Transcript 5-PDH-and-TCA-cycle - WatCut

Pyruvate degradation occurs in the mitochondria
© Michael Palmer 2014
The PDH reaction occurs in three successive steps
that are catalyzed by three different subunits
© Michael Palmer 2014
The structural organization of the PDH complex
© Michael Palmer 2014
A lipoamide tether guides the substrate from one
active site to the next
© Michael Palmer 2014
The pyruvate dehydrogenase reaction involves
multiple coenzymes
© Michael Palmer 2014
Thiamine pyrophosphate forms a carbanion
© Michael Palmer 2014
Decarboxylation of pyruvate by E1
© Michael Palmer 2014
Release of acetyl-CoA and disposal of hydrogen
© Michael Palmer 2014
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
© Michael Palmer 2014
The overall reaction of the TCA cycle: does it add
up?
© Michael Palmer 2014
The citrate synthase reaction
© Michael Palmer 2014
Reactions in the TCA cycle: from citrate to
succinyl-CoA
© Michael Palmer 2014
Reactions in the TCA: from succinyl-CoA to
oxaloacetate
© Michael Palmer 2014
α-Ketoglutarate dehydrogenase resembles PDH
© Michael Palmer 2014
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