Acetyl-CoA carboxylase complex (ACC)

**Acetyl-CoA carboxylase complex** is a biotin-dependent enzyme that catalyzes the ATP-dependent carboxylation of acetyl-CoA to malonyl-CoA, the first and rate-limiting step in the synthesis of fatty acids[1][2][3]. ACC exists as a complex of subunits in prokaryotes and as large multi-domain single-chain enzymes in eukaryotes, with two main isoforms in mammals: ACC1 (cytosolic, for fatty acid synthesis) and ACC2 (mitochondrial, involved in regulating fatty acid oxidation)[1][2][4][7]. ACC activity is highly regulated at the transcriptional, post-translational, and allosteric levels, serving as a pivotal metabolic control point integrating hormonal and nutritional signals[1][6]. The enzyme is a validated therapeutic target in metabolic diseases (like obesity and diabetes), as well as in cancer, due to its central role in lipid metabolism and cell proliferation[2][4][7]. Several synthetic inhibitors (including CP-640186 and Soraphen A) and herbicides (targeting plant ACC) demonstrate the broad relevance of ACC inhibition in both medicine and agriculture[4].

Other names

Acetyl-CoA carboxylaseACC complexAcetyl-coenzyme A carboxylaseFatty acid synthase (historically, but not specifically)Acetyl-CoA carboxylase 1 (ACC1)Acetyl-CoA carboxylase 2 (ACC2)

Inhibition of fatty acid synthesis (inhibitors block carboxylation of acetyl-CoA, reducing malonyl-CoA formation and thus new fatty acid synthesis)[4][7] Inhibition of regulation of fatty acid oxidation (inhibitors affecting ACC2 reduce malonyl-CoA in mitochondria, disinhibiting carnitine palmitoyltransferase I and increasing fatty acid β-oxidation)[4]