Acetyl-coenzyme A thioesterase (ACOT12)

Acetyl-coenzyme A thioesterase (ACOT12) is an enzyme that catalyzes the hydrolysis of acetyl-CoA and related thioesters to free CoA and the corresponding acid, playing an essential role in regulating intracellular acetyl-CoA levels and lipid metabolism. It is a member of the acyl-CoA thioesterase enzyme family and is responsible for maintaining the cytosolic pool of acetyl-CoA in the liver and possibly other tissues. ACOT12 is structurally characterized by two thioesterase domains, with binding site selectivity for short-chain acyl-CoAs, especially acetyl-CoA, and its activity is allosterically modulated by intracellular lipid metabolites and energy charge (ATP/ADP). Biological consequences of altered ACOT12 activity extend to fatty acid synthesis, gluconeogenesis, ketone body metabolism, and eicosanoid signaling. Dysregulation is linked to metabolic disease, inflammation, and potentially cancer, making it an emerging though underexplored therapeutic target.

Other names

Acyl-CoA thioesterase 12ACOT12Acetyl-CoA hydrolaseAcetyl-CoA thioester hydrolaseCytosolic acyl-CoA thioesterase

Enzyme inhibition: Blocking ACOT12 prevents hydrolysis of acetyl-CoA, elevating its intracellular concentration; Enzyme activation: Increasing ACOT12 activity lowers cellular acetyl-CoA, affecting downstream lipid metabolic pathways