Fig. 1

Regulation mechanisms of α-KGDC. α-KGDC is a complex consisting of multiple copies of three enzymes: α-ketoglutarate dehydrogenase (E1), dihydrolipoamide succinyltransferase (E2), and dihydrolipoamide dehydrogenase (E3). α-KG reacts with the TPP that binds E1, and is thereby a decarboxylated-generating hydroxyethyl compound. E1 also catalyzes the transfer of two electrons and the acetyl group of the TPP on lipoic acid (LA), which is bound to the E2 subunit. The reaction performed by E2 is a transesterification in which the thiol group of the Coenzyme A (CoA) replaces the thiol group of E2, producing Succ-CoA and the reduced form of the lipoic group, the dihydrolipoic acid (DHLA). The subunit E3 catalyzes the transfer of two atoms of hydrogens from DHLA to its prosthetic group FAD, restoring oxidized LA. The reduced FADH₂ of the E3 enzyme transfer H⁺ to NAD⁺ to form NADH.