Acyl-CoA thioesterase (ACOT)

Acyl-CoA thioesterases (abbreviated ACOT; also commonly referred to as thioesterases) are enzymes belonging to the hydrolase class (specifically EC 3.1.2) that catalyze the hydrolysis of thioester bonds in acyl-CoA molecules, releasing free fatty acids and coenzyme A. They play essential roles in regulating fatty acid metabolism, lipid biosynthesis, mitochondrial and peroxisomal β-oxidation, signaling molecule production, and cellular energy homeostasis. Multiple ACOT family members exist in humans, each with unique tissue distribution, substrate specificity, and regulatory domains. Thioesterases have implications in diverse physiological and disease states, including metabolic disorders, neurodegeneration, cancer, and infection, making them a potential, yet complex, drug target.

Other names

ThioesteraseThioester hydrolaseAcyl-CoA hydrolaseACOTTE (less specific, sometimes used in the literature)ARTISt (rare/less common abbreviation)

Inhibition or modulation of thioesterase activity leads to altered fatty acid and lipid metabolic flux, which can modulate energy production, lipogenesis, and cell signaling pathways. Potential action includes accumulation or depletion of acyl-CoA or free fatty acids, rerouting metabolic pathways, or preventing/inducing cell proliferation and apoptosis in disease contexts.