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now in today's discussion we're going to consider a citr cycle citr cycle is part of the oxidative um mechanism for the for the um um extraction of of energy in the form of ATP from from glucose and from other from other fuel sources citric acid cycle is intimately associated with the El for chain all right for now we're going to focus our attention on this CC the reactions involved in it its regulation and its Ro in metabolism all right previously we have considered glycolysis and other other other carbohydrate we've learned in we've learned that in glycolysis V the E of ATP is just two molecules of ATP per glucose molecule and we tributed this relatively small gain or yield in ATP to the fact that very reaction the oxidation of glucose to lactate in the anerobic gis um the fact that this process um is incomplete in the sense that the molecule glucose is incompletely oxidized into into um into molecule py of it and ultimately ined you're going to notice the glucose is a six carbon sugar and in the in the oxidation um um py lactate he ended up with just two three carbon sugars and therefore the molecule is not completely op a very small only a very small fraction of energy chemical energy contained in molecular glucose has been extracted in the instant molecule in citric acid cycle molecule of glucose is completely oxidized to carbon dioxide remember carbon dioxide is the most oxidized form of of carbon therefore the conversion of glucose to carbon dioxide entails the complete oxidation of glucose in this Cas okay the the citric acid cycle is a central role in metabolism in fact if you're going to map out the entire entire metabol path you're going to find citric acid cycle be somewhat at the center right the citric acid cycle is a catabolic pathway but is also an anabolic path three process play Central roles in arobic metabolism first is a citric gas cycl second the electron transfer chain and then the oxidative phor we're going to discuss El transf also foration next session for now we going to consider the citric acid cycle now citric acid cycle is also known as the CB site or via tribox site CB cycle the owner of pans SCB who has discovered this pathway um the tri cyle because the fact the V cycle consists of some some compound with three carboxilic a GRS as intermediates the metabolism number consists catabolism the opid breakdown of nutrients and anabolism just a reductive synthesis of bi subvention to it's both a catabolic and um an anabolic pathway in other words it's anti because plays a role in both catabolism and anabolism it this Central metabol all right now this is um diagram of of how exactly we get um ATP from from pyate in the process of oxidative respiration OA respiration the game consists of of a CB cycle the um the electron transfer chain as well as of for let me use my poter all right so first is that remember that py of it or the py of it py it is formed from the oxidation glucose in anerobic glycolysis or should not say anerobic glycolysis I should say in glycolysis anerobic glycolysis remember is when glucose is converted into Latin so um in glycolysis Spate is formed from glucose the glucose um fatty acids Ethan and amino acids um are oxidized into of AET coin like glucose it's oxidized P of it which is then oxidized with a pyro dehydrogen complex it under go decarb oxidation reducing the first carbon dioxide out of P of it um the process converting it into acid over fatty acids also oxidize into acids amino acids they are carbon framework oxidized into acet this acet molecules um enter citric acid cycle so citrate and citrate when that's the intermediate it's not citrate ex but in intermediate under go oxida carb oxidation so here goes your second carbon dioxide molecule out fire the remaining third car remaining third carbon dioxide colum are the third car in IR it um here you lost it here and steps um in in from for production of acet to some of the steps in the C cyle reduce reducing equivalence typically ncle n or flri F A2 and this um nadh and fh2 are oxidized in the electron transfer Shing oxidative phosphidation coupl to oxidative phosphidation the process yielding a Denine Tri phospher to ADP and inorganic phospher what you to bear in mind is that the ultimate elant acceptor in this case is oxygen that's why it's called aerobic respiration right so here are the three important steps in the proc process of oxidative oxidative respiration gain the oxidation of P of it to a the oxidation citric and then the Elon transfer right now where is the citric acid cyle take this it takes place inside the mitochondrion right um process of glycolysis and the process of glucomen um except for some steps glucon Genesis the conversion of pyamid into FAL pyamid that occurs in Mond glycogenesis and glycogenesis um this independ those F pathway this occur in the cyos but um the citr cycle occurs in the mitochondria so it is important for us to um remember or excuse