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.
Cheng D, Chu CH, Chen L, Feder JN, Mintier GA, Wu Y, Cook JW, Harpel MR, Locke GA, An Y, Tamura JK (January 2007). "Expression, purification, and characterization of human and rat acetyl coenzyme A carboxylase (ACC) isozymes". Protein Expression and Purification. 51 (1): 11–21. doi:10.1016/j.pep.2006.06.005. PMID16854592.
Kahn BB, Alquier T, Carling D, Hardie DG (January 2005). "AMP-activated protein kinase: ancient energy gauge provides clues to modern understanding of metabolism". Cell Metabolism. 1 (1): 15–25. doi:10.1016/j.cmet.2004.12.003. PMID16054041.
de Leon J, Correa JC, Ruaño G, Windemuth A, Arranz MJ, Diaz FJ (January 2008). "Exploring genetic variations that may be associated with the direct effects of some antipsychotics on lipid levels". Schizophrenia Research. 98 (1–3): 40–6. doi:10.1016/j.schres.2007.10.003. PMID18031993.
Kreuz S, Schoelch C, Thomas L, Rist W, Rippmann JF, Neubauer H (September 2009). "Acetyl-CoA carboxylases 1 and 2 show distinct expression patterns in rats and humans and alterations in obesity and diabetes". Diabetes/Metabolism Research and Reviews. 25 (6): 577–86. doi:10.1002/dmrr.997. PMID19618481.
Højlund K, Mustard KJ, Staehr P, Hardie DG, Beck-Nielsen H, Richter EA, Wojtaszewski JF (February 2004). "AMPK activity and isoform protein expression are similar in muscle of obese subjects with and without type 2 diabetes". American Journal of Physiology. Endocrinology and Metabolism. 286 (2): E239–44. doi:10.1152/ajpendo.00326.2003. PMID14532170.
Barbe L, Lundberg E, Oksvold P, Stenius A, Lewin E, Björling E, Asplund A, Pontén F, Brismar H, Uhlén M, Andersson-Svahn H (March 2008). "Toward a confocal subcellular atlas of the human proteome". Molecular & Cellular Proteomics. 7 (3): 499–508. doi:10.1074/mcp.M700325-MCP200. PMID18029348.
Conde E, Suarez-Gauthier A, García-García E, Lopez-Rios F, Lopez-Encuentra A, García-Lujan R, Morente M, Sanchez-Verde L, Sanchez-Cespedes M (September 2007). "Specific pattern of LKB1 and phospho-acetyl-CoA carboxylase protein immunostaining in human normal tissues and lung carcinomas". Human Pathology. 38 (9): 1351–60. doi:10.1016/j.humpath.2007.01.022. PMID17521700.
Rosa G, Manco M, Vega N, Greco AV, Castagneto M, Vidal H, Mingrone G (November 2003). "Decreased muscle acetyl-coenzyme A carboxylase 2 mRNA and insulin resistance in formerly obese subjects". Obesity Research. 11 (11): 1306–12. doi:10.1038/oby.2003.177. PMID14627750.
Oh SY, Lee MY, Kim JM, Yoon S, Shin S, Park YN, Ahn YH, Kim KS (February 2005). "Alternative usages of multiple promoters of the acetyl-CoA carboxylase beta gene are related to differential transcriptional regulation in human and rodent tissues". The Journal of Biological Chemistry. 280 (7): 5909–16. doi:10.1074/jbc.M409037200. PMID15590647.
Locke GA, Cheng D, Witmer MR, Tamura JK, Haque T, Carney RF, Rendina AR, Marcinkeviciene J (July 2008). "Differential activation of recombinant human acetyl-CoA carboxylases 1 and 2 by citrate". Archives of Biochemistry and Biophysics. 475 (1): 72–9. doi:10.1016/j.abb.2008.04.011. PMID18455495.
Cho YS, Lee JI, Shin D, Kim HT, Jung HY, Lee TG, Kang LW, Ahn YJ, Cho HS, Heo YS (January 2010). "Molecular mechanism for the regulation of human ACC2 through phosphorylation by AMPK". Biochemical and Biophysical Research Communications. 391 (1): 187–92. doi:10.1016/j.bbrc.2009.11.029. PMID19900410.
Frøsig C, Jørgensen SB, Hardie DG, Richter EA, Wojtaszewski JF (March 2004). "5'-AMP-activated protein kinase activity and protein expression are regulated by endurance training in human skeletal muscle". American Journal of Physiology. Endocrinology and Metabolism. 286 (3): E411–7. doi:10.1152/ajpendo.00317.2003. PMID14613924.
Ruaño G, Bernene J, Windemuth A, Bower B, Wencker D, Seip RL, Kocherla M, Holford TR, Petit WA, Hanks S (February 2009). "Physiogenomic comparison of edema and BMI in patients receiving rosiglitazone or pioglitazone". Clinica Chimica Acta; International Journal of Clinical Chemistry. 400 (1–2): 48–55. doi:10.1016/j.cca.2008.10.009. PMID18996102.
Kim KW, Yamane H, Zondlo J, Busby J, Wang M (May 2007). "Expression, purification, and characterization of human acetyl-CoA carboxylase 2". Protein Expression and Purification. 53 (1): 16–23. doi:10.1016/j.pep.2006.11.021. PMID17223360.
Ruderman N, Prentki M (April 2004). "AMP kinase and malonyl-CoA: targets for therapy of the metabolic syndrome". Nature Reviews. Drug Discovery. 3 (4): 340–51. doi:10.1038/nrd1344. PMID15060529.