Biochemistry Chapter 15: Metabolism PDF

Chapter 15 all right now in the previous discussions we've learned of the characteristics the properties as well as the processes undergone by Major biological molecules the um the proteins the uh carbohydrates the lipids and the most recent discussions the nucleic acids today we're going to...

Chapter 15 all right now in the previous discussions we've learned of the characteristics the properties as well as the processes undergone by Major biological molecules the um the proteins the uh carbohydrates the lipids and the most recent discussions the nucleic acids today we're going to focus our attention on um very dense and a very um diverse um topic and that is metabolism you have encountered metabolism in one way or another in the academic setting and perhaps even in Social settings where you hear the word 00:00:49 metabolism and so on so forth this is topic but but you will more likely encounter say for example if you're if you're on a diet if you're um Consulting a die dis or if you're going to the gym you're trying to lose weight and U trying to build muscles all right metabolism is the sum total of all the chemical reactions that occur in the body I think I have to qualify that statement it is the sum total of all those chemical reactions that are intended to harness energy and also um what are intended to 00:01:30 build build to build um molecules simple building blocks like amino acids like sugars from substances that are either taken in by an individual from its environment say for example the food that you taken or um from metabolites which are already present in your system in the living system in today's discussion we're going to consider metabolism and pay attention also to the energetics of the chemical reactions involved in in metabolic processes okay now um consider following all right so as you can see we're now in chapter 15 of 00:02:20 chapter 15 of Campell and phro the biochemistry we're going to look at the importance of energy changes and electron transfer in metabolism this is an introductory topic this is an introductory topic to um more detailed discussions on glycolysis the crab cycle the electron transfer chain the pentos phosphate pathway the um different metabolic pathway of the syntheses of amino acids as well as for the oxidation of lipids like fats synthesis of lipids and so on so forth so these are this is a core introductory talk topic for 00:03:01 understanding more complex um um subjects later so today we're going to discuss these introductory topics and also um push on to push um and uh discuss the process of glycolysis as well all right so we're going to tackle two chapters today okay so as I've mentioned we're going to consider the energy changes as we see the the bolic reactions and the energy changes associated with such reactions are typically measured with the actions carried out in the standard States so it is important that you are made familiar 00:03:42 to standard States or what are standard States okay now let me use my laser pointer so standard States uh correspond to um it's um an agreed upon agreed upon state with which or with which all or based on which all thermodynamic properties are going to be measured and it varies from from one state of matter to another for Pure solids and liquids standard state is a pure substance for gases it is the gas behaving as an ideal gas at a pressure of one atmosphere for Solutions it is an ideal solution at a concentration of one 00:04:27 mole per liter in other words one unit marity so for example for reaction AA plus BB forming CC and then DD products you can write um um an equation characteris for that particular reaction where we say it Delta G Delta G is the change in free energy associated with the reaction is equal to Delta G not it is the standard um gives fee energy change in other words it's the gives free energy for of a substance measured in the standard states in the standard state or when all substances are involved in their action 00:05:07 or in their standard State plus RT natural logarithm of um um the ratios of the concentrations of the um product C raised to smaller or C the coefficient in the balanced chemical equation times a concentration of D raised to D divided concentration of a raed to a and concentration of B raed to D by way we call this ratio very action quotient so you will notice that um apologize I think my neighbor is doing some repair so the um um the value of a Delta G then is dependent upon upon the um ratios of this um of this 00:05:52 um concentration race of their respective Powers um the important thing that we have to discuss now each zero in is the standard gives free energy change by the way when the reaction has a negative um gibes free energy change that means that the reaction is spontaneous what does it mean it means that the reaction proceeds on its own it just happens you do not need to make it happen it just happens and the negative um value of energy indicates that it releases an amount of energy equal to that value for example 00:06:33 if this reaction has a Delta G of -10 K per mole and that means that the reaction occurs spontaneously and that it releases 10 KJ of energy if it is the opposite that is if it is positive the GES three energy change is positive then the reaction does not occur and that you have to put in energy equal to 10 KJ in order for reaction to proceed okay that's when it's negative it is spontaneous when it is positive it is non-spontaneous another term for that is exergonic and endergonic when the reaction has a negative Delta G when the 00:07:14 reaction is said to be exergonic and it occurs one generously when the reaction is a positive Del G the reaction is endergonic and you need to um Supply an amount of energy equal to the Delta G in order to make it happen all right all right now let's go back to that PowerPoint presentation all right so our goal is to t zero in on the values of the Delta G not so the value that we need to focus on now as I've mentioned is the value of a Delta G not and the value of a Delta G not that corresponds to the standard um 00:07:54 gives energy change okay um there is one problem however and what is that problem the problem is that as I've mentioned before for the standard Gibs energy changes if you have a solution you have to have a concentration that's equal to one molar right that's problematic for reactions carried out in in the body because the concentration of the hydrogen ion in the body is not one molar one molar first to a pH equal to zero right and that pH is very very low you do not um your your blood for example or the biological 00:08:34 fluids do not have a pH equal to equal to um um equal to zero it has a pH that is equal to seven right so in that case we need to um take that into account and instead of taking the values of Delta G instead of taking the values of Delta G um and saying that it's equal to um um one mol we say that it is equal to say that it is equal to 10^ the -7 for the for the um hydrogen ion concentration all right and okay so in that case we have to adjust all of the values that you have obtained in the literature and instead of referring to 00:09:30 it Delta G note Delta G note we call that Delta G not prime um later I'm going to show you a table of Delta G values for now I want to again emphasize the fact that since we're considering phological um systems that is um reactions that occur in the body where the pH is typically seven the Delta G is measured not at one molar hydrogen ion concentration but at 10 to A7 mol right the usual thermodynamic standards that it implies that the system involv is at pH Z which is seldom if ever found in living things because that's not AR 00:10:12 offical pH the modified standard St explicitly States the system is at ph7 all right I hope that um that is clear all right now let us um proceive okay the um reactions that we are going to consider the metabolic reactions we're going to consider typically are simply reactions that harness energy right it it involves a conversion of one form of energy to another and you can therefore trace it in one way or another from the energy of the sun like you see here energy of the sun which are actually come from 00:11:03 nuclear reactions are happening in the sun Fusion reactions areen happening in the sun such energy captured by plants in the process of photosynthesis right where carbon dioxide and water are converted into glucose all right and the process the Plants release oxygen as well now heterotrophs such as ourselves take up or take take in glucose and oxygen and the proc process we exhale carbon dioxide we Bend Water now this is what we call metabolism that part of the energy diagram it's the sum total of all 00:11:41 those reactions that are involving the oxidation of food or of nutrient like in this case glucose um to uh to uh carbon dioxide in water all right now the energy in this case is captured in the form of a Denine triphosphate that's why we call it the energy currency of a cell if you remember back in biology um it's always said that ATP is the energy currency of a cell because that's essentially what you need to have in order to make reactions happen in living systems even the process of DNA replication right as well as the process 00:12:20 of of DNA of of transcription DNA transcription in fact translation all of the processes that we have encountered so far um I'm not saying all but most of them are energy requiring and all of these let's say 99% of these will require the consumption of a Denine trios okay so the energy is captured in the form of a Denine triphosphate metabolism and this ATP is then used up in the synthesis of what biological molecules like amino acids um what else um sugars um proteins nucleic acids and so on so forth right that's 00:13:08 the tendency so in effect we as organisms are harnessing energy from the Sun allbe it through um intermediate like processes like photosynthesis okay now metabolism as I've mentioned it's chemical reactions of bi molecues so it's it's a sum total of all this chemical reactions and U um the ability of living systems to uh replicate and to reproduce must have been coupled with the ability to uh to metabolize energy sources otherwise um the process of replication could not have could not have occurred 00:13:54 right there has to be some time in the evolutionary past where this to metabolism and and and replication or ability to reproduce must have um intersected and the first living organisms have exhibited Thea characteristics of reproduction as well as metabolism now catabolism and anabolism so catabolism refers to a breakdown of larger molecules into smaller ones right this is an oxidative process that release energy while anabolism refers to the synthesis of larger molecules from smaller molecules 00:14:37 it's a reductive process requires energy so notice that catabolism releases energy or anabolism um uses up energy all right okay now as I've mentioned metabolism is the sum total of all the chemical reactions of biological molecules in an organism as you can see here the nutrients for example that you take in fats the polysaccharides for example you eat um what's fat um pork fat for example like eat that fat polysaccharide what is poly starch starch which is the main component of rice right and uh proteins the pork meat 00:15:21 for example excuse me when you eat take in the substances the substances are catabolized all right catabolized into their component fatty acids and glycerol for example for fats component glucose and other monosaccharides for polysaccharides and component amino acids for proteins all right now this um small molecules rather this um building blocks are further oxidized into smaller molecules and uh the smaller molecules are then um the smaller molecules are then further catabolized and uh some of them have are 00:16:11 assimilated by the cell and used in the syesis of of other molecules like in anabolic reactions okay that U aim to synthesize amino acids for example or the pamine and the um purine bases for for example okay so as we mentioned here catabolism then oxidative uh um the oxidation of the um building blocks into smaller molecules and then that smaller molecules are either