Coenzyme A (CoA) (CoA)

Coenzyme A (CoA) is a fundamental metabolic cofactor and acyl group carrier essential for all living organisms [1.1.1, 1.3.2]. It plays a central role in the oxidation of pyruvate in the citric acid cycle, the synthesis and oxidation of fatty acids, and the production of cholesterol, ketone bodies, and heme [1.1.2, 1.3.3]. Beyond its classical metabolic roles, CoA is involved in the post-translational modification of proteins through acetylation and the regulation of gene expression via histone modification [1.3.2, 1.4.2]. Dysregulation of CoA metabolism is linked to various pathologies, including neurodegenerative disorders like pantothenate kinase-associated neurodegeneration (PKAN), cancer metabolic reprogramming, and cardiovascular diseases [1.2.4, 1.3.1]. Therapeutic strategies targeting CoA include the development of antimicrobial antimetabolites and small-molecule activators of CoA biosynthesis to restore levels in deficiency states [1.2.1, 1.4.4]. Additionally, CoA serves as a precursor for the 4'-phosphopantetheine prosthetic group in acyl carrier proteins, which are critical for fatty acid and polyketide biosynthesis [1.1.5]. Recent research has also identified protein CoAlation as a redox-regulated post-translational modification where CoA forms disulfide bonds with protein cysteines during oxidative stress [1.3.2, 1.4.4]. This modification can alter the activity and stability of metabolic enzymes, suggesting a broader role for CoA in cellular signaling and stress response [1.3.5, 1.4.4].

Other names

CoA-SHCoASHHS-CoA3'-phosphoadenosine-5'-diphosphopantetheine

Drugs targeting Coenzyme A metabolism typically act as antimetabolites that are converted into inactive CoA analogs (anti-CoAs), or as allosteric activators of biosynthetic enzymes like pantothenate kinase to increase intracellular CoA levels.