regulationtca - Regulation of the Citric Acid Cycle Bryant...

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Regulation of the Citric Acid Cycle Bryant Miles I. Changes in Free Energy 1.) Citrate Synthase 2.) Aconitase 3.) Isocitrate Dehydrogenase 4.) α -Ketoglutarate Dehydrogenase 5.) Succinyl-CoA Synthetase 6.) Succinate Dehydrogenase 7.) Fumarase 8.) Malate Dehydrogenase 9.) Overall reaction Δ G o Δ G 3 Molecules of NADH and 1 molecule of FADH 2 are generated each turn of the Citric acid cycle. The eight electrons captured are transported by electron carriers to O 2 generating a proton gradient that drives the oxidative phosphorylation of ADP to generate ATP. The stoichiometry of electron transport and oxidative phosphorylation is 2.5 ATP per NADH and 1.5 ATP per FADH 2 . As a result 9 ATP are generated by electron transport-oxidative phosphorylation per turn of the cycle. Molecular oxygen does not participate in the citric acid cycle. However, the cycle operates only under aerobic conditions because NAD + and FAD cannot be regenerated in the absence of oxygen. Glycolysis has an aerobic and anaerobic mode, but the citric acid cycle only operates under aerobic conditions. I. Regulation of the Citric Acid Cycle TCA Free Energy Changes -140 -120 -100 -80 -60 -40 -20 0 20 40 123456789 Reaction # kJ/mol Reaction DGo' DG
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The citric acid cycle must be carefully regulated by the cell. If the citric acid cycle were permitted to run unchecked, large amounts of metabolic energy would be wasted in the over production of reduced coenzymes and ATP. Conversely if the citric acid cycle ran too slowly, ATP would not be generated fast enough to sustain the cell. By looking at the changes in free energy of the reactions of the citric acid cycle, it is clear that there are three irreversible steps. These three reactions of the cycle, citrate synthase, isocitrate dehydrogenase and α -ketoglutarate dehydrogenase operate with large negative free energy changes under the concentrations of products and reactants in the matrix of the mitochondria. Because the citric acid cycle is linked to oxygen consumption to regenerate NAD + , the citric acid cycle is regulated primarily by product feedback inhibition. Glycolysis and glycogen metabolism are under complex systems of allosteric and hormonal control.
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This note was uploaded on 04/11/2010 for the course BICH bich 411 taught by Professor Bryantmiles during the Spring '10 term at Texas A&M.

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regulationtca - Regulation of the Citric Acid Cycle Bryant...

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