excreted or are used in anabolic reactions okay in anabolism some nutrients and the products of catabolism are employed so to not worry we're going to go to the 00:16:58 details of that in future succeeding discussions the um the um so the nutrients and the products of of catabolism are assimilated or appropriated and used up in cesis of some other biological molecules in a reductive process so this requires reducing agents and this require energy all right the um products of anabolism include proteins and nuic acids now you will notice that catabolism and analism are opposed to each other right they are opposed to each other the catabolism refers to the breakdown 00:17:40 of bigger molecules into smaller molecules the process releasing energy while anabolism refers to the to the um cesis of more complicated molecules from from smaller molecules and this process requires energy okay um okay so you have mentioned or you have heard me mention the word oxidation or rather oxidative and reductive naturally these are derived from the words oxidation and reduction right I hope that you still remember what this term means like in general chemistry or not in general chemistry 00:18:22 from organic chemistry oxidation reduction reactions are those in which electrons are transferred from a donor to an receptor so when a substance loses an electron that substance is said to have undergone oxidation when substance um excepts an electron that substance is said to have undergone reduction all right undergone reduction so oxidation is the loss of electrons the substance that loses the electrons is called a reducing agent it is a reducing agent because in the process of losing an electron in other words in the process 00:18:56 of being oxidized it causes the reduction of the other substance reduction is a gain of electrons so the substance that is undergoing reduction in being reduced is actually acting as an oxidizing agent all right okay now oxidation is accompanied by release of energy and this energy is typically captured in the form of a Denine triphosphate in catabolic reactions reduction reactions on the other hand these are anabolic reactions and this are typically the energy requiring reactions okay now the carbon in its 00:19:34 most reduced form is alkane like you know what an alkane is alkane is where you have carbon bonded to hydrogen for example methane is an alkane CH4 other examples of alkanes are ethane propane and so on so forth like these are saturated car compounds organic compounds contain just carbon and hydrogen carbon in its most oxidized form is carbon dioxide this is the final product of catabolism that's one with heterotrophs such as ourselves exhale out right so there is a lot of energy lot of chemical energy stored in the carbon 00:20:16 hydrogen bond as well as the carbon carbon Bond okay but there's little energy stored in the carbon oxygen double bond that is why from ch2 for example it's oxidized to this substance Co cbond o carboxilic acid and ultimately two carbon dioxide so you have an alkane oxidize into an alcohol oxidize into an alide or a ketone into a carboxilic acid and then ultimately to carbon dioxide this process from the alkane to carbon dioxide is oxidation and that process reduces energy while the opposite is 00:20:56 reduction and that process the opposite process requires energy for it to happen okay all right now now look at that consider this reaction right zinc solid plus copper 2+ forming zinc 2+ and then copper solid notice that the copper 2+ here has undergone reduction it is reduced right because it accepted electron from zinc and so like this is the half reaction this is the reduction half reaction you have copper 2 plus plus two electrons forming copper so copper two plus is said to be the oxidizing agent because it is 00:21:40 undergone reduction therefore causes the oxidation of the other substance what is that other substance that other substance is zinc zinc lost an electron so it is undergone oxidation in the process reducing the copper 2 plus so zinc is an example of a reducing agent right if we can determine the concentration of reactants and products at the equilibrium we can determine keq or the equilibrium constant again this is something that you've already discussed or learned in general chemistry and from it change in free 00:22:17 energy for conversion of one Mo of reactant product okay now and how um in catabolism as I've mentioned in summary large molecules are broken down to smaller products and this process is typically accompanied by release of energy and this energy is captured in the form of a Denine triphosphate in anabolism small molecules react to give more complicated molecules bigger molecules and this um reactions typically energy requiring in this case instead of actually um forming ATP in the process you actually consume ATP all 00:22:59 right okay now now these are the co-enzymes which are typically used in biologically important reactions um for example conversion of ethanol to acetal deide is a two electron oxidation reaction why do we say two electron oxidation because it loses the ethanol to acetal deide it loses two electons you see here this is ethanol this is acetal deide produce two electrons as a result as well as 2 H+ the um as I was saying the oxidation of ethanol to acetal deide is an example of a two electron oxidation reaction and 00:23:43 this is what happen say for example if I don't know if you drink alcohol but this is what happens when you drink alcohol you um oxidize ethanol into acetal deide acetal deide is a poison right well it's a toxic substance and that um um you what happens to you when you drink alcohol you turn red right some develops allergy and perhaps the most important the most obvious effect of drinking alcohol is intoxication this the term itself suggests that there's something toxic within you right intoxication you're being intoxicated 00:24:29 the intoxicating effect of alcohol is attributable to acetal behive right okay that is that's something that you have to bear in mind um I'm not sure if you're familiar if you know that but women who are pregnant should not be drinking alcohol because ethanol that is oxidized to acetal dhide crosses I mean the the ethanol which is oxidized to acetal dhide um the acetal dhide that is formed crosses the placenta from the mother to the fetus all right and the fetus remember AET alide is toxic all right so it tends to kill the child or 00:25:12 the fetus or to cause um defamations so if you if uh if you have somebody if you know somebody who pregnant now please tell her not to consume alcohol okay so going back the oxidation this is an example of an oxidation reaction right um you uh um lose two electrons see that ethanol there are 12 electrons in groups involved in the reaction like in this group right 2 4 6 8 10 12 in AET alide there are just 10 electrons in GR in groups involved in their reaction 2 4 6 8 10 so notice that it is indeed an 00:26:00 oxidation in the two electrons are lost all right now this sort of reaction like oxidation reactions actually require the participation of co-enzymes this co-enzymes are themselves acting as oxidizing agents or reducing agents as a case may be since you already have here an oxidation reaction then somebody has or some some something has to be oxidizing that right and that something is actually n a plus nuide add incle gain don't worry we're going to consider the structure going to learn more about that later this is just 00:26:42 an introduction bear that in mind is an important co-enzyme now a coenzyme is a molecule that is needed by an enzyme to perform its function there are two molecules or groups of of such um such classification the co-enzymes and the co-actors right the difference between the co-enzymes and the co-actors that the co-enzymes typically are small organic molecules that can be can be um reversibly dissociated from the enzyme itself in other words they are not coent linked to the enzyme while the co-actors 00:27:21 are typically either um either metals or molecules that are um coal linked to the uh to the enzyme specifically in the active side okay now this in this case NAD plus acts as a biological oxidizing agent all right um NAD plus is the two electron oxidizing agent and it is reduced nadh in the process again um do not worry this I'm showing you the structure of the pomide addine dinucleotide I will not ask you to memorize the structure no good comes from memorization remember that so you have to understand what this means and 00:28:08 the relevance to this in our discussion this is nicotinamide adenine dcle or n plus okay notice that it's actually we've already discussed nucleotides right and what do you notice it's called a d nucleotide because there are two nucleotides this is one nucleotide remember a nucleotide consists of a base a sugar and a phosphate group so this is the adenine right the adenine base the ribos sugar as well as a phosphate group so this is um one nucleotide what about the other this is the other nucleotide 00:28:51 okay you have a phosphate group sugar and the other nitrogenous base in this case this is the nicotinamide ring right and I have to tell you that the molecule is quite huge right the molecule is quite long and it's quite big but only this portion of the molecule is actually important for the oxidation reduction reaction because in that case the hydride the H minus attacks this carbon causing the localization of electrons to this carbon and then to this nitrogen N1 so see now I have a lone pair at this 00:29:30 nitrogen this is if this is n a D+ this is n a DH all right nadh why is it called nadh because if you're going to notice you have one additional hydrogen right it actually AR there in the form of a hydride H minus right when you're going to ask yourselves if if you why then the need for a huge molecule the only important portion of the molecule is this point okay now that is a valid question the use or or the reason why the molecule is quite long is because this part this part serves as a handle serves as a handle for the enzyme 00:30:15 like it it is the part of a molecule that is anchored or if it serves as a handle or as an Anchorage Point as an Anchorage point to um um once the once the um coenzyme is um docked in the enzym substrate okay so yes only this part is important for catalysis or for very reaction rather but the entire molecule is needed because this portion is the one that is um serving as a handle for binding to the enzyme active side okay all right so what happens ethanol is oxidized for example into acet alide with two 00:31:05 electrons and the hydrogen ion you know what actually let me write that down hopefully this will work sometimes it doesn't work so you have H what I'm talking about is this we call this the hydride okay now the hydride as youve already mentioned a while ago see here H+ and then two electrons actually what happens there is that what you have here what you form here right is actually an H+ plus h minus H minus and where does the H minus come from remember you have one here H+ right H+ plus two electrons that becomes H minus 00:32:09 we call that a hydride all right a hydde um okay I'm not going to write that down because it's malfunctioning it's called a hydride all right okay so H minus is a hydride and that hydride is the one which actually um attacked this carbon carbon number four of the nicotinamide dring all right causing by the localization of electrons from here to between carbon five and six and the delocalization of electrons to N1 okay all right this is another example of um um of of of a of a co-enzyme like the 00:32:56 flavine adding dcle Ty right but this coenzyme is actually a pratic group right this is a prospe group in the sense that it is actually coal linked to the enzyme itself remember the case of NAD plus n ADH it actually reversibly binds and unbinds um from the enzyme the case of fad and fadh2 is different because this substance is actually Co valent linked to the enzyme right so this is another example of um of an oxidizing agent you have the flavine this is the oxidized form of flavine and it is the reduced form of flavine addine 00:33:40 dinucleotide again what we're showing here it's just the