lipoyldithiol

Lipoyldithiol refers to the reduced form of the lipoyl moiety, a component of the lipoic acid–dependent enzyme system. In this state, the 1,2-dithiolane ring of lipoic acid bears two free thiol groups (-SH), giving dihydrolipoamide as the functional form. The lipoyl group is covalently attached to a lysine residue on the E2 subunit of several dehydrogenase complexes, most notably the pyruvate dehydrogenase complex, but also branched-chain α-ketoacid dehydrogenase and α-ketoglutarate dehydrogenase.

Structure and redox cycling

Lipoyldithiol features two thiol groups on adjacent sulfur atoms in the reduced lipoic acid ring. During catalytic turnover, the lipoyl arm serves as a swinging tether that transfers intermediates between active sites. In the catalytic cycle, the lipoyl group is briefly reduced to lipoyldithiol while accepting acyl or acetyl groups, and is then reoxidized back to the disulfide form by the FAD-dependent enzyme dihydrolipoamide dehydrogenase (E3), with NAD+ as the ultimate electron acceptor. This redox cycling enables efficient substrate channeling within multi-enzyme complexes.

Biological relevance

Lipoyldithiol is essential for aerobic metabolism in mitochondria and bacteria, enabling the oxidative decarboxylation of pyruvate and α-ketoacids and the generation of acetyl-CoA and NADH. Disruption of lipoyl-bearing enzymes or their redox partner can impair energy production and lead to metabolic dysfunction. Lipoyl modification is also a focal point in studies of lipoic acid biosynthesis, protein lipoylation, and related regulatory mechanisms.

See also

Lipoyllysine, lipoic acid, dihydrolipoamide dehydrogenase.