PDH is a multi-enzyme complex composed of three main components: E1 (pyruvate dehydrogenase), E2 (dihydrolipoamide transacetylase), and E3 (dihydrolipoamide dehydrogenase). The catalytic mechanism involves multiple steps:
E1 catalyzes the decarboxylation of pyruvate, yielding a hydroxyethyl-TPP intermediate. In E2, the hydroxyethyl group is transferred to lipoamide, forming acetyl-lipoamide. Finally, E3 regenerates the oxidized form of lipoamide and produces NADH from NAD+.