dihydrolipoamide

Dihydrolipoamide is the reduced form of lipoamide, the amide of lipoic acid with a lysine residue on the E2 subunit of mitochondrial dehydrogenase complexes. It is an intermediate carrier within the catalytic cycles of several enzyme complexes, including the pyruvate dehydrogenase complex (PDH), alpha-ketoglutarate dehydrogenase complex (KGDH), and branched-chain ketoacid dehydrogenase (BCKDH).

In the PDH cycle, after decarboxylation of pyruvate by E1, the acetyl group is transferred to the lipoamide arm to form acetyl-dihydrolipoamide. The acetyl group is then transferred to CoA to produce acetyl-CoA, leaving the lipoamide in a reduced state with two free thiol groups. Dihydrolipoamide dehydrogenase (E3) reoxidizes dihydrolipoamide back to lipoamide by transferring electrons to FAD and then to NAD+, generating NADH in the process. This regeneration restores the lipoamide arm for subsequent catalytic turns.

In its oxidized form, lipoamide contains a disulfide bond; in dihydrolipoamide, this bond is reduced to two thiol groups. The term refers specifically to the reduced, E2-bound form rather than the free lipoic acid. Dihydrolipoamide therefore serves as a temporary carrier of acetyl and other acyl groups during oxidative decarboxylation reactions in mitochondrial metabolism.