flavine ring right because again it's a dinucleotide flavine adenine dinucleotide it's like nicotinamide Adine dcle right in this case we're just showing the the group in the molecule that is important for per reaction and notice that What's Happening Here is that what happens you have the hydride attacks this nitrogen and the proton H+ um bonds to this nitrogen atoms you have here H and H fad fadh2 now fad and fadh2 as well as NAD and nadh are important in the process 00:34:27 called beta oxidation of fatty acids right it's important also in the crab cycle I'm not sure if you've heard of that but from what I remember there was a commercial a long time ago where you have they have this carnitine know carnitine have you heard of that carnitin that I think it's still available in the market so carnitine is a is an important molecule that is implicated in the transport of fatty acid and the oxidation of fatty acids right and it's important um for burning up fats and unless I'm mistaken in that 00:35:08 commercial they were trying to advertise it and then say that you're it's going to help you U become thinner and I I will not say that that is um effective but I I will say that there is a there is um there is a basis for that but I'm not sure if that actually works I don't know I haven't tried that so all right so this is now the structure of flavine adenine dinucleotide so you see here this is adenine again adenine this is the nucleotide for adenine and this is the flavine um the flavine ring so 00:35:52 it's an ISO aloine ring all right if you have a add nucleotide so it's this is it's this one the entire thing right if you have flavine mononucleotide then you just have from here up to there from here up to the phosphate group notice the sugar used here is not ribos but ribitol right ribitol okay again this is important this coenzyme is important for oxidation reduction reaction this is acting as um in this case or however in this case this is acting as an oxidizing agent but of course can also lose electrons the 00:36:35 process converting the fadh2 to fad plus the same is true with the nicotinamide right we have we have shown here NAD plus becoming nadh but the truth is nadh can be converted can be oxidized into NAD Plus in the process reducing electrons that case n acts as a reducing agent right now as I've mentioned before the process of metabolism involves the production of energy and the consumption of energy right a reaction has to have a net negative Delta G in order for it to happen many reactions in the body 00:37:21 actually have positive Dage and so how how how how do living systems make them happen or able to make them happen or at least our cells are able to make them happen by coupling them with exergonic reactions for example you have a reaction that is endergonic it's 10 KJ per mole it's Delta G not prime how do you make it happen we said that it it's not spontaneous We Make It Happen by couling it in other words with um a reaction that is more exergonic then then that reaction is endergonic in other words you can couple it with a 00:38:02 reaction that has A5 just an example5 KJ per mole Delta G Prime and so when you add up this two values Delta G Prime you're going to end up with 10 + -15 that's -5 so that's now overall overall um exer on it that's exactly what's happening in the cell right the sum total of all reactions that are happening in our cell right at this very moment have negative Dage he otherwise they will not haveen fact that they are happening means that they are spontaneous okay now as a whole they are spontaneous as a whole the coupling of 00:38:45 energy producing and energy requiring actions is a central theme in the metabolism of all organisms energy cannot useed directly but must be shuttled into easily accessible form forms of chemical energy and this is I've been saying or I've been alluding to this um um a number of times already remember me saying energy captured in the form of ATP that's exactly what it means you're um you're not using the energy for example from glucose directly but you're oxidizing glucose slowly into intermediates and in this process or or 00:39:27 along along the path along the um along the pathway you harness the energy that you can and use it in the synthesis of ATP this adenosine triphosphate is very useful because it is used in powering all of the important reactions in the body so high energy bonds these are the bonds that require or release convenient amount of energies depending on the direction of the reaction so ATP adenosine triphosphate is essential high energy Bond containing compound right as uh you're going to learn later the 00:40:06 phosphorilation of adenosine diphosphate to ATP requires energy and that's exactly what we harness in glycolysis energy I mean I mean that's exactly how we synthesize ADP cover ATP from ADP and inorganic phosphate the process of glycolysis we harness the energy coming from the oxidation of glucose right the opposite however the hydrolysis of ATP to ADP releases energy okay all right this are the this is the structure of a Denine triphosphate and see again you have an addine you have a sugar and you 00:40:46 have here excuse me triphosphate ATP um this notice consists of negative look at that this is a triphosphate group right and it is negatively charged you see that it is negatively charged so negative negative negative what do you expect you expect this group and therefore this entire substance to be very unstable why because you have a negative charge that is adjacent to another negative charge that is adjacent to another negative charge so that means that this substance is very unstable and what do you remember 00:41:28 remember that instability is associated with energy the more unstable the substance is high higher is its energy and vice versa the higher of energy the substance the more unstable it is the more reactive it is you notice that it's the same with people the more um the more higher and the the more unstable people are actually more energetic right if you are just going to find your inner piece then you're going to be stable right and you you're you're you're at a low energy State the same with molecules molecules that are that 00:42:11 have high energy are very unstable and therefore very reactive okay so um this is a high energy phosphoric anhydride Bond so this is an hydde that's a phosphoric and hydde another phosphoric and hydde okay H remember that the hydris of this bonds releases energy and it is that energy that is used in powering up the many different ATP requiring reactions in the body okay now look at that there are four negative charges in ATP and free on ADP therefore as I've mentioned ADP is less stable ATP is more reactive it has 00:43:01 a higher energy okay okay now energy must be expended to put on additional negative charge on ADP in other words if you want if you have here ADP that's that is a Denine di phosphate if you want to add a third phosphate here and produce ADP you will have to expand energy right and that energy again is captured rather is contain from the oxidation of nutrients like glucose for example okay um also entropy loss when ADP is phosphorated entropy is loss when ADP is phosphorated because there's a potential loss of 00:43:42 resonance hybridization of inorganic phosphate like here um okay um this is the um inorganic phosphate right inorganic phosphate inorganic phosphate inorganic phosphate notice that once it is converted into ATP um the the number of resonance structures that you can write then for inorganic phosphate diminishes and therefore that suggest that the substance ATP is less stable all right it is less stable okay now ATP hydrolysis what is hydrolysis it's the decompos of a molecule in the presence of water Hydro 00:44:32 Lis Hydro means water Lis means decomposition so water causing decomposition of a substance like hydrolysis or hydrolysis of ATP water causing the decomposition of ATP decreases electrostatic repulsion look at that as I've mentioned you have two negative charges one negative charge one negative charge this is unstable it's like you're putting an analogy will be you're you're trying to to put three individuals that to not want to have anything to do with each other right beside each other right you're putting 00:45:08 them right next to each other and that is a very unstable State of Affairs so um in the case of hydrolysis the um ADP for example is hydrolized into ADP ien in D phosphate one of the phosphate group has been removed and so the negative charges the electrostatic repulsion decreases and so ADP is more stable than ADP EMP adenine monophosphate is even more stable than adenosine D phosphate because in this case it just have one phosphate grou okay so what I want you to um notice or at least bear in mind at this point in 00:45:49 time is that the hydrolysis of ATP is an energy releasing process and therefore um um is used in the process of anabolism because remember um we mentioned before it anabolic reactions or energy requiring reactions so the energy that um drives I mean the the the energy NE needed or necessary for this anabolic reactions are actually obtained from Mostly from the hydrolysis of ATP if not ATP then GTP okay now this are this is a free energies of hydrolysis of selected Organo phosphates right we also call 00:46:32 them we also call them phosphate transfer potential okay those which have more negative falate transfer potential in other words those which have more negative Delta G not prime or the free energies of hydrolysis have more energy right you know or releases more energy upon hydrolysis for example fosol it releases negative releases 61.9 KJ of energy per mole when it is hydrolyzed compare that to glycerol 3 phosphorate which releases only 9.7 k for Mo okay now that is very important because remember as I mentioned before 00:47:18 you can couple an energy requiring process to an energy releasing process in order to make the process the overall reaction spontaneous so in this case in this case you can um for example couple the hydrolysis of ATP to ADP you're coupling the hydrolysis of ATP with a phosphorilation you're coupling it with the phosphorilation of of uh let's see of glycerol okay why why is that the case because look at that look at that ATP in becoming ADP releases 30.5 remember it's 30.5 right kilj per mole what about glycerol fre phosphate 00:48:11 how much does it need how much energy does it release when it hydrolyzes it releases 9.7 kilog per mole but remember that's for the hydrolysis if you want to cize in other words if you want the opposite reaction to happen that is glycerol plus phosphate becoming glycerol free phosphate and water then that process requires 9.7 9.7 K per mole of energy right if you hydr ATP to ADP you produce one inorganic phosphate and one then isine D phosphate and it relases 30.5 K per mole of energy right instead of 00:49:03 wasting the energy that comes from such hydrolysis what if you couple that with the phosphorilation of glycerol into glycerol fre phosphate is that possible yes because that process in which ATP let me try to write that down hopefully this will work now ATP all right a sorry this is very slow ATP uhhuh plus I'm just going to write G um meaning L what's happening that's G okay glycerol becoming ADP uhuh I'm so sorry this is a DP I have a ter hand writing plus this is I'm going to write G I'm going to Dash p meaning 00:50:10 glycerol three phosphate so ATP let me use my pointer again so ATP is hydrolized to ADP and inorganic falate releasing um 30.5 K per mole right what if you don't let it um hydroly what if instead of doing that you transfer the phosphate Coupe from ATP to glycerol in the process forming glycerol phosphate and adenosine diphosphate well ATP becoming ADP that's already um the reaction that you want it releases -3.5 so that's um 30.5 so I'm going to write that down3 [Music].53 five if you're wondering why my 00:51:09 handwriting is terrible because I'm not using I'm not using um what do you call that a pen here um I'm just using my cursor my handwriting is not that terrible plus okay should it be plus negative 9.7 or plus positive 9.7 it should be plus positive 9.7 right because you're not hydrolized glycerol