Acetyl-coenzyme A carboxylase 1 (ACC1)

Acetyl-coenzyme A carboxylase 1 (ACC1) is a large, multi-domain, biotin-dependent enzyme that catalyzes the ATP-dependent carboxylation of acetyl-CoA to malonyl-CoA, serving as the rate-limiting step in fatty acid synthesis[1][3]. ACC1 is primarily expressed in the cytosol of lipogenic tissues such as liver, adipose tissue, and lactating mammary gland[1]. Through the generation of malonyl-CoA, ACC1 regulates both the biosynthesis of fatty acids and the inhibition of their mitochondrial β-oxidation. The enzyme is tightly controlled at multiple levels—including phosphorylation (by AMP-activated protein kinase and others), allosteric regulation (by citrate), and interaction with protein regulators—making it a focal point for metabolic regulation and pharmaceutical intervention[1][2][4]. ACC1 is encoded by the ACACA gene in humans, while ACC2 is encoded by ACACB and primarily regulates fatty acid oxidation. Dysregulation or overexpression of ACC1 is implicated in a range of metabolic diseases and is an attractive drug target in cancer and metabolic syndrome[4].

Other names

Acetyl-CoA carboxylase 1ACC1ACC alpha (sometimes distinguished from ACC2, but "Acetyl-coenzyme A carboxylase 1" is canonical for ACC1)ACACA (gene symbol)Cytosolic acetyl-CoA carboxylase (distinguishing it from the mitochondrial isoform ACC2)

Inhibition of ACC1 activity prevents malonyl-CoA production, thereby suppressing fatty acid synthesis and potentially promoting fatty acid oxidation\nSmall molecules and natural products (e.g., soraphen A) bind allosteric or catalytic sites to reduce enzyme activity via conformational changes, such as preventing dimerization or domain interactions