Lipoic acid (LA), also known as alpha-lipoic acid (ALA) is an organosulfur compound derived from octanoic acid. The carbon atom at C6 is chiral and the molecule exists as two enantiomers (R)-(+)-lipoic acid (RLA) and (S)-(-)-lipoic acid (SLA) and as a racemic mixture (R/S)-lipoic acid (R/S-LA). Only the (R)-(+)-enantiomer exists in nature and is an essential cofactor of four mitochondrial enzyme complexes. Endogenously synthesized RLA is essential for life and aerobic metabolism. The precursor to lipoic acid, octanoic acid, is made via fatty acid biosynthesis in the form of octanoyl-acyl carrier protein. In eukaryotes, a second fatty acid biosynthetic pathway in mitochondria is used for this purpose. The octanoate is transferred from a thioester of acyl carrier protein to an amide of the lipoyl domain by an octanoyltransferase. The sulfur centers are inserted into the 6th and 8th carbons of octanoate via a radical SAM mechanism, by lipoyl synthase. Lipoic acid can be removed whenever proteins are degraded and by the action of the enzyme lipoamidase. Free lipoate can be attached to the lipoyl domain by the enzyme lipoate protein ligase. The ligase activity of this enzyme requires ATP. Lipoate protein ligases proceed via an enzyme-bound lipoyl adenylate intermediate. Both RLA and R/S-LA are available as over-the-counter nutritional supplements and have been used nutritionally and clinically since the 1950s for various diseases and conditions. It is often regarded as a vitamin-like antioxidant. Lipoic acid is generally involved in oxidative decarboxylations of keto acids and is presented as a growth factor for some organisms. Some studies have suggested that the S-enantiomer has an inhibiting effect on the R-enantiomer, reducing its biological activity substantially and adding to oxidative stress rather than reducing it (PMID: 8573188, 7669066). Furthermore, the S-enantiomer has been found to reduce the expression of GLUT-4s in cells, responsible for glucose uptake, and hence reduce insulin sensitivity (PMID: 9252495).