Figure 2.

Lipoic acid is a cofactor of mitochondrial 2-ketoacid dehydrogenase complex, including pyruvate dehydrogenase complex, α-ketoglutarate dehydrogenase complex, and branched-chain amino acid dehydrogenase complex. The E1 subunit is 2-ketoacid decarboxylase using TPP as a cofactor; the E2 subunit is a dihydrolipoamide acyltransferase using lipoic acid as a cofactor; the E3 subunit is a dihydrolipoamide dehydrogenase, which uses NAD⁺ as an electron acceptor for the oxidation of the lipoyl group linked to the E2 subunit. E3 catalyzes the formation of the oxidized form of lipoic acid and generates NADH in the meantime [32,33,34].