V_max is the same rate."},{"Start":"02:57.080 ","End":"02:58.640","Text":"The V_max doesn\u0027t change,"},{"Start":"02:58.640 ","End":"03:00.455","Text":"so you have a 100 times 5,"},{"Start":"03:00.455 ","End":"03:03.500","Text":"which is the substrate concentration."},{"Start":"03:03.500 ","End":"03:05.045","Text":"If we think about it,"},{"Start":"03:05.045 ","End":"03:09.062","Text":"at substrate concentration 4 times V_max is 400,"},{"Start":"03:09.062 ","End":"03:11.330","Text":"at substrate concentration of 5,"},{"Start":"03:11.330 ","End":"03:14.885","Text":"it\u0027s 500 times V_max."},{"Start":"03:14.885 ","End":"03:17.420","Text":"No matter what it means,"},{"Start":"03:17.420 ","End":"03:19.160","Text":"the initial velocity is growing."},{"Start":"03:19.160 ","End":"03:21.875","Text":"It\u0027s a direct relationship."},{"Start":"03:21.875 ","End":"03:26.720","Text":"As we\u0027re changing, we\u0027re seeing the initial velocity it is growing a"},{"Start":"03:26.720 ","End":"03:31.385","Text":"little bit because here it\u0027s a little higher."},{"Start":"03:31.385 ","End":"03:35.360","Text":"That\u0027s a reminder that the Michaelis constant is down"},{"Start":"03:35.360 ","End":"03:40.820","Text":"here and it is plus the substrate concentration."},{"Start":"03:40.820 ","End":"03:43.660","Text":"Cleaning this all up,"},{"Start":"03:43.660 ","End":"03:47.841","Text":"Michaelis meant an equation is V_0"},{"Start":"03:47.841 ","End":"03:54.420","Text":"= V_max times [S]/K_m+[S]."},{"Start":"03:54.420 ","End":"03:57.345","Text":"This is all saying it\u0027s"},{"Start":"03:57.345 ","End":"04:00.875","Text":"a 1 substrate enzyme reaction that"},{"Start":"04:00.875 ","End":"04:04.970","Text":"is reflected through an algebraic quantitative equation,"},{"Start":"04:04.970 ","End":"04:09.815","Text":"which is the Michaelis-Menten equation and it relates the initial velocity"},{"Start":"04:09.815 ","End":"04:17.220","Text":"to maximum velocity and substrate concentration through the Michaelis constant."}],"ID":30156},{"Watched":false,"Name":"Exercise 9","Duration":"5m 49s","ChapterTopicVideoID":28590,"CourseChapterTopicPlaylistID":286644,"HasSubtitles":true,"ThumbnailPath":null,"UploadDate":null,"DurationForVideoObject":null,"Description":null,"MetaTitle":null,"MetaDescription":null,"Canonical":null,"VideoComments":[],"Subtitles":[{"Start":"00:00.000 ","End":"00:04.575","Text":"We have another exercise within enzyme kinetics concepts."},{"Start":"00:04.575 ","End":"00:09.915","Text":"Really hope these ideas are sinking in your mind."},{"Start":"00:09.915 ","End":"00:11.700","Text":"Which statement is false?"},{"Start":"00:11.700 ","End":"00:16.215","Text":"A, Michaelis-Menten kinetics is also called steady-state kinetics."},{"Start":"00:16.215 ","End":"00:20.515","Text":"B, K_m and V_max have different meanings for different enzymes."},{"Start":"00:20.515 ","End":"00:24.300","Text":"C, The limiting rate of an enzyme catalyzed reaction at saturation"},{"Start":"00:24.300 ","End":"00:28.515","Text":"is described as the constant k_cat, the turnover number."},{"Start":"00:28.515 ","End":"00:31.350","Text":"D, Every enzyme has an optimum pH,"},{"Start":"00:31.350 ","End":"00:36.945","Text":"or pH range at which it has maximal activity and E, all of the above."},{"Start":"00:36.945 ","End":"00:39.580","Text":"Let\u0027s go by these one by one."