three phosphate in this case you're actually forming glycerol three phosphate from glycerol so should be it's the opposite so plus 9.7 and notice that the value that you're going to get here is positive I 00:51:54 mean negative so that means that the overall reaction is negative so this means that you coupled the hydrolysis of ATP with the phosphorilation of glycerol to glycerol free phosphate and therefore you're able to synthesize glycerol free phosphate from ATP and glycerol notice that you can ciz um can cize um notice that you can cize um notice that you can synthesize um the uh the uh substances with lower free energies of hydrolysis from substances with Higher free energies I mean when I say higher I mean more 00:52:49 negative free energies of hydrolysis all right okay okay so as you can see here the um the uh as uh as you can see here the uh um the interplay between catabolism and anabolism is clearly shown in this diagr so we have the oxidation of nutrients such as glucose the presence of oxygen Pro is producing carbon dioxide and water um this releases energy and this energy as I mentioned is captured um and used up in synthesizing ATP from ADP and inorganic phosphate ATP is a very unstable substance it hydrolyses in the process of hydrolysis 00:53:48 of ATP to a Denine diphosphate and inorganic phosphate it releases energy that energy is then captured or used by anabolic reactions or endergonic reactions reductive reactions synthesis of um more complicated substances from small precursor molecules okay all right okay in summary hydrolysis of ATP to ADP releases energy and it is this um energy that is typically used or utilized in in powering up anabolic reactions okay in the coupling of biochemical reactions the energy released by one reaction such as ATP 00:54:32 hydrolysis provides energy for another in other words the exergonic reaction makes possible the occurrence of an endergonic reaction the occurrence of a spontaneous reaction makes possible the occurrence of a non-spontaneous reaction in other words a reaction that would not have otherwise occurred if not for being coupled with the more spontaneous for the reaction that is a more negative Delta G okay all right um now a step that is frequently encountered in metabolism is activation now activation this refers to the 00:55:16 formation of a more reactive substance um it it refers to the formation of a more reactive um um substance all right so via process of activation it's like you're priming you're priming the molecule you're first making it more and more unstable before ultimately breaking it apart okay for example look at glucose and we're going to see it we're going to see that later when we study like gsis in the case case of glycolysis if you want to break down glucose as it in its um in its present form glucose is quite stable all right so it 00:56:11 won't undergo cabis or catabolic reactions in its present form what we typically do or however what living systems typically do is to make the um um make the um substance um first more unstable in other words it primes the substance it primes the substance it activates the substance and after after converting that um glucose into a more unstable into a much more unstable chemical species then it suddenly breaks it apart right it's like you're you're you're setting the stage for the catabolic reaction you're activating it 00:57:01 or you're priming the molecule we're going to see that later when study glycolysis so um activation is the formation of a more reactive substance a metabolite is bonded to some of her molecule and the free energy change for making the new Bond is negative right and it essentially causes the um reaction to be um the further reactions subsequent reactions to be exit areon right um for example here you um um you uh this is an example where you activate substance a with coenzyme forming A- coenzyme an example of this 00:57:45 particular class of activation is in the oxidation of fatty acids like you know fatty acids remember fats fats is actually comprised of um glycerol and tri and and fatty acids three molecules of fatty acids remember that call them triy glycerols like your adpost tissues or your fat tissues have a lot of fats um in that case you first hydrolize that process you produce fatty acids and then glycerol all right the fatty acid is then the fatty acid on its own remember you remember the the structure of fatty 00:58:22 acids you have a hydrocarbon chain and you have a CO that substance is extremely stable even if you want to oxidize that it won't happen because that structure is stable so what you do or what the living system does is it reacts the it converts the carox carboxilic acid group into a more reactive species in this case a thioester like coenzyme in that case you have coenzyme a so coenzyme a reacts with the fatty acid in the process producing what they call fatty ail COA and this fatty ail COA is then more amenable to catabolic 00:59:01 reactions and again do not worry about that because we're going to study the details of of of beta oxidation we call that beta oxidation in future discussions so this is just an example where you have a coenzyme activating substance a to produce a more unstable substance that is then um that is that then under goes um a reaction like with another substance substance B producing ab and reproducing the coenzyme all right the coenzymes are ultimately reproduced and regenerated the end of a reaction the end of the 00:59:37 process okay now here is what I was referring to a while ago coenzyme a all right co-enzyme a CO a this is a th group remember I mentioned Fester it is a file group all right it contains units of two mer capto ethylamine look at that this is um mercapto ethylamine where's that mercapto ethyl amine mer capto this one sulfur and ethyl because that's ch2 ch2 and then you have an amine NH right you have panopen acid all right this is this part is penic acid penic acid and you have here again the um adding again the 01:00:31 nucleotide right the the nucleotide so the co-enzyme a all right let me see okay the metabolic I think this is what I was talking about a while ago the um metabolically active form of a carboxilic acid like I have mentioned this a while ago right the fatty acid is the corresponding acil COA Fester all right in which the Fester linkage I mentioned the Fester a while ago is a high energy Bond like uh for example here here is the carboxilic acid right the acetate and this acetate is then um reacted with um this is first 01:01:23 converted into carboxilic acid like um acetic acid it reacts with the coenzyme a look at that look at my um pointer you have HS and o co you for Ayer linkage that linkage is high energy linkage all right so this substance can then undergo reactions with other substances in an exergonic fashion right okay now the catabolic reac reactions are definitely oxidation reactions as I mentioned like before the nutrients or glucoses an example fatty acids the the carbon framework of amino acids these are 01:02:13 oxidized ultimately to carbon dioxide if the oxidation is complete and this process of catabolism actually forms what we call reducing equivalence like nadh and this reducing equ equence are ultimately all right ultimately um oxidized in the electron transfer chain in the mitochondria a process producing ATP like an oxidative phosphorilation again do not worry about that we're going to study that in the future what I'm trying to say is that the oxidation is coupled with the production of ATP all 01:02:53 right so for example nutrients such as glucose V are oxidized and enters the glycolytic paffin and the citric acid cycle um or the kreb cycle and then you produce this reducing equivalent nadh and this nadh now this reducing equivalent are ultimately used up in the process of oxidative phosphorilation oxidative phosphorilation where ATP is synthesized from ADP o we call it oxidative phosphorilation because it requires the presence of oxygen okay all right now then the ATP that is used here is then U rather that 01:03:39 is formed here is then used in anabolic reactions in anabolic reactions and something that I have to mention notice that in catabolism the uh the um form of a nicotinamide add in dinucleotide which is employed is NAD Plus right or produce nadh from NAD plus but in anabolic reactions what you um use is not n a but the phosphorated counterpart like nicotinamide addine dinucleotide phosphate right that's what you use in anabolic reactions okay all right all right so in summary the metabolic pathways were seed in many St 01:04:26 stages as you have seen a while ago allowing for efficient use of energy and you're going to see that later when study glycolysis many co-enzymes particularly co-enzyme a play a crucial role in metabolism right so um this card that's the um um introduction to uh metabolism now okay now we turn our attention to the process of glycolysis now glycolysis is at the center of the I'm not going to say maybe I should not use the term Center but it's it's the entry point perhaps that's the more um accurate 01:05:12 description it's the entry point for glucose into in in the process of metabolism the process of catabolism um glucose is oxidized to two molecules of pyrovate or pyic acid whatever um you want to call it pyoid or pyic acid of course pyic acid is deproteinated into pyoid okay the process of glycolysis is very important as um as I've mentioned it's the entry point of glucose into the U metabolic metabolic pathway okay specifically it's a catabolic reaction catabolic pathway that is geared whose sole purpose is the is the 01:06:00 harnessing of energy from glucose now glycolysis however is not a complete um a complete a com or is unable to harness the energy from glucose completely because in that case in the case of glycolysis glucose is just oxidized into pyic acid or pyoid pyic acid or pyit is a three carbon organic molecule you're going to remember what did we say about the complete oxidation of glucose it must be oxidized to carbon dioxide right the oxidation of complete oxidation of glucose um involves not just glycolysis 01:06:51 right but also the crab cycle right the CB cycle as well as well if you're going to count the oxidation of reducing equivalent the electron transfer chain right for now we're going to focus our attention on the process of glycolysis in the coming meetings we're going to study the KB cycle as well the electron transfer chain and other um catabolic reactions and anabolic reactions involving carbohydrates such as glucose okay now glycolysis or glycolysis gly polies naturally refers to the breakage of 01:07:30 molecules of carbohydrates specifically glucose this is actually the um first reaction first metabolic reaction that has been elucidated and I'm not sure but maybe in biology courses you refer to this as the mden mden mayor Hof halfway in honor of course the discoverers okay now as I've mentioned glycolysis is the first stage in the process of glucose metabolism where when we in one molecule of glucose is first converted to fructose one 16 Bas phosphate which give rise to two molecules of pyate it plays a key role in the way 01:08:23 organisms extract energy from nutrients and one pyro is formed this is very very intriguing very important um it has one of several FES right okay let us first consider the process of glycolysis okay now this is glycolysis from glucose to pyro so this this part of the figure is glycolysis so I've mentioned the pyd can I be um taken up in the citric acid cycle or in the KB cycle and afterwards um the reducing equivalence formed oxidized in the electron transfer chain the process forming ATP in the process 01:09:11 of oxidative phosphorilation that will happen if oxygen or O2 is present in the system is present in the in the organism right in other words you have aerobic oxidation if however um the um the organism that we're talking about does not have a mitochondria if the organism that we're talking about is an ano um then in that case the pyate is metabolized into some other forms okay like um for ex not it does not necessarily refer to an organism it may be a cell a cell of the body I'm not sure if you're familiar with that but um 01:09:56 the um red blood