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Updated: Aug 23 2017

Pyruvate Dehydrogenase Complex

  • Introduction
    • Function
      • catalyze conversion of pyruvate to acetyl-CoA
      • net reaction
        • pyruvate + NAD+ + CoA → acetyl-CoA + CO2 + NADH
      • irreversible
    • Structure
      • 3 enzymes that require 5 cofactors
        • thiamine pyrophosphate (B1)
        • FAD (B2)
        • NAD (B3)
        • CoA (B5)
        • lipoic acid
      • similar to α-ketoglutarate dehydrogenase complex
    • Regulation
      • activators of pyruvate dehydrogenase
        • ↓ in energy status of the cell
          • ↑ NAD+/NADH ratio
          • ↑ ADP
        • ↑ exercise
        • ↑ Ca2+
        • ↑ insulin
      • inhibited by acetyl-CoA
    • Clinical relevance
      • pyruvate dehydrogenase deficiency
        • pathophysiology
          • X-linked (variable penetrance in females)
          • accumulation of
            • pyruvate
            • alanine
          • lactic acidosis
            • pyruvate shunted to lactate to regenerate NAD+
        • presentation
          • neurological defects
        • treatment
          • ↑ ketogenic nutrients
            • lysine and leucine
      • arsenic poisoning
        • inhibits pyruvate dehydrogenase
          • via inhibition of lipoic acid
        • presentation
          • vomiting
          • rice water stools
          • garlic breath
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