me um consider the structure of the mitochondrion the mitochondrion consists of an inner and an outer membrane right inner and outer membrane the actions in the U cab cycle occur inside the or within the the inner M within the inner membrane and that region in space is called the um mitochondrial Matrix there is one reaction though of citric added cycle does not occur in the Matrix the mitochondria but occurs on the um URS on the um inner mitochondria inner mitochondrial membrane itself because the enzyme that is in form in that reaction is actually an integral membrane okay now molecules can more or less freely penetrate go in and go out of the out mondri membrane but MO but that only certain molecules are able to cross the those specific Rin Transporters um that are that are able to um let them in or let them out of the mitochondrial of the inner mitochondrial membrane the space between the the inner and outer membranes will be um the intermembrane space and the intermembrane space will it's important in in oxidative deoration will be more apparent in our next discussion okay so these are the features ining features of the C cycle gain pitsis is oxidize into acet COA leading to the formation of carbon oide and nadh acetal reacted oy acetate in the process catalyzed by citrate synthase the process producing citrate now citrate is when um isomerized by a conas into isocitrate isocitrate under go um oxidation into Alpha keto glut process forming second carbon dioxide from pyit the first is obtained from the oxidation of pyit a cal the dehydrogen now the alpha ketter is formed then under goes another round of oxidation producing that second carbon dioxide and this one nadh G that's already one two three third n and then this to produce so then is converted so by so synthetics um producing GTP GTP is just um converted into ATP with enzyme nucle nucleo diphosphate K right the subate is when oxidized F so hyrogen fumate now the process producing not not um not n but fadh2 is reducing it is the enzyme that occurs in the inner mondri membrane because assin hydrogenous is an in the fumerate is under is hydrated into malate by fumas and the malate is dehydrogen process one cycle and you for the another molec right we going to consider the details of this reaction now okay P of hydrogenous complex is the enzyme that is responsible for the conversion Pate carbon dioxide and the acid portion of a now SC the complex actually five enzymes that that are found in this complex five enzymes are are um associated with each other right to to produce a complex system now the five enzymes in the complex consist of pyro dehydrogen the hydr trans dihy dehydrogen h dehydrogen in dehydrogenase phosphatase now the last two the cyas and the phosphatase are enzymes that are involved in the regulation of activity of the P de hydrogenous compx first one involves py dehydrogen is needed in the oxidation of acet second is needed for its reaction with acid with with Co a or coenzyme a also given the symbol coash um and then lastly the dihydro the hydrogen is needed for the the oxidation of the liic acid oid okay first hopefully all right there is this diagram the first VES carbon dioxide and hydroxy TPP is4 Second Step was the catalyze of the enzyme of it dehr right the second set the active form of liic acid respond to the enzyme um the hydr trans might to the Epson okay then dehydro group is oxidized and transfer it to sulfur red am and Le am is reduced to hydro step three trans Coen next do not great going to discuss in detail now first step is a loss of carbon dioxide and the formation of hydroxyl TP so as I mentioned this is p it um first molecu carbon dioxide is removed with the process of oxid decarbox silation decarbox naturally because carbon dioxide is removed from the molecule process producing this intermediate hydroxyl DP notice it this part of the molecule is this part now this substance then underg reaction with lipoic acid okay with lipoic acid in the process see forming this intermediate in which sulfur sulfur bond has been okay by the way this first step is is catalyzed by P dehydrogen okay second step is catalyzed by dihydro transet which is the reaction between hydroxy PP and oxid theic acid this one process producing the um acetal Ro where SC conect sulfur that is a high energy bond by is a thester bond right it's D is highly exer going so you have sh the second or the third step is reaction with a coenzyme a or Co now it is Coen a is is a molec that has a f GR in the end that's why it's it's a an analog number files are analog instead of having an S an oh we have um an sh all right we have an sh okay um um then what is the next step The Next Step remember once theen May reacts with this sulfur you end up with trans the process is transes statification because one Fester is replaced by another Fester this is another Fest another high Mo high energy molecule so um in the next step notice that the S carbon bond is replaced by an S1 effectively red