cells the red blood cells primarily um cize ATP by substrate level phosphorilation in other words via glycolysis and glycolysis mostly biog glycolysis alone it cannot perform citric acid cycle because it does not have a mitochondria all right um so what is the term ter for red blood cells in biology aryes the aryes right or you can also have if for example if you're familiar with yeast fermentation of alcohol formation of alcohol from um um pyit pyit pyit is a um decarbox into acet alide which is then reduced into 01:10:52 ethanol we're going to consider each of these in great detail so to not to not be alarmed okay now here is the uh process of glycolysis in a previous figure you see glucose being converted into fructose one six B phosphate and then being converted into two molecules of hyro the process you consume two molecules of ATP but in the end you form four molecules of ATP giving rise to what net formation of two molecules of ADP for every one glucose molecule consumed and the formation of two molecules of n ADH right okay but 01:11:35 that is a very general and a very um bird's eye it's it's a bird's eye view what's actually happening in glycolysis if you want to go to the details and that's exactly what we're going to do now we're going to look at each of the reactions of glycolisis okay glucose until it becomes converted into pyate okay afterwards you're going to consider the Fate in the their fate in the tricarboxylic acid cycle or the crab cycle the anerobic anerobic glycolysis and the um um another anerobic uh glycolysis which corresponds to 01:12:12 alcoholic fermentation now the first step here first step is the phosphorilation of glucose into glucose 6 phosphate that is the first priming reaction what do me you've heard me mention the word prime before right a while ago when I said um molecules or rather the living systems first tend to prime prime relatively stable molecules into becoming more unstable intermediates and this is um I we' mentioned that in like in in connection with the with with the term activation right this is exactly the 01:12:56 same in the first priming reaction you're converting glucose into a more unstable molecule because glucose as I've mentioned is quite stable yes there is a lot of energy in glucose but you have to find a way or the living system must must find a way of converting that or harnessing that energy stored in the chemical bonds of glucose into a form in in into a form which will Rend it um susceptible to decomposition and therefore formation of ATP right and ironically the cell does that by using up ATP right it is remarkable what 01:13:40 happens is that glucose is first converted into glucose 6 phosphate glucose is converted into glucose 6 phosphate in the process consuming adenosine triphosphate okay okay now first and foremost what's actually happening here say for example after you eat after you eat um for example dinner okay so the um after you eat dinner what happens you have this Alpha amasis eat rice for example or spaghetti or noodles um this have starch and this starch or it hydrolized or digested with the alpha analy into Mon maltose and actually to 01:14:27 glucose and then ultimately it will reach the intestines which is where the Moses are further hydrolized into glucose and then what it will be absorbed um uh by the uh epithelial cells in the in the intestines and then transported or unloaded into the blood stream right so your blood immediately after you take up after you eat um after lunch or after breakfast or after dinner your blood has a high glucose concentration right and the function of the erthrocytes of course or the red blood cells is to distribute this 01:15:10 molecules into the different tissues okay like muscle cells like skeletal muscle cells um heart cells um what else liver cells okay hepatocytes now the case of the liver what happened is that okay imagine you for example you're a muscle cell and the blood areright um are delivering your share of glucose what's going to happen is that glucose is going to be transported across your cell membrane across your cell membrane but how is that going to happen how is that going to happen if you remember in 01:15:49 our study of um I think when we studied lipids in the cell membranes we studied facilitated um transport or facilitated diffusion do you still remember that there actually glucose transporter proteins glucose transporter proteins in the cell membrane that binds the glucose delivered um through the bloodstream binds to that and then um unloads it into the interior of the cell okay so there are such there are such um we call them glucose f Transporters or glute glut glute one glute two these are codes 01:16:31 for this glucose Transporters and this is an example of a facilitated diffusion where you have facilitated because you have a protein molecule that assists in the translocation of the molecules of glucose from from outside the cell into the cell but it is still diffusion because the molecules are moving from a region of high concentration to a region of low concentration all right there's also another method another means and it's called um um it it it's coupled to the transport of sodium and I believe this 01:17:08 happens in um I'm trying to remember I think it happens in the renal cells like the cells of the uh cells of the uh kidneys where the transport of glucose is actually linked to a transport of sodium ions this is an example of a sort sort because uh both um sodium and glucose are transported into the cell okay all right so that's I I I share that with you because uh you might be wondering how does glucose enter or how how does glucose enter happen to find itself inside the cell okay by the way VAR reactions of 01:17:53 glycolysis occur in the sight of the PLM right occur in the cytoplasm so here are varac of glycolysis first the phosphorilation of glucose to give glucose six phosphate and the isomerization of glucose 6 phosphate to give fructose 6 phosphate afterwards the phosphorilation of fructose 6 phosphate to yield fructose one six B phosphate notice that this reaction is the second priming reaction right you already used up one ATP in converting glucose to glucose 6 f in this third step we used the second used up a second molecule of 01:18:29 ATP in converting fructose 6 phosphate into fructose 16 Beast phosphate right and this is the next step you've already made it unstable and so what happens is you cleave it afterwards the cleavage of fructose one six B phosphate to give glycer alide 3 phosphate and dihydroxy acetone phosphate afterwards do not worry we're going to study each of these in detail then afterwards isomerization of dihydroxy acetone phosphate to give glycal deide three phosphate okay um there very are numberers so afterwards 01:19:05 is the oxidation of glyceride three phosphate to give one three dis phosphoglycerate and then the um transfer of a phosphate from one three based phosphoglycerate to ADP forming the first molecule of ATP right in the first two in in the succeeding in the previous reactions we're actually using a ATP in this time we're actually forming ATP right in this case transfer to phosphate group from one three B phosphoglycerate to ATP to give fre phosphoglycerate afterward the isomerization of fre phosphoglycerate to 01:19:37 give two phosphoglycerate and the dehydration of two phosphoglycerate to give phospho enol pyro and then a transfer phosphate group from phosph enol pyro to ATP to give pyro then in that case you form the second molecule of ATP but you're you're going to learn later that you're actually forming a total of four ATP in this case or ATP molecules okay so I mentioned do not um not worry we're going to study them in detail so here they are in step one of glycolysis in the first step glucose and see here it is the molecule of glucose 01:20:11 is phosphorilated to give glucose 6 phosphate notice that the enzyme that catalyzes that is called hexokinase right heyas and you have here ATP molecule a den in phosphate and the magnesium mg2 plus right mg2 plus okay now the uh um let me ask you a question why do you think magnesium is necessary previous reaction well hexokinase is the enzyme so it catalyzes the reaction ATP is the source of the phosphate group that phosphor relates this carbon number six see it here right but what is the use of 01:20:54 the magnesium mg2 plus you'll remember that we've already mentioned that before a Denine triphosphate is a very unstable molecule because it has three phosphate groups and you have a net four net of four negative charges right magnesium 2+ actually interacts with the phosphate the negativ the negative charges in the phosphate group positive mg2 plus neutralizing the negatively charged phosphate groups right in the process what lower the energy of a dening triphosphate lower the energy of a densing tri foser 01:21:36 right because it's it's too unstable okay all right so the first step as I've mentioned is the phosphorilation of glucose into glucose 6 fos this is the first priming reaction right notice that in this case you're actually investing energy because you're using up ATP you're not reducing ATP here you're using up ATP okay now the second step is the isomerization of glucose 6 phosphate to fructose 6 phosphate look at that this is glucose 6 phosphate and then catalyzed with the enzyme glucose phosphate 01:22:10 isomerase um the glucose 6 phosphate is converted into fructose um six phosphate see glucose 6 phosphate fructose 6 phosphate okay I hope that is clear this is nothing but isomerization right remember glucose and fructose are isomer these are um structural isomers okay now the fructose 6 phosphate in the third step is then phosphorilated to generate fructose one six Bas phosphate this is the second primary reaction what you notice this is the second reaction that consumes a Denine triphosphate so how 01:22:51 many molecules of ATP have you consumed so far you've consumed two molecules of adenosine triphosphate right for every one molecule of glucose and what is the purpose of this by vist reaction is catalyzed by phosphofructokinase phosphofructokinase actually to be more specific it's catalyzed by phosphor fructokinase one because it phosphates um carbon number one oh by the way I'm not sure if you've already noticed that those enzymes that phosphates molecules are called kinases kinases so hexokinase 01:23:31 phosphofructokinase right phosphofructokinase one in this case because there's fos fructokinase 2 the process it forms not fructose 1 six base phosphate but fructose 26 base phosphate now we're going to learn more about fructose 26 base phosphate when we study the regulation how the regulation of um the in the the metabol the of the a regulation of the metabolic pathways right um for now we're going we're just discussing the reactions themselves okay what can you say about this molecule fructose 6 phosphate and fructose Six B 01:24:09 phosphate which do you think is more unstable it has to be fructose 16 B phosphate right because you have one phosphate group and two phosphate groups remember they are both negatively charged -2 -2 and they are quite close to each other so that makes fructose six Bas phosphate very unstable so I've told you before these are priming reactions they essentially activating glucose into becoming a more unstable substance so that in the end you can break it up you can hydrolize it you can oxidize it and 01:24:43 harness energy harness its energy in the process right okay okay this is or the first three reactions that we've seen the phosphorilation of glucose into glucose 6 phosphate the isomerization of glucose 6 phosphate to fructose 6 phosphate and the phosphorilation of fructose 6 phosphate to fructose 6 F phosphate this are called the energy or this make up the energy investment phase of glycolysis wherein you do not um get any ATP but you actually instead you actually consume ATP right now foros of fluocin is actually a 01:25:25 tetramer all right it exists as a tetramer and subject to allothetic feedback inhibition um remember allosteric side is the site in the enzyme that is not the active side and where allosteric molecules bind or where molecules bind either to enhance the activity of the enzyme or to diminish