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Unformatted text preview: Chapter 16The Citric Acid Cycle Overview Part 1 Pyruvate-the product of glycolysis is converted to acetyle-CoA, the starting material for the citric acid cycle by the PDH Complex . The PDH complex is composed of 3 enzymes, pyruavte dehydrogenase---cofactor=TPP, dihydrolipoyl transacetylasecofactor=lipoamide arm, and dihydrolipoyl dehydrogenase---cofactor=FAD and NAD Reactions of Citric Acid Cycle Overview Catabolic pathway where compounds are derived from the break down of carbs, fats, and proteins--- they are oxidized to CO2 Most of the energy for oxidation is held in FADH2 and NADH----these electrons are transferred to O2 and the energy of electron flow is trapped as ATP Acetyl-CoA enter cycle as citrate synthase catalyzes its condensation with oxaloacetate to form citrate 7 RXS 2 carboxylations---cycles converts citrate to oxaloacetate and releases 2 CO2---cyclic in that the intermediates of the cycle are not used up For each acetyl-CoA oxidized in the cycle, the energy gain consists of 3 molecules of NADH, one FADH2 and on TP (either ATP or GTP) It is amphibolic- serving as both anabolism and catabolism When intermediates are shunted from the cycle to other pathways they are replenished by several anaplerotic reactions, which produce 4-C intermediates by the carboxylation of 3-C compounds----these are catalyzed by pyruavte carboxylase , PEP carboxykinase, PEP carboxylase and malice enzyme ---often employ biotin to activate CO2 and carry it to acceptors such as pyruavte Step by Step 1. Formation of Citrate Condensation of acetyl-CoA with oxaloacetate to form citrate, catalyzed by citrate synthase 2. Formation of Isocitrate via cis-Aconitate Enzyme aconitate catalyzes reversible rxn of citrate to Isocitrate through the intermediary formation of the tricarboxylic acid cis-aconitate 3. Oxidation of Isocitrate to a-Ketoglutarate and CO2 Isocitrate dehydrogenase catalyzes oxidative carboxylation to form a-ketoglutarate Mn2+ in active site interacts with carbonyl group NAD+ is reduced to NADH 4. Oxidation of a-ketoglutarate to Succinyl-CoA and CO2 NAD+ serves as electron acceptor and CoA as the carrier of the succinyl group Co-ASH comes in to make succinyl CoA thioester. 5. Conversion of Succinyl-CoA to Succinate Succinyl-CoA has a thioester bond with very high negative energy of hydrolysis Molecule becomes phosphorylated at a His residue in the active site This phosphoryl group is transferred to ADP to form ATP Succinyl-CoA + GDP --------Succinate + GTP 6. Oxidation of Succinate to Fumerate Done by flavoprotein Succinate dehydrogenasewhich is tightly bound to inner mitochondrial membrane---it contains 3 Fe-S clusters and one covalently linked FAD Electrons pass from Succinate to FAD and Fe-S centers before entering the chain of electron carriers Succinate + FAD-----------Fumerate + FADH2 7. Hydration of Fumerate to Malate Reversible hydration of Fumerate to L-Malate is catalyzed by fumerase...
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This note was uploaded on 03/26/2008 for the course BIOBM 3300 taught by Professor Blankenshi during the Spring '08 term at Cornell University (Engineering School).
- Spring '08