Pyruvate degradation occurs in the mitochondria Michael Palmer 2014.

Pyruvate degradation occurs in the mitochondria

© Michael Palmer 2014

The PDH reaction occurs in three successive steps that are catalyzed by three different subunits


The structural organization of the PDH complex


A lipoamide tether guides the substrate from one active site to the next


The pyruvate dehydrogenase reaction involves multiple coenzymes


Thiamine pyrophosphate forms a carbanion


Decarboxylation of pyruvate by E1


Release of acetyl-CoA and disposal of hydrogen


Alternate metabolic destinations of pyruvate

1. conversion to acetyl-CoA by PDH for complete degradation or for synthesis of fatty acids and cholesterol

2. carboxylation to oxaloacetate, for use in gluconeogenesis or in the citric acid cycle

3. synthesis of amino acids, e.g., transamination to alanine

4. reduction to lactate

Regulation of PDH by allosteric effectors and by phosphorylation


The overall reaction of the TCA cycle: does it add up?


The citrate synthase reaction


Reactions in the TCA cycle: from citrate to succinyl-CoA


Reactions in the TCA: from succinyl-CoA to oxaloacetate


α-Ketoglutarate dehydrogenase resembles PDH


Regulation of the citric acid cycle

● ATP and NADH inhibit isocitrate dehydrogenase ● NADH inhibits α-ketoglutarate dehydrogenase ● High levels of NADH will lower the oxaloacetate

concentration, which limits citrate synthase activity

Pyruvate degradation occurs in the mitochondria Michael Palmer 2014.

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