ACACB
Acetyl-CoA carboxylase 2 also known as ACC-beta or ACC2 is an enzyme that in humans is encoded by the ACACB gene.[1][2]
Function
Acetyl-CoA carboxylase (ACC) is a complex multifunctional enzyme system. ACC is a biotin-containing enzyme which catalyzes the carboxylation of acetyl-CoA to malonyl-CoA, the rate-limiting step in fatty acid synthesis. ACC-beta is thought to control fatty acid oxidation by means of the ability of malonyl-CoA to inhibit carnitine palmitoyltransferase I, the rate-limiting step in fatty acid uptake and oxidation by mitochondria. ACC-beta may be involved in the regulation of fatty acid oxidation, rather than fatty acid biosynthesis.[1]
Clinical implications
Human acetyl-CoA carboxylase has recently become a target in the design of new anti-obesity drugs.[3] However when the gene for ACC2 was knocked out in mice, no change in body weight was observed relative to normal mice.[4] This result suggests inhibition of ACC2 by drugs may be an ineffective method of treating obesity.
References
- ^ a b "Entrez Gene: acetyl-Coenzyme A carboxylase beta". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=32.
- ^ Widmer J, Fassihi KS, Schlichter SC, Wheeler KS, Crute BE, King N, Nutile-McMenemy N, Noll WW, Daniel S, Ha J, Kim KH, Witters LA (June 1996). "Identification of a second human acetyl-CoA carboxylase gene". Biochem. J. 316 ( Pt 3): 915–22. PMC 1217437. PMID 8670171. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1217437.
- ^ Corbett JW, Harwood JH (November 2007). "Inhibitors of mammalian acetyl-CoA carboxylase". Recent Patents Cardiovasc Drug Discov 2 (3): 162–80. doi:10.2174/157489007782418928. PMID 18221116.
- ^ Olson DP, Pulinilkunnil T, Cline GW, Shulman GI, Lowell BB (April 2010). "Gene knockout of Acc2 has little effect on body weight, fat mass, or food intake". Proc Natl Acad Sci U S A 107 (16): 7598–7603. doi:10.1073/pnas.0913492107. PMC 2867727. PMID 20368432. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2867727.
Further reading
- Cheng D, Chu CH, Chen L, et al. (2007). "Expression, purification, and characterization of human and rat acetyl coenzyme A carboxylase (ACC) isozymes". Protein Expr. Purif. 51 (1): 11–21. doi:10.1016/j.pep.2006.06.005. PMID 16854592.
- Diaz FJ, Meary A, Arranz MJ, et al. (2009). "Acetyl-coenzyme A carboxylase alpha gene variations may be associated with the direct effects of some antipsychotics on triglyceride levels". Schizophr. Res. 115 (2–3): 136–40. doi:10.1016/j.schres.2009.09.038. PMC 2784140. PMID 19846279. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2784140.
- Madauss KP, Burkhart WA, Consler TG, et al. (2009). "The human ACC2 CT-domain C-terminus is required for full functionality and has a novel twist". Acta Crystallogr. D Biol. Crystallogr. 65 (Pt 5): 449–61. doi:10.1107/S0907444909008014. PMC 2725780. PMID 19390150. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2725780.
- Kahn BB, Alquier T, Carling D, Hardie DG (2005). "AMP-activated protein kinase: ancient energy gauge provides clues to modern understanding of metabolism". Cell Metab. 1 (1): 15–25. doi:10.1016/j.cmet.2004.12.003. PMID 16054041.
- de Leon J, Correa JC, Ruaño G, et al. (2008). "Exploring genetic variations that may be associated with the direct effects of some antipsychotics on lipid levels". Schizophr. Res. 98 (1–3): 40–6. doi:10.1016/j.schres.2007.10.003. PMID 18031993.
- Kreuz S, Schoelch C, Thomas L, et al. (2009). "Acetyl-CoA carboxylases 1 and 2 show distinct expression patterns in rats and humans and alterations in obesity and diabetes". Diabetes Metab. Res. Rev. 25 (6): 577–86. doi:10.1002/dmrr.997. PMID 19618481.
