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 ReactionCondensation 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 AconitaseHydroxyl 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