ACACB explained

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

Further reading

• Cheng D, Chu CH, Chen L, Feder JN, Mintier GA, Wu Y, Cook JW, Harpel MR, Locke GA, An Y, Tamura JK . Expression, purification, and characterization of human and rat acetyl coenzyme A carboxylase (ACC) isozymes . Protein Expression and Purification . 51 . 1 . 11–21 . January 2007 . 16854592 . 10.1016/j.pep.2006.06.005 .
• Diaz FJ, Meary A, Arranz MJ, Ruaño G, Windemuth A, de Leon J . Acetyl-coenzyme A carboxylase alpha gene variations may be associated with the direct effects of some antipsychotics on triglyceride levels . Schizophrenia Research . 115 . 2–3 . 136–40 . December 2009 . 19846279 . 2784140 . 10.1016/j.schres.2009.09.038 .
• Madauss KP, Burkhart WA, Consler TG, Cowan DJ, Gottschalk WK, Miller AB, Short SA, Tran TB, Williams SP . The human ACC2 CT-domain C-terminus is required for full functionality and has a novel twist . Acta Crystallographica Section D . 65 . Pt 5 . 449–61 . May 2009 . 19390150 . 2725780 . 10.1107/S0907444909008014 . 2009AcCrD..65..449M .
• Kahn BB, Alquier T, Carling D, Hardie DG . AMP-activated protein kinase: ancient energy gauge provides clues to modern understanding of metabolism . Cell Metabolism . 1 . 1 . 15–25 . January 2005 . 16054041 . 10.1016/j.cmet.2004.12.003 . free .
• de Leon J, Correa JC, Ruaño G, Windemuth A, Arranz MJ, Diaz FJ . Exploring genetic variations that may be associated with the direct effects of some antipsychotics on lipid levels . Schizophrenia Research . 98 . 1–3 . 40–6 . January 2008 . 18031993 . 10.1016/j.schres.2007.10.003 . 26681612 .
• Kreuz S, Schoelch C, Thomas L, Rist W, Rippmann JF, Neubauer H . 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 . September 2009 . 19618481 . 10.1002/dmrr.997 . 33291872 .
• Castle JC, Hara Y, Raymond CK, Garrett-Engele P, Ohwaki K, Kan Z, Kusunoki J, Johnson JM . 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 . 2009 . 19190759 . 2629817 . 10.1371/journal.pone.0004369 . Zanger . Ulrich . free .
• Højlund K, Mustard KJ, Staehr P, Hardie DG, Beck-Nielsen H, Richter EA, Wojtaszewski JF . 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 . February 2004 . 14532170 . 10.1152/ajpendo.00326.2003 .
• Barbe L, Lundberg E, Oksvold P, Stenius A, Lewin E, Björling E, Asplund A, Pontén F, Brismar H, Uhlén M, Andersson-Svahn H . Toward a confocal subcellular atlas of the human proteome . Molecular & Cellular Proteomics . 7 . 3 . 499–508 . March 2008 . 18029348 . 10.1074/mcp.M700325-MCP200 . free .
• Szabo de Edelenyi F, Goumidi L, Bertrais S, Phillips C, Macmanus R, Roche H, Planells R, Lairon D . Prediction of the metabolic syndrome status based on dietary and genetic parameters, using Random Forest . Genes & Nutrition . 3 . 3–4 . 173–6 . December 2008 . 19034549 . 2593021 . 10.1007/s12263-008-0097-y .
• 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 . Specific pattern of LKB1 and phospho-acetyl-CoA carboxylase protein immunostaining in human normal tissues and lung carcinomas . Human Pathology . 38 . 9 . 1351–60 . September 2007 . 17521700 . 10.1016/j.humpath.2007.01.022 .
• Rosa G, Manco M, Vega N, Greco AV, Castagneto M, Vidal H, Mingrone G . Decreased muscle acetyl-coenzyme A carboxylase 2 mRNA and insulin resistance in formerly obese subjects . Obesity Research . 11 . 11 . 1306–12 . November 2003 . 14627750 . 10.1038/oby.2003.177 . free .
• Oh SY, Lee MY, Kim JM, Yoon S, Shin S, Park YN, Ahn YH, Kim KS . 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 . February 2005 . 15590647 . 10.1074/jbc.M409037200 . free .
• Locke GA, Cheng D, Witmer MR, Tamura JK, Haque T, Carney RF, Rendina AR, Marcinkeviciene J . Differential activation of recombinant human acetyl-CoA carboxylases 1 and 2 by citrate . Archives of Biochemistry and Biophysics . 475 . 1 . 72–9 . July 2008 . 18455495 . 10.1016/j.abb.2008.04.011 .
• Cho YS, Lee JI, Shin D, Kim HT, Jung HY, Lee TG, Kang LW, Ahn YJ, Cho HS, Heo YS . Molecular mechanism for the regulation of human ACC2 through phosphorylation by AMPK . Biochemical and Biophysical Research Communications . 391 . 1 . 187–92 . January 2010 . 19900410 . 10.1016/j.bbrc.2009.11.029 .
• Frøsig C, Jørgensen SB, Hardie DG, Richter EA, Wojtaszewski JF . 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 . March 2004 . 14613924 . 10.1152/ajpendo.00317.2003 .
• Ruaño G, Bernene J, Windemuth A, Bower B, Wencker D, Seip RL, Kocherla M, Holford TR, Petit WA, Hanks S . 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 . February 2009 . 18996102 . 10.1016/j.cca.2008.10.009 .
• Kim KW, Yamane H, Zondlo J, Busby J, Wang M . Expression, purification, and characterization of human acetyl-CoA carboxylase 2 . Protein Expression and Purification . 53 . 1 . 16–23 . May 2007 . 17223360 . 10.1016/j.pep.2006.11.021 .
• Ruderman N, Prentki M . AMP kinase and malonyl-CoA: targets for therapy of the metabolic syndrome . Nature Reviews. Drug Discovery . 3 . 4 . 340–51 . April 2004 . 15060529 . 10.1038/nrd1344 . 36977305 .

Notes and References

1. Web site: Entrez Gene: acetyl-Coenzyme A carboxylase beta.
2. 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 . Identification of a second human acetyl-CoA carboxylase gene . The Biochemical Journal . 316 (Pt 3) . 3 . 915–22 . June 1996 . 8670171 . 1217437 . 10.1042/bj3160915.
3. Corbett JW, Harwood JH . Inhibitors of mammalian acetyl-CoA carboxylase . Recent Patents on Cardiovascular Drug Discovery . 2 . 3 . 162–80 . November 2007 . 18221116 . 10.2174/157489007782418928 .
4. Olson DP, Pulinilkunnil T, Cline GW, Shulman GI, Lowell BB . Gene knockout of Acc2 has little effect on body weight, fat mass, or food intake . Proceedings of the National Academy of Sciences of the United States of America . 107 . 16 . 7598–603 . April 2010 . 20368432 . 2867727 . 10.1073/pnas.0913492107 . 2010PNAS..107.7598O . free .