Deficiency of the pyruvate dehydrogenase complex (PDHC)

PDHC is a mitochondrial multienzyme system that catalyzes the oxidation of pyruvate to CO2 and acetyl CoA and concomitantly generates reduced nicotinamide adenine dinucleotide (NADH) (Figure 50.1) [1]. Cofactors include thiaminepyrophosphate (TPP), lipoic acid, coenzyme A (CoA), flavine adenine dinucleotide (FAD) and nicotinamide adenine dinucleotide (NAD); Mg2 is required. There are six different protein components, in five of which human deficiency disease has been documented. The three basic components (E1, E2 and E3) are functional catalytic proteins, of types that are shared by all oxoacid dehydrogenases.