Lipoic acid biochemistry

In addition, CS reacts with the disulfhydryl form of lipoic acid, a coenzyme in the pymvate decarboxylase system (Olajos and Salem, 2001). Alteration in dihydro-lipoic acid biochemistry can lead to decreased acetyl CoA levels, resulting in cellular injury. Therefore, tissue injury seems to be related to inactivation of these metabolic enzyme systems. The damage is transient because the enzymes can be rapidly reactivated if exposure is terminated (Beswick, 1983). 

Shepherd, G. B. Hammes, G. G. Fluorescence energy transfer measurements in the pyruvate dehydrogenase multienzyme complex from Escherichia coli with chemically modified lipoic acid. Biochemistry 1977, 16, 5234-5240. 

Lipoic acid (6,8-dithiooctanoic acid) was isolated and characterized in 1951 in studies that showed that it was required for the growth of certain bacteria and protozoa. This accomplishment was one of the most impressive feats of isolation in the early history of biochemistry. Eli Lilly and Co., in cooperation with Lester J. Reed at the University of Texas and I. C. Gunsalus at the... 

The metabolic functions of pantothenic acid in human biochemistry are mediated through the synthesis of CoA. Pantothenic acid is a structural component of CoA. which is necessary for many important metabolic processes. Pantothenic acid is incorporated into CoA by a. series of five enzyme-catalyzed reactions. CoA is involved in the activation of fatty acids before oxidation, which requires ATP to form the respective fatty ocyl-CoA derivatives. Pantothenic acid aI.so participates in fatty acid oxidation in the final step, forming acetyl-CoA. Acetyl-CoA is also formed from pyruvate decarboxylation, in which CoA participates with thiamine pyrophosphate and lipoic acid, two other important coenzymes. Thiamine pyrophosphate is the actual decarboxylating coenzyme that functions with lipoic acid to form acetyidihydrolipoic acid from pyruvate decarboxylation. CoA then accepts the acetyl group from acetyidihydrolipoic acid to form acetyl-CoA. Acetyl-CoA is an acetyl donor in many processes and is the precursor in important biosyntheses (e.g.. those of fatty acids, steroids, porphyrins, and acetylcholine). 

The chemistry of the cofactors has provided a fertile area of overlap between organic chemistry and biochemistry, and the organic chemistry of the cofactors is now a thoroughly studied area. In contrast, the chemistry of cofactor biosynthesis is still relatively underdeveloped. In this review the biosynthesis of nicotinamide adenine dinucleotide, riboflavin, folate, molyb-dopterin, thiamin, biotin, lipoic acid, pantothenic acid, coenzyme A, S-adenosylmethionine, pyridoxal phosphate, ubiquinone and menaquinone in E. coli will be described with a focus on unsolved mechanistic problems. 

The reactions in which pyruvic acid is oxidized to form CO2 and acetic acid are of the greatest significance since they constitute the link between glycolysis and the Krebs cycle. These reactions involve a considerable number of coenzymes thiamine pyrophosphate, lipoic acid, Co A, and NAD. Much of our knowledge of pyruvic acid oxidation depended on the discovery of CoA and lipoic acid, and it might be useful to review the biochemistry of lipoic acid before we enter into more detail. Refer to the chapter on vitamins for a review of the metabolism and catabolism of thiamine, CoA, and NAD. 

Schmidt, U., Altland, K., Goedde, H.W. Biochemistry and chemistry of lipoic acids. Advanc. Enzymol. 32, 423-469 (1969)... 

Zempleni, J., McCormick, D.B., Stratton, S.L., and Mock, D.M., 1996. Lipoic acid (thioctic add) analogs, tryptophan analogs, andurea do not interfere with the assay of biotin and biotin metabolites by high-performance liquid chromatography/avidin-binding assay. The Journal of Nutritional Biochemistry. 1 518 523. 

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