},{"Start":"00:39.580 ","End":"00:42.230","Text":"Which statement is false?"},{"Start":"00:42.230 ","End":"00:43.805","Text":"We\u0027re going to this one at a time."},{"Start":"00:43.805 ","End":"00:49.055","Text":"A, Michaelis-Menten kinetics is also called steady-state kinetics."},{"Start":"00:49.055 ","End":"00:56.690","Text":"We did talk about Michaelis-Menten kinetics having to do with the steady-state."},{"Start":"00:56.690 ","End":"00:58.745","Text":"And that\u0027s what we talked about in this lesson."},{"Start":"00:58.745 ","End":"01:00.230","Text":"So in this lesson,"},{"Start":"01:00.230 ","End":"01:01.790","Text":"we actually talked about,"},{"Start":"01:01.790 ","End":"01:08.780","Text":"and related steady-state kinetics to the idea of the Michaelis-Menton equation,"},{"Start":"01:08.780 ","End":"01:11.795","Text":"and kinetics that we introduced in previous lessons."},{"Start":"01:11.795 ","End":"01:16.490","Text":"What can we say? We basically said that when substrate is added to enzyme,"},{"Start":"01:16.490 ","End":"01:17.780","Text":"the reaction mark of the achieves"},{"Start":"01:17.780 ","End":"01:22.325","Text":"a steady-state in which the rate at which the enzyme substrate complex forms,"},{"Start":"01:22.325 ","End":"01:24.500","Text":"balances the rate at which it reacts."},{"Start":"01:24.500 ","End":"01:28.820","Text":"All this is to say that as substrate concentration increases,"},{"Start":"01:28.820 ","End":"01:30.725","Text":"the steady-state activity of fixed concentration of"},{"Start":"01:30.725 ","End":"01:34.970","Text":"enzyme increases in a fashion to approach characteristic maximum rate,"},{"Start":"01:34.970 ","End":"01:40.445","Text":"the V_max at which essentially all the enzyme has formed a complex with substrate."},{"Start":"01:40.445 ","End":"01:46.115","Text":"This is all related to the Michaelis-Menten equation and thus,"},{"Start":"01:46.115 ","End":"01:50.080","Text":"these are also related,"},{"Start":"01:50.080 ","End":"01:53.090","Text":"and Michaelis-Menten kinetics is also called a steady-state kinetics,"},{"Start":"01:53.090 ","End":"01:54.530","Text":"and therefore this is true."},{"Start":"01:54.530 ","End":"01:56.090","Text":"So this is not our answer."},{"Start":"01:56.090 ","End":"02:01.519","Text":"Let\u0027s go on to B, K_m and V_max have different meanings for different enzymes."},{"Start":"02:01.519 ","End":"02:06.540","Text":"Well, yeah, they have a K_m for a different enzyme."},{"Start":"02:06.540 ","End":"02:11.272","Text":"It will be different with a specific substrate than with a different substrate,"},{"Start":"02:11.272 ","End":"02:12.710","Text":"and if you look at the same substrate,"},{"Start":"02:12.710 ","End":"02:18.830","Text":"the K_m for that same substrate with having two different enzymes will be different."},{"Start":"02:18.830 ","End":"02:20.300","Text":"Now if that was confusing,"},{"Start":"02:20.300 ","End":"02:24.000","Text":"let\u0027s say enzyme we\u0027ve talked about Mike before."},{"Start":"02:24.100 ","End":"02:32.985","Text":"Substrate mike will have a K_m of x."},{"Start":"02:32.985 ","End":"02:38.520","Text":"Now if you have an enzyme called Bike."},{"Start":"02:38.520 ","End":"02:42.495","Text":"Even if it\u0027s reacting with the same substrate,"},{"Start":"02:42.495 ","End":"02:46.385","Text":"Ike, it\u0027s K_m will be different."