Biology:ACACB
Generic protein structure example |
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
- ↑ 1.0 1.1 "Entrez Gene: acetyl-Coenzyme A carboxylase beta". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=32.
- ↑ "Identification of a second human acetyl-CoA carboxylase gene". The Biochemical Journal 316 ( Pt 3) (3): 915–22. June 1996. doi:10.1042/bj3160915. PMID 8670171.
- ↑ "Inhibitors of mammalian acetyl-CoA carboxylase". Recent Patents on Cardiovascular Drug Discovery 2 (3): 162–80. November 2007. doi:10.2174/157489007782418928. PMID 18221116.
- ↑ "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. doi:10.1073/pnas.0913492107. PMID 20368432. Bibcode: 2010PNAS..107.7598O.
Further reading
- "Expression, purification, and characterization of human and rat acetyl coenzyme A carboxylase (ACC) isozymes". Protein Expression and Purification 51 (1): 11–21. January 2007. doi:10.1016/j.pep.2006.06.005. PMID 16854592.
- "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. doi:10.1016/j.schres.2009.09.038. PMID 19846279.
- "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. doi:10.1107/S0907444909008014. PMID 19390150. Bibcode: 2009AcCrD..65..449M.
- "AMP-activated protein kinase: ancient energy gauge provides clues to modern understanding of metabolism". Cell Metabolism 1 (1): 15–25. January 2005. doi:10.1016/j.cmet.2004.12.003. PMID 16054041.
- "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. doi:10.1016/j.schres.2007.10.003. PMID 18031993.
- "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. doi:10.1002/dmrr.997. PMID 19618481.
- Zanger, Ulrich, ed (2009). "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. PMID 19190759.
- "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. doi:10.1152/ajpendo.00326.2003. PMID 14532170.
- "Toward a confocal subcellular atlas of the human proteome". Molecular & Cellular Proteomics 7 (3): 499–508. March 2008. doi:10.1074/mcp.M700325-MCP200. PMID 18029348.
- "Prediction of the metabolic syndrome status based on dietary and genetic parameters, using Random Forest". Genes & Nutrition 3 (3–4): 173–6. December 2008. doi:10.1007/s12263-008-0097-y. PMID 19034549.
- "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. doi:10.1016/j.humpath.2007.01.022. PMID 17521700.
- "Decreased muscle acetyl-coenzyme A carboxylase 2 mRNA and insulin resistance in formerly obese subjects". Obesity Research 11 (11): 1306–12. November 2003. doi:10.1038/oby.2003.177. PMID 14627750.
- "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. doi:10.1074/jbc.M409037200. PMID 15590647.
- "Differential activation of recombinant human acetyl-CoA carboxylases 1 and 2 by citrate". Archives of Biochemistry and Biophysics 475 (1): 72–9. July 2008. doi:10.1016/j.abb.2008.04.011. PMID 18455495.
- "Molecular mechanism for the regulation of human ACC2 through phosphorylation by AMPK". Biochemical and Biophysical Research Communications 391 (1): 187–92. January 2010. doi:10.1016/j.bbrc.2009.11.029. PMID 19900410.
- "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. doi:10.1152/ajpendo.00317.2003. PMID 14613924.
- "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. doi:10.1016/j.cca.2008.10.009. PMID 18996102.
- "Expression, purification, and characterization of human acetyl-CoA carboxylase 2". Protein Expression and Purification 53 (1): 16–23. May 2007. doi:10.1016/j.pep.2006.11.021. PMID 17223360.
- "AMP kinase and malonyl-CoA: targets for therapy of the metabolic syndrome". Nature Reviews. Drug Discovery 3 (4): 340–51. April 2004. doi:10.1038/nrd1344. PMID 15060529.
External links
- Human ACACB genome location and ACACB gene details page in the UCSC Genome Browser.
Original source: https://en.wikipedia.org/wiki/ACACB.
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