the activity of the enzyme this is an althetic feedback this is subjected to althetic feedback inhibition um because well as a matter of fact it a Denine triphosphate see here ATP is an allothetic um effector high levels 01:26:04 inhibit the enzyme while low levels activate it so high levels of ATP inhibits for of fruy one do you think that makes sense what is the purpose of glycolysis the purpose of glycolysis is to produce ATP right in the end you're going to see that it actually forms two molecules of ATP all right so do you need to um do you have any need for glycolysis if you already have a lot of ATP no right the cell Will Not Waste its time its effort and its resources and trying to synthesize molecules that it already has in 01:26:46 abundance if you already have ATP and the goal in the process of glycolysis is to produce more ATP then what's the purpose of of of of uh of uh undergoing glycolysis so what happen is that ATP acts as an allothetic inhibitor it binds to the F of fructokinase there's a lot of ATP then that molecules of ATP will bind the for of fructokinase in the process inhibiting this reaction and it makes sense you will inhibit you effectively shut down or at least lower maybe not shut down but lower significantly 01:27:30 diminish the rate of this reaction because you want you don't want any more ATP you already have a lot of ATP so it just makes sense that ATP is an alisic inhibitor of force of fruy one okay fructose one6 BOS this phosphate is also an alisic effector it's an alisic inhibitor it's a feedback inhibitor why because if you already have lots of this this then that means that what you have a lot of what you have a lot of molecules from which to synthesize ATP in the end if you're going to continue producing more and 01:28:08 more fructose one six Bas fite you will have a lot of ATP which you which you do not need right the cell will never will never cize something that it does not need it will only generate something intermediates molecules reducing equivalence that it needs for its normal operation okay so if you already have a lot of fructose Six B phosphate it makes sense that um this reaction will also be um shut down or at least diminished in rate by the product fructose Six B fos as I've mentioned the fos of fructokinase exists as a tetr 01:28:47 subject to alisic feedback a Teter is consist of or consists of L and M subunits all right see here it's actually a combination it must be four but it can be M4 can be L4 or a combination M3 L M2 L2 ml3 and we all we call them isozymes remember when we study enzymes um enzymes exist as isozymes and the isozymes essentially are essentially are I'm not going to say the same but they are they are are what do you call they are different versions of one and the same thing yeah that's how to describe 01:29:30 them there are different versions of one and the same thing for example muscles are rich in M4 while the liver is rich in L4 like m stands for muscle and L stands for liver all right okay um these are a heterogeneous forms the heterogeneous isosym of falto one deser a homogeneous is isos signs of force of trypto one all right as I've mentioned a while ago we have discussed the energy investment phase where that's the part of glycolysis where you do not form ATP instead you actually consume ATP now this is the time for um um now 01:30:16 now the time is near for the energy payoff phase okay so what happened is that fructose 16 BAS phosph is split into two three carbon fragments three carbon fragments this reaction is catalyzed by ales all right the side chains of the enzymes of the amino acids and the active sides that are essential to this process are lien as well as C they play key roles in catalysis so fructose 16 B phosphate the enzyme that hydrolyzes it into two molecules one is dihydroxy acetone phosphate the other one is the glycer Al deide three 01:30:55 phosphate it's catalyzed enzyme called aldolase all right alas okay now what happens next is the conversion the conversion of dihydroxy acetone phosphate into glycerol dehy phosphate okay what are this two by the way this two are structural isomers right dihydroxy acetone phosphate and ghy 3 phosphate are structural isomers what happens in the next step is the conversion of a dihydroxy acetone phosphate into dcal deide free phosphate processed um by the enzyme called trios phosphate isomeric now this is important 01:31:41 in step five a dihydroxy acetone phosphate is converted into glycerol dehy 3 phosphate this compounds are as already as you can notice are trioses this reaction is a small positive Delta G um um it's 0.58 kilo calories per mole and what did you say if you have a positive Delta G then the reaction should not happen right but remember that the process of glycolysis is consist of of many different steps and when you consider when you sum all of the steps in glycolysis you get a net negative net negative Delta G meaning 01:32:21 again consistent with what we have been saying while ago the um spontaneous reactions Drive the non-spontaneous reactions in the forward direction right you understand that so remember that glycolysis as several reactions that have very negative Delta G values and this um this um reaction to very negative G negative Delta G values are the ones that dve reactions to completion so that the overall process is negative so even though this is this is a slightly positive Delta G it's okay because subsequent reactions even the 01:33:00 subsequent reactions and the overall glycolytic reaction has a net negative delta T right okay so in summary in the first stages of glycolysis glucose is converted to two molecules of glycer alide three phosphate the key intermediate in the series of reactions is fructose 6 this phosphate enzyme that catalyzes this reaction is FAL of fructokinase and it is subject to allostatic control okay now those reactions consist the um energy investment phase right up to this point you still haven't encountered en any any 01:33:40 reaction that produces ATP right no nothing yet by the way fructose one6 Bas phosphate the formation of fructose 16 Bas phosphate this reaction is called the committed step in glycolysis why why do you call it committed step what does it mean when you say it's committed to that H when you say it's committed that means what well you should know this um um committed comes from the word commitment right when we say that this is the committed step in glycolysis that means that once fructose 6 phosphate is 01:34:31 converted into fructose one six bis phosphate it has no other choice but to undergo glycolysis to the finish right to the finish up to fructose 6 phosphate it's still okay there are still a number of choices available for it fructose 6 phosphate can be used in glucal Genesis it can it can be um um uh what do you call it can be U funneled to other metabolic pathways but fructose 16 Bas phosphate is is found or is does not participate in any other metabolic pathways it participates or it is involved only in glycolysis so that once 01:35:19 fructose 16 Bas falate is formed but fructose six BAS falate cannot undergo any other reaction but to undergo cleavage into dihydroxy acetone phosphate into the be theide 3 phosphate and then complete the steps to pyate that's why it's called the committed step right okay commitment committed step all right okay now this is the I believe this is the payoff phe bhide three phosphate is converted to py the first reaction but Begins the conversion to pyro it involves the oxidation of glycer dehy 3 01:35:59 phosphate this glycer dehy 3 phosphate excuse me to one free bis phosphoglycerate now before anything else let me ask you a question how many how many glycer deide three phosphate do we now have we have two right so you're going to ask me sir why do we have two remember we when we CLE fructose 16 B phosphate we ended up with thisal deide 3 phosphate as well as Di hydroxy acetone phosphate right but the dihydroxy acetone phosphate is converted into another molecule of of of glyceride 3 phosphat so in the end you end up with 01:36:36 two molecules of glycer alide three phosphate right okay so all of reactions that we're going to encounter now will be times two because we have two molecules of glyceride 3 phosphate so glycer alhy 3 phosphate is oxidized by NAD plus rather um is oxidized yes um by NAD plus um using glycerol deide three phosphate dehydrogenase as a as a catalyst as an as the enzyme Catalyst you produce one three this phosphoglycerate notice that this is the first time that you encounter NAD plus right NAD plus is converted into 01:37:22 nadh and that is very important we're going to go back to that later but that is very important okay now the oxidation of glyc alide fre phosphate is um an ener an energy releasing reaction look at that um I'm I'm trying to tell you this because this step actually consists of two steps right the oxidation of glycerol deide fate into um into um threee phosphoglyceric acid and the phosphorilation of phosphoglyceric acid to u to one three Bas phosphoglycerate okay in other words it consists of these 01:38:06 two steps first is the oxidation of glyceride three phosphate the second is the um formation of what is this this is not an eser this is an anhydride C phosphoric um car boxylic anhydride this is a phosphoric carboxilic anhydride all right so you see that this reaction actually consists of this two reactions and the first reaction has a negative 10.3 kilo calorie per mole Delta G Prime the second reaction has um um Delta G Prime of 11.8 okay of 11.8 notice that there is a net there is a net slightly positive 01:39:00 slightly positive Delta G not prime but then again it doesn't matter because the overall reaction of glycolysis is negative that the the subsequent steps in um after this are very exergon okay now what happens actually here is that the um th group of the cine resue in the enzyme active side rea with the um um alide in the process produces intermediate afterwards this um um alcohol group is oxidized the hydride is transferred from the um three phosphoglycerate rather threee glycer alide three phosphate or there is 01:39:45 actually um I'm not sure if you remember that but this is um a Hemi uh I'm not sure if you remember that in organic chemistry hopefully you do if you replace this of an what is that that's um an aceto right that's a tho since that the sulfur they call that um AO acetol all right a um acetol okay that Pho acetol is oxidized and the hydride is transferred to na Plus producing NAD all right and what happens here is that this thioester this thioester is reactive because the sulfide leing group is a 01:40:35 good leing group so that um that inorganic phosphate attacks that and ultimately the U carbon sulfur bond is broken and you end up with one three base FAL for the okay now here oh before anything else notice the source of the phosphorus rather the phosphate the source of the phosphate group here is not ATP but inorganic phosphate inorganic phosphate right inorganic fos now in The Next Step this is the very interesting one because this is the first energy producing orever ATP producing reaction in glycolysis this 01:41:19 step involves another reaction in which ATP is produced by phosphorilation of ATP all right this reaction is called the substrate level phosphidation what happens is that ADP right reacts with this molecule this phosphate group is transferred to ADP producing ATP and this is three phosphoglycerate this is the first reaction where we encounter the formation of ATP and this is called substrate level phosphorilation um to differentiate it or to contrast it with oxidative phosphorilation okay so you produce one ATP here now three 01:42:00 phosphoglycerate this one three phosphoglycerate is isomerized to two phosphoglycerate with the enzyme phosphoglyceromutase so three phosphoglycerate is converted into two phosphoglycerate okay and this is where it gets excited because afterwards an enzyme called enolase will cause the elimination of a molecule of water again this is something that you've learned in organic chemistry the elimination of a molecular of water going to end up with this substance you have a double bond here this is called phosphoenol pyro and 01:42:36 phosphoenol