},{"Start":"02:46.385 ","End":"02:52.093","Text":"Its K_m will be y. K_m will be different for different enzymes,"},{"Start":"02:52.093 ","End":"02:58.685","Text":"and in essence being that it relates V_max or K_m is half the V_max."},{"Start":"02:58.685 ","End":"03:02.930","Text":"Also V_max for a specific enzyme and substrate will be"},{"Start":"03:02.930 ","End":"03:08.195","Text":"different than the V_max for a different enzyme and a substrate,"},{"Start":"03:08.195 ","End":"03:11.317","Text":"even if it\u0027s a different enzyme with the same substrate."},{"Start":"03:11.317 ","End":"03:14.600","Text":"This is true and therefore, it\u0027s correct."},{"Start":"03:14.600 ","End":"03:18.110","Text":"Let\u0027s go with C. The limiting rate of an enzyme"},{"Start":"03:18.110 ","End":"03:22.220","Text":"catalyzed reaction at saturation is described by the constant K_cat,"},{"Start":"03:22.220 ","End":"03:23.915","Text":"which is the turnover number."},{"Start":"03:23.915 ","End":"03:28.865","Text":"This is something we introduced in this lesson and we mentioned it briefly,"},{"Start":"03:28.865 ","End":"03:32.870","Text":"but explained it as mentioned here."},{"Start":"03:32.870 ","End":"03:34.640","Text":"This again is a true statement."},{"Start":"03:34.640 ","End":"03:38.740","Text":"Therefore, it\u0027s not our false statement, it\u0027s not our answer."},{"Start":"03:38.740 ","End":"03:45.710","Text":"D, every enzyme has an optimum pH or pH range at which it has maximal activity."},{"Start":"03:45.710 ","End":"03:48.200","Text":"We touched upon this in a few lectures,"},{"Start":"03:48.200 ","End":"03:50.840","Text":"and we reiterated it here and here specifically,"},{"Start":"03:50.840 ","End":"03:55.040","Text":"we introduced a new figure showing similar things and that figure showed"},{"Start":"03:55.040 ","End":"04:00.610","Text":"pepsin in a and phosphatase,"},{"Start":"04:00.610 ","End":"04:05.300","Text":"specifically glucose-6 phosphatase in the other figure that we"},{"Start":"04:05.300 ","End":"04:11.690","Text":"introduced and it showed a different range of maximum activity."},{"Start":"04:11.690 ","End":"04:16.895","Text":"The V naught for both at maximum."},{"Start":"04:16.895 ","End":"04:20.825","Text":"We look here versus here,"},{"Start":"04:20.825 ","End":"04:23.435","Text":"was at different pH ranges."},{"Start":"04:23.435 ","End":"04:30.350","Text":"Where pepsin was in acidic range and I think we mentioned, if you remember,"},{"Start":"04:30.350 ","End":"04:38.760","Text":"about 1.6 is maximal activity or 100% activity for phosphatase."},{"Start":"04:38.760 ","End":"04:41.130","Text":"For glucose-6 phosphatase,"},{"Start":"04:41.130 ","End":"04:46.365","Text":"we saw this to be closer to 8."},{"Start":"04:46.365 ","End":"04:48.455","Text":"For 8 was about here."},{"Start":"04:48.455 ","End":"04:50.570","Text":"Maybe it was at 7.8 or so."},{"Start":"04:50.570 ","End":"04:58.715","Text":"It\u0027s more in a neutral leading to the basic pH and the activity is within that range."},{"Start":"04:58.715 ","End":"05:00.844","Text":"This is the range of activity."},{"Start":"05:00.844 ","End":"05:05.392","Text":"We can say here is a good range word still quite active,"},{"Start":"05:05.392 ","End":"05:07.670","Text":"and it could be saying between,"},{"Start":"05:07.670 ","End":"05:10.865","Text":"let\u0027s say 5 and 10 or whatnot."},{"Start":"05:10.865 ","End":"05:16.890","Text":"This again, and we join it with additional figures in previous lessons."