PYRUVATE DEHYDROGENASE COMPLEX (PDC)

• Pyruvate + CoA + NAD+ –> Acetyl CoA + CO2 + NADH
• Located in mitochondrial matrix
• Irreversible reaction

PDC ENZYMES

E1, pyruvate dehydrogenase/pyruvate decarboxylase

• Catalyzes pyruvate to acetyl (releases CO2)
• Cofactor: thiamine pyrophosphate (Vitamin B1)

E2, dihydrolipoyl transacetylase

• Attaches CoA to acetyl
• Cofactor: lipoic acid (not vitamin-derived) & coenzyme A (pantothenic acid/vitamin B5)

E3, dihydrolipoyl dehydrogenase

• Reduces NAD+ to NADH
• Cofactor: NAD+ (niacin/vitamin B3) & FAD (riboflavin/vitamin B2)

Lipoic acid is only cofactor for PDC that is not vitamin-derived

CLINICAL CORRELATION

PDC-based pathology

• Deficiencies in vitamins or PDC cofactors produce initial neurological/muscular symptoms