lipoate

Lipoate, also known as alpha-lipoic acid (ALA), is a sulfur-containing cofactor that supports energy metabolism in mitochondria. It exists in an oxidized form and a reduced form called dihydrolipoic acid, which can be regenerated in cells. In many organisms, the lipoate cofactor is covalently attached as a lipoyl moiety to specific lysine residues on the E2 subunits of several dehydrogenase complexes, including pyruvate dehydrogenase, α-ketoglutarate dehydrogenase, and branched-chain α-keto acid dehydrogenase. The lipoyl group acts as a swinging arm, transferring reaction intermediates between catalytic sites to enable sequential decarboxylation and acyl transfer steps within these multi-enzyme complexes.

Biosynthesis and attachment of the lipoyl cofactor occur in mitochondria and, in bacteria, via lipoyl transferases. The lipoyl group is formed from octanoic acid, with sulfur atoms incorporated by specific enzymes, a process that links lipoate synthesis to cellular energy needs.

Lipoic acid also serves as an antioxidant. The reduced form, dihydrolipoic acid, can scavenge reactive oxygen species and regenerate other antioxidants such as vitamin C, vitamin E, and glutathione. Due to its amphipathic nature, lipoic acid is often described as both water- and fat-soluble, contributing to broad tissue distribution.

Nutritionally, humans can synthesize lipoic acid, and it is not classified as a vitamin. Dietary sources include organ meats, spinach, and other vegetables. Supplements are widely available and have been explored for conditions such as diabetic neuropathy and liver disorders, though clinical evidence for efficacy is variable. Side effects are generally mild, but high doses can cause gastrointestinal upset or interactions with glucose metabolism. Overall, lipoate is a fundamental cofactor in energy production with notable antioxidant properties, and its therapeutic potential continues to be investigated.