Biochemistry

The metabolic functions of pantothenic acid in human biochemistry are mediated through the synthesis of CoA (Fig. 28.33). 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 acyl-CoA derivatives. Pantothenic acid also 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 diphosphate and lipoic acid, two other important coenzymes. Thiamine diphosphate is the actual decarboxylating coenzyme that functions with lipoic acid to form acetyldihydrolipoic acid from pyruvate decar-boxylation. CoA then accepts the acetyl group from acetyldihydrolipoic 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, acyl proteins, porphyrins, and acetylcholine). CoA is also intimately involved in the growth of microorganisms, including those pathogenic to humans. This has led to the novel strategy of developing pantothenic acid analogs that selectively inhibit pantothenic acid utilization and/or

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