Coenzyme A-dependent enzyme (CoA-dependent enzyme)

Coenzyme A (CoA)-dependent enzymes constitute a vast and essential functional class of proteins, representing approximately 4% of all cellular enzymes, that utilize CoA or its thioester derivatives as substrates, products, or cofactors [1.2.1, 1.3.1]. These enzymes are central to primary metabolism, facilitating critical pathways such as the tricarboxylic acid (TCA) cycle, fatty acid biosynthesis and beta-oxidation, and the synthesis of cholesterol, ketone bodies, and heme [1.1.2, 1.3.1]. Beyond energy production, they play vital roles in signal transduction and gene expression through the post-translational modification of proteins via acetylation and the synthesis of neurotransmitters like acetylcholine [1.1.1, 1.3.2]. Due to their fundamental roles in metabolic homeostasis, many CoA-dependent enzymes are major therapeutic targets; for instance, HMG-CoA reductase is the target of statins for treating hypercholesterolemia, while others like acetyl-CoA carboxylase and ATP-citrate lyase are targeted for metabolic diseases and cancer [1.4.2, 1.4.3]. Dysregulation or genetic mutations in these enzymes are linked to a wide range of pathologies, including cardiovascular disease, diabetes, oncology, and rare neurodegenerative disorders such as pantothenate kinase-associated neurodegeneration (PKAN) [1.1.3, 1.1.4]. Pharmacological intervention typically involves small-molecule inhibitors that compete with CoA or its acyl-thioesters for binding sites, thereby modulating lipid profiles or cellular energy balance [1.2.1, 1.4.3]. In addition to human health, these enzymes are explored as targets for novel antimicrobials, as bacterial fatty acid synthesis and CoA biosynthesis pathways often differ significantly from their human counterparts [1.2.2, 1.2.5].

Other names

CoA-utilizing enzymeCoenzyme A-linked enzymeAcyl-CoA dependent enzyme

Inhibition of specific enzymes within the class, such as HMG-CoA reductase, ATP-citrate lyase, or acetyl-CoA carboxylase, to modulate lipid metabolism and cellular energy levels [1.4.2, 1.4.3].