},{"Start":"05:16.890 ","End":"05:18.410","Text":"This is a correct statement,"},{"Start":"05:18.410 ","End":"05:20.000","Text":"therefore it\u0027s not false."},{"Start":"05:20.000 ","End":"05:23.370","Text":"E, All of the above."},{"Start":"05:23.370 ","End":"05:25.230","Text":"Are they all false?"},{"Start":"05:25.230 ","End":"05:29.135","Text":"Well, this would be in this case,"},{"Start":"05:29.135 ","End":"05:31.990","Text":"our correct answer because this is false."},{"Start":"05:31.990 ","End":"05:34.460","Text":"Because none of them are false. They\u0027re all true."},{"Start":"05:34.460 ","End":"05:39.110","Text":"Saying that all of the above or false is false at an essence,"},{"Start":"05:39.110 ","End":"05:42.620","Text":"this is a false statement and if that was confusing, that\u0027s okay."},{"Start":"05:42.620 ","End":"05:45.335","Text":"The bottom line was for you to see that these are"},{"Start":"05:45.335 ","End":"05:49.800","Text":"all correct statements that we covered in this lesson."}],"ID":30157},{"Watched":false,"Name":"Exercise 10","Duration":"3m 21s","ChapterTopicVideoID":28591,"CourseChapterTopicPlaylistID":286644,"HasSubtitles":true,"ThumbnailPath":null,"UploadDate":null,"DurationForVideoObject":null,"Description":null,"MetaTitle":null,"MetaDescription":null,"Canonical":null,"VideoComments":[],"Subtitles":[{"Start":"00:00.000 ","End":"00:04.425","Text":"Welcome back to another exercise with an enzyme kinetics concepts."},{"Start":"00:04.425 ","End":"00:09.105","Text":"Explain enzyme inhibition and the various types mentioned in the lesson."},{"Start":"00:09.105 ","End":"00:15.450","Text":"We have reversible inhibition of an enzyme which is competitive, uncompetitive or mixed."},{"Start":"00:15.450 ","End":"00:20.130","Text":"Reversible inhibition is inhibition that can be reversed,"},{"Start":"00:20.130 ","End":"00:23.205","Text":"and it can be competitive, uncompetitive or mixed."},{"Start":"00:23.205 ","End":"00:26.550","Text":"Competitive inhibitors compete with substrate,"},{"Start":"00:26.550 ","End":"00:29.130","Text":"but binding reversibly to the active site,"},{"Start":"00:29.130 ","End":"00:31.860","Text":"but they are not transformed by the enzyme."},{"Start":"00:31.860 ","End":"00:38.855","Text":"You have inhibitors that compete with the substrate for the active site of the enzyme."},{"Start":"00:38.855 ","End":"00:41.660","Text":"By binding that active site, it is blocking."},{"Start":"00:41.660 ","End":"00:46.720","Text":"It\u0027s inhibiting the substrate from binding to the active site of the enzyme,"},{"Start":"00:46.720 ","End":"00:50.090","Text":"and therefore the enzyme cannot carry out the reaction,"},{"Start":"00:50.090 ","End":"00:52.820","Text":"and the inhibitor isn\u0027t transformed by the enzyme."},{"Start":"00:52.820 ","End":"00:56.795","Text":"What does that mean? The enzyme doesn\u0027t use it as a substrate."},{"Start":"00:56.795 ","End":"01:01.250","Text":"There is no reaction that occurs that takes this inhibitor,"},{"Start":"01:01.250 ","End":"01:05.120","Text":"and turns it into a different product."},{"Start":"01:05.120 ","End":"01:06.650","Text":"It doesn\u0027t transform it to anything."},{"Start":"01:06.650 ","End":"01:09.275","Text":"The inhibitor just stays the inhibitor."},{"Start":"01:09.275 ","End":"01:14.390","Text":"Uncompetitive inhibitor is another form of inhibition that is reversible."