Acetyl-CoA carboxylase 2

Definition:

Mitochondrial enzyme that catalyzes the carboxylation of acetyl-CoA to malonyl-CoA and plays a central role in fatty acid metabolism. Catalyzes a 2 steps reaction starting with the ATP-dependent carboxylation of the biotin carried by the biotin carboxyl carrier (BCC) domain followed by the transfer of the carboxyl group from carboxylated biotin to acetyl-CoA. Through the production of malonyl-CoA that allosterically inhibits carnitine palmitoyltransferase 1 at the mitochondria, negatively regulates fatty acid oxidation (By similarity). Together with its cytosolic isozyme ACACA, which is involved in de novo fatty acid biosynthesis, promotes lipid storage (By similarity).

References:

[1]. Christopher L Colbert, et al. Crystal structure of Spot 14, a modulator of fatty acid synthesis. Proc Natl Acad Sci U S A. 2010 Nov 2;107(44):18820-5. [Content Brief]

[2]. Virendar K Kaushik, et al. Characterization of recombinant human acetyl-CoA carboxylase-2 steady-state kinetics. Biochim Biophys Acta. 2009 Jun;1794(6):961-7. [Content Brief]

[3]. Yong Soon Cho, et al. Molecular mechanism for the regulation of human ACC2 through phosphorylation by AMPK. Biochem Biophys Res Commun. 2010 Jan 1;391(1):187-92. [Content Brief]

[4]. Dong Cheng, et al. Expression, purification, and characterization of human and rat acetyl coenzyme A carboxylase (ACC) isozymes. Protein Expr Purif. 2007 Jan;51(1):11-21. [Content Brief]

[5]. Chai-Wan Kim, et al. Induced polymerization of mammalian acetyl-CoA carboxylase by MIG12 provides a tertiary level of regulation of fatty acid synthesis. Proc Natl Acad Sci U S A. 2010 May 25;107(21):9626-31. [Content Brief]

[6]. Geraldine Harriman, et al. Acetyl-CoA carboxylase inhibition by ND-630 reduces hepatic steatosis, improves insulin sensitivity, and modulates dyslipidemia in rats. Proc Natl Acad Sci U S A. 2016 Mar 29;113(13):E1796-805. [Content Brief]

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