The carboxylases allow the production of new carbon-carbon bonds by introducing HCO₃^- or CO₂ into target molecules. Two groups of carboxylase activities, some of which are bidirectional, can be defined on the basis of the cofactor requirement, making use of biotin (EC 6.4.1.-) or vitamin K hydroquinone (EC 4.1.1.-).

Dicarboxylic acids including citric acid are able to activate ACC1/ACC2 activity allosterically. PCC is able to function in forward and reverse modes as a ligase (carboxylase) or lyase (decarboxylase) activity, respectively. Loss-of-function mutations in GGCX are associated with clotting disorders.

* Key recommended reading is highlighted with an asterisk

* Tong L. (2005) Acetyl-coenzyme A carboxylase: crucial metabolic enzyme and attractive target for drug discovery. Cell Mol Life Sci, 62 (16): 1784-803. [PMID:15968460]

* Wang Y, Yu W, Li S, Guo D, He J, Wang Y. (2022) Acetyl-CoA Carboxylases and Diseases. Front Oncol, 12: 836058. [PMID:35359351]

1. Griffith DA, Dow RL, Huard K, Edmonds DJ, Bagley SW, Polivkova J, Zeng D, Garcia-Irizarry CN, Southers JA, Esler W et al.. (2013) Spirolactam-based acetyl-CoA carboxylase inhibitors: toward improved metabolic stability of a chromanone lead structure. J Med Chem, 56 (17): 7110-9. [PMID:23981033]

2. Harriman G, Greenwood J, Bhat S, Huang X, Wang R, Paul D, Tong L, Saha AK, Westlin WF, Kapeller R et al.. (2016) Acetyl-CoA carboxylase inhibition by ND-630 reduces hepatic steatosis, improves insulin sensitivity, and modulates dyslipidemia in rats. Proc Natl Acad Sci USA, 113 (13): E1796-805. [PMID:26976583]

3. Takagi H, Tanimoto K, Shimazaki A, Tonomura Y, Momosaki S, Sakamoto S, Abe K, Notoya M, Yukioka H. (2020) A Novel Acetyl-CoA Carboxylase 2 Selective Inhibitor Improves Whole-Body Insulin Resistance and Hyperglycemia in Diabetic Mice through Target-Dependent Pathways. J Pharmacol Exp Ther, 372 (3): 256-263. [PMID:31900320]

4. Waring JF, Yang Y, Healan-Greenberg CH, Adler AL, Dickinson R, McNally T, Wang X, Weitzberg M, Xu X, Lisowski A et al.. (2008) Gene expression analysis in rats treated with experimental acetyl-coenzyme A carboxylase inhibitors suggests interactions with the peroxisome proliferator-activated receptor alpha pathway. J Pharmacol Exp Ther, 324 (2): 507-16. [PMID:18025247]

5. Zhou W, Simpson PJ, McFadden JM, Townsend CA, Medghalchi SM, Vadlamudi A, Pinn ML, Ronnett GV, Kuhajda FP. (2003) Fatty acid synthase inhibition triggers apoptosis during S phase in human cancer cells. Cancer Res, 63 (21): 7330-7. [PMID:14612531]