},{"Start":"01:14.390 ","End":"01:17.660","Text":"Uncompetitive inhibitors bind only to the ES complex,"},{"Start":"01:17.660 ","End":"01:21.740","Text":"the enzyme substrate complex at a site distinct from the active site."},{"Start":"01:21.740 ","End":"01:23.780","Text":"It could be an allosteric site."},{"Start":"01:23.780 ","End":"01:26.458","Text":"This term was introduced in the previous lesson,"},{"Start":"01:26.458 ","End":"01:27.860","Text":"and we iterate in this one."},{"Start":"01:27.860 ","End":"01:31.010","Text":"Uncompetitive inhibitors bind only to the ES complex,"},{"Start":"01:31.010 ","End":"01:35.075","Text":"the enzyme substrate complex at a different site from the active site."},{"Start":"01:35.075 ","End":"01:40.740","Text":"But, it inhibits the enzyme substrate reaction,"},{"Start":"01:40.740 ","End":"01:42.485","Text":"or this transition state,"},{"Start":"01:42.485 ","End":"01:49.405","Text":"or this transition product to then complete reaction and the have the product released."},{"Start":"01:49.405 ","End":"01:54.590","Text":"Then have a third type of reversible inhibition and that is mixed inhibitors."},{"Start":"01:54.590 ","End":"01:57.910","Text":"These are ones that bind to either the enzyme,"},{"Start":"01:57.910 ","End":"01:59.705","Text":"or the enzyme substrate complex."},{"Start":"01:59.705 ","End":"02:06.555","Text":"Again, like the uncompetitive inhibitors at a site distinct from the active site."},{"Start":"02:06.555 ","End":"02:08.660","Text":"You have the uncompetitive inhibitors,"},{"Start":"02:08.660 ","End":"02:13.540","Text":"and the mixed inhibitors that bind at a different site from the active site,"},{"Start":"02:13.540 ","End":"02:15.965","Text":"while the competitive inhibitors,"},{"Start":"02:15.965 ","End":"02:23.810","Text":"they compete with the substrate by binding the actual active site of the enzyme."},{"Start":"02:23.810 ","End":"02:28.180","Text":"The second form of inhibition that we introduced is irreversible inhibition,"},{"Start":"02:28.180 ","End":"02:30.230","Text":"that means it can\u0027t be reversed."},{"Start":"02:30.230 ","End":"02:38.350","Text":"Something happens and the enzyme can no longer be reversed to bind substrate and react."},{"Start":"02:38.350 ","End":"02:42.650","Text":"Irreversible inhibition is in the case when an inhibitor"},{"Start":"02:42.650 ","End":"02:47.060","Text":"binds permanently to an active site by forming a covalent bond,"},{"Start":"02:47.060 ","End":"02:50.225","Text":"or a very stable non-covalent interaction."},{"Start":"02:50.225 ","End":"02:54.650","Text":"This irreversible inhibition occurs by an inhibitor that binds"},{"Start":"02:54.650 ","End":"02:58.640","Text":"to the active site of the enzyme, in strong bond,"},{"Start":"02:58.640 ","End":"03:01.550","Text":"either a very stable non-covalent interaction,"},{"Start":"03:01.550 ","End":"03:06.740","Text":"or a covalent bond that now it does not disconnect."},{"Start":"03:06.740 ","End":"03:11.135","Text":"It does not just disassociate from the enzyme, and therefore,"},{"Start":"03:11.135 ","End":"03:16.460","Text":"it doesn\u0027t allow the enzyme to bind substrate and catalyze a reaction,"},{"Start":"03:16.460 ","End":"03:20.820","Text":"and therefore it is irreversible inhibition."}],"ID":30158}],"Thumbnail":null,"ID":286644}]

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