Lipoic acid

Lipoic acid (LA), also known as α-lipoic acid, alpha-lipoic acid (ALA) and thioctic acid, is an organosulfur compound derived from caprylic acid (octanoic acid). ALA is made in animals normally, and is essential for aerobic metabolism. It is also manufactured and is available as a dietary supplement in some countries where it is marketed as an antioxidant, and is available as a pharmaceutical drug in other countries. Lipoate is the conjugate base of lipoic acid, and the most prevalent form of LA under physiological conditions. Only the (R)-(+)-enantiomer (RLA) exists in nature and is essential for aerobic metabolism because RLA is an essential cofactor of many enzyme complexes. Lipoic acid (LA), also known as α-lipoic acid, alpha-lipoic acid (ALA), and thioctic acid is an organosulfur compound derived from octanoic acid. LA contains two sulfur atoms (at C6 and C8) connected by a disulfide bond and is thus considered to be oxidized although either sulfur atom can exist in higher oxidation states. 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). LA appears physically as a yellow solid and structurally contains a terminal carboxylic acid and a terminal dithiolane ring. For use in dietary supplement materials and compounding pharmacies, the USP established an official monograph for R/S-LA. Lipoic acid is a cofactor for five enzymes or classes of enzymes: pyruvate dehydrogenase, a-ketoglutarate dehydrogenase, the glycine cleavage system, branched chain keto acid dehydrogenase, and the alpha-oxo(keto)adipate dehydrogenase. The first two are critical to the citric acid cycle. The GCS regulates glycine concentrations. Most endogenously produced RLA are not "free" because octanoic acid, the precursor to RLA, is bound to the enzyme complexes prior to enzymatic insertion of the sulfur atoms. As a cofactor, RLA is covalently attached by an amide bond to a terminal lysine residue of the enzyme's lipoyl domains.