- Castle JC, Hara Y, Raymond CK, et al. (2009). Zanger, Ulrich. ed. "ACC2 is expressed at high levels in human white adipose and has an isoform with a novel N-terminus [corrected"]. PLoS ONE 4 (2): e4369. doi:10.1371/journal.pone.0004369. PMC 2629817. PMID 19190759. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2629817.
- Højlund K, Mustard KJ, Staehr P, et al. (2004). "AMPK activity and isoform protein expression are similar in muscle of obese subjects with and without type 2 diabetes". Am. J. Physiol. Endocrinol. Metab. 286 (2): E239–44. doi:10.1152/ajpendo.00326.2003. PMID 14532170.
- Barbe L, Lundberg E, Oksvold P, et al. (2008). "Toward a confocal subcellular atlas of the human proteome". Mol. Cell Proteomics 7 (3): 499–508. doi:10.1074/mcp.M700325-MCP200. PMID 18029348.
- Szabo de Edelenyi F, Goumidi L, Bertrais S, et al. (2008). "Prediction of the metabolic syndrome status based on dietary and genetic parameters, using Random Forest". Genes & nutrition 3 (3–4): 173–6. doi:10.1007/s12263-008-0097-y. PMC 2593021. PMID 19034549. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2593021.
- Conde E, Suarez-Gauthier A, García-García E, et al. (2007). "Specific pattern of LKB1 and phospho-acetyl-CoA carboxylase protein immunostaining in human normal tissues and lung carcinomas". Hum. Pathol. 38 (9): 1351–60. doi:10.1016/j.humpath.2007.01.022. PMID 17521700.
- Rosa G, Manco M, Vega N, et al. (2003). "Decreased muscle acetyl-coenzyme A carboxylase 2 mRNA and insulin resistance in formerly obese subjects". Obes. Res. 11 (11): 1306–12. doi:10.1038/oby.2003.177. PMID 14627750.
- Oh SY, Lee MY, Kim JM, et al. (2005). "Alternative usages of multiple promoters of the acetyl-CoA carboxylase beta gene are related to differential transcriptional regulation in human and rodent tissues". J. Biol. Chem. 280 (7): 5909–16. doi:10.1074/jbc.M409037200. PMID 15590647.
- Locke GA, Cheng D, Witmer MR, et al. (2008). "Differential activation of recombinant human acetyl-CoA carboxylases 1 and 2 by citrate". Arch. Biochem. Biophys. 475 (1): 72–9. doi:10.1016/j.abb.2008.04.011. PMID 18455495.
- Cho YS, Lee JI, Shin D, et al. (2010). "Molecular mechanism for the regulation of human ACC2 through phosphorylation by AMPK". Biochem. Biophys. Res. Commun. 391 (1): 187–92. doi:10.1016/j.bbrc.2009.11.029. PMID 19900410.
- Strausberg RL, Feingold EA, Grouse LH, et al. (2002). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=139241.
- Frøsig C, Jørgensen SB, Hardie DG, et al. (2004). "5'-AMP-activated protein kinase activity and protein expression are regulated by endurance training in human skeletal muscle". Am. J. Physiol. Endocrinol. Metab. 286 (3): E411–7. doi:10.1152/ajpendo.00317.2003. PMID 14613924.
- Ruaño G, Bernene J, Windemuth A, et al. (2009). "Physiogenomic comparison of edema and BMI in patients receiving rosiglitazone or pioglitazone". Clin. Chim. Acta 400 (1–2): 48–55. doi:10.1016/j.cca.2008.10.009. PMID 18996102.
- Kim KW, Yamane H, Zondlo J, et al. (2007). "Expression, purification, and characterization of human acetyl-CoA carboxylase 2". Protein Expr. Purif. 53 (1): 16–23. doi:10.1016/j.pep.2006.11.021. PMID 17223360.
- Ruderman N, Prentki M (2004). "AMP kinase and malonyl-CoA: targets for therapy of the metabolic syndrome". Nat Rev Drug Discov 3 (4): 340–51. doi:10.1038/nrd1344. PMID 15060529.