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PYRDEHYDRO - The Aerobic Fate of Pyruvate Bryant Miles I...

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The Aerobic Fate of Pyruvate Bryant Miles I could tell that some of you were not impressed by the mere 2 ATPs produced per glucose by glycolysis. The 2 ATP’s produced are only a small fraction of the potential energy available from glucose. Under anaerobic conditions, animals convert glucose into 2 molecules of lactate. Much of the potential energy of the glucose molecule remains untapped. Under Aerobic conditions a much more dynamic pyruvate metabolism occurs. The 2 moles of NADH produced by glyceraldehyde-3-phosphate dehydrogenase are oxidized in the electron transport chain back to NAD + . The electron transport chain generates a proton gradient that drives the synthesis of 5 ATP molecules from ADP and Pi. Further more, the pyruvate formed by glycolysis is converted to acetyl-CoA by pyruvate dehydrogenase (generating another 2 moles of NADH per glucose and another 5 ATPs by oxidative phosphorylation). The acetyl-CoA formed enters into the citric acid cycle where it is completely oxidized into CO 2 . The electrons liberated by oxidation are captured by NAD + or FAD which are then transferred via the electron transport chain ultimately to O 2 , the final electron acceptor. The electron transport chain is coupled to generating a proton gradient which produces a proton motive force that drives the synthesis of ATP. This allows the net production of 32 molecules of ATP to be formed per glucose molecule. The function of the citric acid cycle is to harvest high energy electrons from carbon fuels. The citric acid cycle is the central metabolic hub of the cell, the gateway of aerobic metabolism. The citric acid cycle produces intermediates which are precursors for fatty acids, amino acids, nucleotide bases, cholesterol and porphoryins. The citric acid cycle is shown on the next page. The citric acid cycle occurs in the mitochondria of eukaryotes. New carbons enter the citric acid cycle through acetyl-CoA. The acetyl group may come from pyruvate, fatty acids, ketobodies, ethanol or alanine. The two carbons of acetyl-CoA are transferred to oxaloacetate to yield the first tricarboxylic acid citrate in a reaction catalyzed by citrate synthase. A dehydration followed by a rehydration rearranges citrate into isocitrate. Two successive decarboxylations coupled to the generation of 2 NADH produce succinyl-CoA. Four steps later oxaloacetate is regenerated along with a GTP, FADH 2 and NADH. The citric acid cycle may seem like an elaborate way to oxidize acetate into carbon dioxide, but there is chemical logic to the cycle. In order to directly oxidize acetate into two molecules of CO 2 a C—C bond must be broken. Under the mild conditions found in cells, there is insufficient energy to break the bond. Biological systems often break C—C bonds between carbon atoms α and β to a carbonyl group. Examples are aldolase and transaldolase.
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