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Regulation (pyruvate dehydrogenase)

Last reviewed dd mmm yyyy. Last edited dd mmm yyyy

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Pyruvate dehydrogenase exists in 2 forms. The a form (PDa) is active and dephosphorylated. It is phosphorylated to the inactive b form (PDb) by the enzyme pyruvate dehydrogenase kinase. PDb is dephosphorylated back to PDa by the enzyme pyruvate dehydrogenase phosphatase.

Pyruvate dehydrogenase kinase is activated by:

  • increasing acetyl CoA relative to coenzyme A
  • increasing NADH relative to NAD
  • increasing ATP relative to ADP

Pyruvate dehydrogenase kinase is inhibited by an increasing concentration of pyruvate.

Pyruvate dehydrogenase phosphatase is stimulated by increasing calcium concentration.

Hence, any index of a low energy status within the cell e.g. low ATP, or activation of muscular contraction by increase in calcium concentration, stimulates increased production of acetyl CoA.

One corollary of increased concentrations of acetyl CoA inhibiting pyruvate dehydrogenase is that lipolysis, with the production of acetyl CoA, inhibits the entry of glycolytic pyruvate into the TCA cycle. This is a means of conserving glucose during times of stress.


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