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