pyit is a very important intermediate why because the fosho enol pyate then reacts with ADP to produce pyate and ATP that's where the second molecule of ATP is produced okay now before anything else I'm not sure if I discuss that okay here notice that phosphor enol py of it transfers its phosphate group to ADP producing ATP and Pyro notice that the phosphate transfer potential we've mentioned that before in our discussion in the introductory part of our discussion and um we also call 01:43:15 that the Delta G of hydrolysis in this case of Delta G of hydrolysis or the phosphate transfer potential of phosph inol pyit is more is higher back of ATP 61.9 as opposed to 30.5 K per mole so definitely ATP can be cized from ATP and phosph enal pyate okay okay this is the second second um reaction in ATP in the energy payoff phase of of of glycolysis where you generate ATP the question is how many actually how many do we have how many ATP molecules do we produce here um it's not that it's not that big but hopefully you can see that 01:44:07 so this is the phase one all right that's the phase one or the energy inv investment phase from the first second third fourth and uh first second third fourth and fifth a fifth reaction that's the energy investment phase this is phase two the energy payoff phase um where you produce um ATP so in total how many atps do we actually form remember he used up two molecules of ATP in the energy investment phase in the energy payoff phase he produced two molecules of ATP per molecule of glycerol dehy 3 01:44:47 phosphate right but how many glycerol dehy three phosphate do we have we have two because the other dihydroxy acetone phosphate is converted into glycerol dehy phosphate so effectively we have four molecules of ATP right four molecules of ATP form minus the two molecules of ATP that we have consumed in the energy investment phase that gives you two molecules of ATP see that the ATP yield in glycolysis is actually very poor right it's actually very poor uh just 2 ATP but you know what the erthrocytes 01:45:25 they don't have any other source of they don't um have any other way of of of of um harnessing energy other than glycolysis anerobic glycolysis because they do not have mitochondria okay so this is the only way for them to harness energy okay and what else this also tells us but how many molecules of nadh did we form we form one from here and one from there remember a while ago I told you that it's very important to zero in on such reaction why you know what the problem is that what happens say for example if 01:46:05 NAD plus is consumed what happens if NAD plus is consume happens this reaction can no longer occur right and just imagine that you do not have an unlimited supply of NAD plus and nadh you're actually risk recycling this molecule it's not it's not like glucose that you actually take in right it's it's a metabolite that is present in your cell in limited quantity in other words N plus will after some time become depleted and if that becomes depleted then this glycolytic pathway will have to stop all right how did the 01:46:53 cell regenerate any DH we're going to learn that later okay from now let's go back to this what are the control points in glycolysis when you say control points these are the points that we either inhibit or re activate further in order to produce more ATP or to lower the amount of ATP like because it responds to similar like if you already have a lot of ATP then what's the point in synthesizing more ATP you will have to shut down or at least slow down this pathway right because you do not want to 01:47:29 waste energy and resources while if you're desperate if you're energetically deprived then the cell will have to cize ATP and this pathway has to be activated so what are the control points or the regulatory points in glycolysis free reactions exhibit particularly large decreases in free energy and these are this reactions are the are the reactions catalyzed of enzymes hexokinase FAL fructokinase and Pyro this the first step this the committed step and this one the last step notice that metabolic pathways are 01:48:06 typically controlled either at the beginning at the end or at very um as you can see in this case um reactions that have very um that are very exergonic that have very negative Delta G you know what we're going to study more on what are the factors what are the factors that um affect or that regulate the glycolysis in detail in subsequent meetings why because I want to discuss integration and regulation of metabolism as a whole not not piece not piece meal or piecewise like because we're going to 01:48:53 study crab cycle we're going to study glycogenolysis we're going to study F we're going to study pentos phosphate path we're going to study gluconeogenesis glycogenolysis lipolysis and so on so forth so I want I want you to learn how all of these are related to each other and are controlled um by metabolizes and by the cell um um as a as a whole okay you're going to you're going to appreciate its Elegance more that way for now I just want to emphasize that the control points in glycolysis are reactions catalyzed by 01:49:30 hexokinase phos fructokinase the pyin well actually in fact you've already discussed some aspects of control like when we said that um fructose one6 bis phosphate inhibits is a feedback inhibitor of fos fruin one right ATP is also an alisic inhibitor of fos focas one you know what we're going to study more we're going to learn more about that in in the future okay now the going back to the question that I post that that I posited a while ago what happens to any D+ like if if the reaction continues to go on and on 01:50:10 without you regenerating n D+ then you're going to run out of NAD plus right and their process is going to shut down and you do not want that to happen especially if you're a red blood cell where you don't have any other source of energy so what happens is that um in the absence in the absence of a sorry as I mentioned a while ago we're going to encounter a problem if nad+ becomes depleted right so the cell must figure out a way of regenerating regenerating n A+ okay no um okay I'm looking [Music] 01:51:04 for I'm looking for a bad pathway show you this okay here now if you have oxygen all right if if you're if you're talking about an aerobic organism like ourselves we're we're aerobic organisms right or if you if you have an aerobic organism and that organism has uh is faced with sufficient supply of oxygen then the n h as you can see here the nadh that is produced from glycolysis and in fact the nadh is produced from the citric acid cycle as well will simply be oxidized all right will simply be 01:51:50 oxidized back into n plus and that this process is called oxidative phosphorilation because it is coupled to the formation of a dening triphosphate um now this allows the Regeneration of nad+ and that NAD plus is again used upop here in the process of glycolysis and even in some other aspects of the citrica cycle um reactions which we going to study next meeting um so there's no problem if you're an aerobic organism with um we with uh lots of oxygen in your environment right you know the problem is even if 01:52:33 you're an anerobic even if you're an aerobic organism such as us humans problem is what if you were you're doing a strenuous exercise like consider your muscle cells during a strenuous exercise for those of you go to the gym for examp example um those who are doing exercises or even at home those who they're doing exercises at home um you experience this sometimes you um feel cramps I mean you experience cramps right cramps result from the accumulation of lactic acid okay and this typically happens to muscles that 01:53:19 are undergoing vigorous exercise in other words undergoing vigorous exercise um so much so that that not enough not enough oxygen is delivered to their muscles all right not enough oxygen is delivered to their muscles and the problem with that is as follows when you when you um um two strenuous exercise not enough oxygen is delivered to your muscle so you cannot do this you cannot proceed P ofid cannot be oxidized into acet Co and proceed to the citric acid cycle and oxidative phosphorilation this cannot 01:54:04 happen because there's no Oxygen see that oxygen is needed for this process aerobic oxidation so you don't have any choice but to do anerobic glycolysis and in anerobic glycolysis p ofate is converted to lactate okay now let me show you VAR action in that case here that case P of it that is produced some glycolysis will be reduced by nadh into lactate or into lactic acid all right and notice that this reaction regenerates the nad+ this ensures that you're able to continue um uh that you're able to provide energy in 01:54:55 the form of ADP for V for your exercise or for whatever muscular activity it is that you're engaged in okay the problem is you encounter a buildup of lactate right this is quite problematic because typically when you have a buildup of lactate in muscles you experience cramps all right and I'm not sure if you if you're if you have ever experienced that but have you um I don't know how to describe it um say for example when you're sitting crossle cross-legged um when you're when when you put one of 01:55:40 your legs on top of the other for example right and you're doing that for quite a long time or for quite sometime what happens to the leg underneath it it doesn't feel I think it doesn't feel well right it's um you um experience cramps or cramping that's because in doing so oxygen is not delivered to that part of your body and so the cells do not have any choice but to undergo anerobic glycolysis in the process produce lactic and it is lactate that causes cramps okay right so what's going to happen the lactate 01:56:33 fortunately that is formed is actually um delivered via the bloodstream to the liver and the liver then reoxidizes lactate back to pyate and the P of it that is formed in the liver is either used in the crab cycle or used in the process called gluc neogenesis but is the cesis of glucose from Pate all right um we're going to study that in the future glucon neogenesis but let's focus more let's focus now on the anerobic metabolism so that's what happens right um this is what happens in anerobic gcis this is how NAD plus is 01:57:19 regenerated oxidation of nadh by py okay okay oh this is exactly what I'm talking about right so the uh uhuh where is that the pyate is reduced by nadh into lactate and then the NAD plus that is regenerated is used up in what in oxidizing glycer Al deide free phosphate to one free B phosph glycerate without this reactions without this reaction rather this step will continue will will stop to occur why or will cease to occur why because you've used up all of your nad+ thankfully the oxidation of nadh by 01:58:14 py it regenerates any plus now let's go to the alcoholic fermentation the process produce ethanol okay so the glyceride 3 phosphate it's the same produce one F this phosphoglycerate and then pyro now in alcoholic fermentation what happens is that the pyate undergoes decarbox silation it under goes decarbox silation so this carbon dioxide is released and you produce acetal this acetal deide is the one that oxidizes nadh back into n e+ in the process of letting or making possible theaction to continue to happen and what happens to 01:58:59 acetal deide then acetal dhide is converted into ethanol right acetal deide is converted into ethanol and so you're alcohol like in beers in Liquors and so on so forth that's how you ferment okay now the that converts pyro to acet alide is called pyate decarboxylase and it requires the action of the enzyme thomine pyrophosphate right thyine pyrophosphate actually is there this is thamin phosphate by the way it is derived from the um vitamin B1 all right vitamin B1 F can see the the active the active the 01:59:51 chemically react active species here is the fizor ring specifically this carbon that under goes the protonation to produce a carbon so let's go to the yield let's talk about the yield of ATP how many atps do we form we form two molecules of ATP or one molecule of glucose remember we also produce um well two molecules of NAD but it's ultimately converted