Citric Acid Cycle: A Two Stage Process

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Presentation transcript:

Citric Acid Cycle Generates Reductive Equivalents Utilized in Respiration

Citric Acid Cycle: A Two Stage Process Stage One: C4 + C2 condensation C6 tricarboxylic acid Oxidative decarboxylation 2 CO2 Succinyl CoA Net Result: 2NADH + 2CO2 + Succinyl CoA

C4 + C2 Condensation Reaction Condensation catalyzed by enzyme dimer Citrate Synthase RxN Driver

Citrate Synthase Reaction

Citrate Synthase Reaction

Citrate Synthase Reaction

Citrate Synthase Reaction

Citrate to Isocitrate Conversion via Aconitase Hydroxyl shift for subsequent oxidative decarboxylation

Isocitrate Dehydrogenase: Oxidation and Decarboxylation Oxalosuccinate not released from the enzyme

α-Ketoglutarate Dehydrogenase: Oxidation and Decarboxylation How similar is α-ketoglutarate dehydrogenase with pyruvate dehydrogenase in terms of substrate components? Reaction mechanism?

Citric Acid Cycle Part Two: Oxaloacetate Regeneration Succinyl Coenzyme A Synthetase couples hydrolysis of Coenzyme A (-33 kJ/mol) with GTP formation (-30 kJ/mol) The energetics works but what about the reaction mechanism?

Succinyl CoA-Sythetase Generates GTP What is the Nu:-, E, and leaving group with GTP generation?

Oxaloacetate Enzyme Regeneration from Succinate Succinate Dehydrogenase Fumerase Malate Dehydrogenase

A Color-Coded Citric Acid Cycle Isocitrate is prochiral Succinate is a symmetric molecule Generated products include: 2CO2 + 3NADH + 1FADH2 + GTP + CoA

Citric Acid Energetics

Citric Acid Cycle Regulation Points ATP and NADH are indicators of a high energy state ADP an indicator of a low energy state Regulatory sites include: Isocitrate dehydrogenase α-Ketoglutarate dehydrogenase Pyruvate dehydrogenase

Citric Acid Cycle is a Source for Biosynthetic Precursors

Transamination Reaction

Citric Acid Cycle Intermediates: Replenished as Metabolites are Drawn Off for Biosynthesis Anapleurotic reactions lead to a replenishment of pathway components (e.g. pyruvate carboxylase).

Problems: 1, 3, 5, 7 and 9