back into into Ned Plus in the case of the case of anerobic um anerobic glycolysis right okay but it is different when you when when when pyit is oxidized into acetyl 02:00:46 Co and enters the tricarboxylic acid cycle the oxidative phosphorilation okay fact you're going to learn but you're actually get going to get much much much more ATP when you do um oxidative respiration okay oxidative respiration um or rather aerobic glycolysis okay now I want to say gly pois is exergonic and releases 73.4 K per mole okay I want to emphasize that not all of the energy that is um that is harnessed or not all of the energy that is released from the oxidation of glucose into pyro it is actually harnessed in the form of ATP some of them are what some of them simply are liberated in the form of heat and that heat is used to what warm us to warm us like to maintain body temperature warm blooded organisms such as ourselves okay um we're going to learn more about metabolism in the next meeting where we study the tri carboxilic acid cycle as well as the the process of oxidative um phosphoric um before I dismiss you I want to mention something like I'm not sure if you're aware of that but are you familiar with the fact that some people are allergic to alcohol right some of them simply cannot consume much alcohol some actually cannot consume alcohol at all and this is called an Asian this is called asian flush syndrome Caucasians rarely suffer U from this from this condition because Caucasians they drink a lot a lot of of beer a lot of alcohol they have high tolerance for alcohol um Asians have to low tend to have low tolerance to alcohol but I'm not generalizing of course because you know that because you know that um some some Filipinos are addicted to alcohol not just Filipinos of course some other Asians but of course Ians for example Japanese and some Filipinos of of of Chinese lineages they actually suffer and Japanese lineages suffer from the condition know this Asian Asian uh flush Chap 18 00:00:00 now in today's discussion we're going to consider the the um um other aspects or other path involving the metabolism of carbohydrates specifically the um degradation of glycogen synthis of glycogen as well as the pentos phosphate path and the glucon Neo chesis we also considered control different ways in which we control the um organisms control the metabolism of carbohydrates all right so in the previous discussion we've learned the process of glycolysis we've learn the different steps of glycolysis and the control points GES 00:00:49 today we're going to expound more on what happens to some of the intermediates that have been implicated in glycolysis or they're implicated in glycolysis and also consider some other Pathways relative Pathways more importantly the way with which the organisms regulate the metabolism of carbohydrates all right so first and foremost we consider the substance called glycogen now glycogen is actually very similar in structure to starch we have discussed structure and starch in the past and you've learned that 00:01:33 starch that starch is a branch molecule right glycogen also is a branch molecule in fact the structure of glycogen is such that it's able to maximize the number of glucose recipes that it can that it can store and that the organism can therefore utilize and expand in times of need in fact molecular model mathematical modeling revealed that the structure of starch rather the structure of glycogen which is by the way called animal starch um is such that it holds the maximum amount of glucose that and 00:02:18 therefore of energy for a glucose polymer that can possibly store in times of heat and that the branching actually makes this makes this possible all right so let us ask ourselves a very important question first what happens say for example when you take in carbohydrate Rich meal after meal you have lot of glucose in your in your blood right so what happens exactly so what happens is that during digestion starting from your mouth St amul of course digest be um rice for example or bread carbohydrates 00:03:01 andent Mose and glucose course the substances are this polymers and resolving disaccharides are ultimately digested even more the small intestine they cross the uh intestinal mucose and then go to the blood now the blood then becomes rich in in U glucose after a carbohydrate which so you ask yourselves the question what will the um what do the body do with that um flood of of glucose molecules glucose carbohydrate energy source but we know that um cells will never waste energy will only take in what it needs and it will 00:04:04 not uh take it will not metabolize what it does not need right so if there is a flood of glucose molecules in the blood the tendency is for that glucose molecules to become polymerized and therefore stored in the form that can be mobilized for a future use so that's exactly what happens the liver the liver um ciz is glucose however ciz is glycogen stored for storage form of glucose um from from glucose that's uh found in the blood immediately after carbohydrate Rich all right um muscles can also do that you 00:04:54 know to synthesize gly right now before we consider the synthesis of glycogen let us consider the glycogen likis first or the degradation of glycogen the degradation of glycogen naturally entails the um the uh decomposition of glycogen into glucose and what activities what you can think of that might U entail the degradation of the well what do you think um a starvation say for example if you're not eating anything at all or if you're fasting then your your body will have no choice to metabolize the glycogen storage that 00:05:44 you have in fact is the glycogen stores that are first metabolized um when you are fasting and afterwards your bodying um turn on your fats ultimately when you're run out of fats to turn on your own prot protein or amino acids we're going to study that in the future but not only in cases of fasting or station does one metabolize gly but also during exercise like during intense and strenuous exercise the uh body um tends to utilize glycogen especially the muscles remember we discussed before the U any glycolysis 00:06:38 and you said that during hypox during conditions of anoxia in other words when you're when you're doing a very strenous exercise that you're very intense and strenuous exercise but there's no time for oxygen to be delivered into your muscles so your muscles um will have no other choice but to um to to to um um utilize glucose using anerobic pois because there's no Oxygen present to ultimately oxidize pyro and to the and encourage it to go to the carox active Tri carox gide oxidize the reducing equivalent form there so what 00:07:22 happens is that as we're going to learn the future the TR carboxilic G cycle is shut down so your muscle does not have any choice to metabolize glucose and aerobically through glycolysis the problem with that is that the yield of GIS remember is not an ATP is not that high it's just two ATP molecules for every glucose molecule rabiz so during strenuous exercise or during intense exercise you though your muscle will have to want in order to sustain um muscular activity and to provide enough ATP for your Contracting muscles the 00:08:02 muscle will have no choice but to eat up a lot of glucose and where where does this glucose come from this glucose comes with the breakdown of of um glycogen stores in your muscles right in your muscles right ultimately um this glycogen is lized into not to glucose but to a metaboli of glucose which we're going to learn in a moment and this metaboli of glucose specifically glucose one for is enters the the glycolytic pathway anerobic where leads to the accumulation of lactic acid which causes cramps or 00:08:49 muscular pains during the process of any rubic or when you're doing such strenous exercise all right okay now let us turn your attention to the process of glycogenolysis all right now glycogen lysis is the breakdown of glycogen into component into its components this mentioned glycogen consists of glucose but naturally you're not going to end up with glucose um in Galis instead you're going to end up with glucose one phosphate right and we're going to look at the mechanism of that liis or glycogen liis um pathway in a moment so 00:09:36 let me use my pointer all right glycogen is Cle by phosphate to give Alpha T1 phosphate as you can see here this is glycogen glycogen iming that it's a polymer glucose a highly branched polymer glucose consisting of al4 glyptic linkages as well as alpha6 glyptic linkage the process is not hydrolysis it is phosphorolysis because you're using a phosphate ion in order to Cle glucose forever in order to release glucose one phosphate from the molecule so this phosphate ion attacks the glycogen the process reducing 00:10:19 glucose n minus one other words glycogen plus one less one less glucose molecule and you have glucose one phosph by as the as the product of the of your reaction you release glucose one phosphate now cleavage reaction sub mention is phosphorolysis and not hydrolysis because you're using a phosphate iron instead of water in cleaving the molecule into its component no ATP is involved in this reaction and the reaction is catalyzed of the enzy called gly the later we're going to consider it more study we're 00:11:00 going to have more to say about the properties of the enzy glycogen phosphor right okay so this is the first step in the uh process of glycoanalysis the release of glucose water FAL right but remember what happens is that you you're releasing again during that strenuous activity or intense muscular activity when you're doing a strenuous exercise your your mus so then to undergo any Ro of respiration then they need a lar of glucose molecules this is not a glucose molecules a source of energy now this is not a glucose right 00:11:41 this is glucose rfor remember that's going to be metabolized in glycolysis and how does that enter or how does this metabolite enter the process of glycolysis remember process of glycolysis first step is actually the phosphorilation of glucose into glucose 6 falate right um this is not glucose 6 falate so what's going to happen is that in order for this metabolite to be or the substance of the metabolized gsis it will have to be converted or isomerized to glucose 6 phosphate and that's exactly what happens the second reaction 00:12:19 the glucose one phosphate is asiz to glucose 6 phosphate um by the an phosphor gluc mutat glucos on phosphate is converted into glucose six F right and then this this glucose six F right can then enter the glycolytic pathway process providing the the the um muscle with glucose and you will have to remember the the muscle is licing or his his U his decomposing gets glycogen a very significant traser but you're in order for the muscle to have enough ose to sustain its trous activity in other words you're providing the um muscle 00:13:03 with a lot of glucose molecules in the form of glucose white foser now I want to bear I want you to notice that this reaction does not um entail the consumption of ATP because remember in usual normal GIS glucose is converted into glucose ex phosphate bya what coupled um reaction with ATP or Denis and triphosphate so this case you're bypassing that um that uh um reaction the U energy investment phe so that in fact the the um what do you call that the uh yield quote unquote for glucose molecule ATP yield for 00:13:50 glucose molecules Goen um ATP yeld going those molecules in in glycolysis comes from the glycogen liis of glycogen is actually three right um actually three I mean h h how many how many uh how many ATP molecules do you generate okay um in the case of uh just normal glucose from the blood stream but is um metabolize and GL policies we'll need two molecules of ATP remember um for for the investment phase and then for molecules of are going to perform in the payoff phase so that's going to be a net of two molecules of 00:14:51 ADP in this case you're not um using a you're not effectively um using um two molecules of ATP energy investment pH or just because this is already glucose 6 fate right um so what effectively is that you're bypassing the first phosphination step in glycolysis so you just