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CYP4F2
Leukotriene-B(4) omega-hydroxylase 1 is an enzyme that in humans is encoded by the ''CYP4F2'' gene.〔(【引用サイトリンク】 url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=8529 )〕
== Function ==
This gene encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids, fatty acids, and other lipids. This protein localizes to the endoplasmic reticulum. The enzyme starts the process of inactivating and degrading leukotriene B4, a potent mediator of inflammation. This gene is part of a cluster of cytochrome P450 genes on chromosome 19. Another member of this family, CYP4F11, is approximately 16 kb away.〔
CYP4F2 along with CYP4A22, CYP4A11, and CYP4F3 and CYP2U1 also metabolize arachidonic acid to 20-Hydroxyeicosatetraenoic acid (20-HETE) by an Omega oxidation reaction with the predominant 20-HETE-synthesizing enzymes in humans being CYP4F2 followed by CYP4A11; 20-HETE regulates blood flow, vascularization, blood pressure, and kidney tubule absorption of ions in rodents and possibly humans. Gene polymorphism variants of CYP4F2 are associated with the development of hypertension, cerebral infarction (i.e. ischemic stroke), and myocardial infarction in humans (see 20-Hydroxyeicosatetraenoic acid for details).,〔Hypertension. 2008 May;51(5):1393-8. doi: 10.1161/HYPERTENSIONAHA.107.104463.〕〔Hypertension. 2008 Aug;52(2):373-80. doi: 10.1161/HYPERTENSIONAHA.108.114199〕〔Mol Biol Rep. 2012 Feb;39(2):1677-82. doi: 10.1007/s11033-011-0907-y>〕〔Hypertens Res. 2008 Sep;31(9):1719-26. doi: 10.1291/hypres.31.1719〕〔J Hypertens. 2014 Jul;32(7):1495-502; discussion 1502. doi: 10.1097/HJH.0000000000000208〕〔Am J Hypertens. 2008 Nov;21(11):1216-23. doi: 10.1038/ajh.2008.276〕〔Mol Biol Rep. 2012 Feb;39(2):1677-82. doi: 10.1007/s11033-011-0907-y〕〔〔〔Pharmacogenet Genomics. 2010 Mar;20(3):187-94. doi: 10.1097/FPC.0b013e328336eefe〕〔Mol Genet Metab. 2009 Mar;96(3):145-7. doi: 10.1016/j.ymgme.2008.11.161〕〔Physiol Genomics. 2007 Jun 19;30(1):74-81〕〔Am J Hypertens. 2008 Nov;21(11):1216-23. doi: 10.1038/ajh.2008.276.〕
Members of the CYP4A and CYP4F sub-families may also ω-hydroxylate and thereby reduce the activity of various fatty acid metabolites of arachidonic acid including LTB4, 5-HETE, 5-oxo-eicosatetraenoic acid, 12-HETE, and several prostaglandins that are involved in regulating various inflammatory, vascular, and other responses in animals and humans.〔Arch Biochem Biophys. 1998 Jul 15;355(2):201〕〔Biochem Pharmacol. 2008 Jun 15;75(12):2263-75. doi: 10.1016/j.bcp.2008.03.004〕 This hydroxylation-induced inactivation may underlie the proposed roles of the cytochromes in dampening inflammatory responses and the reported associations of certain CYP4F2 and CYP4F3 single nucleotide variants with human Krohn's disease and Coeliac disease, respectively.〔Eur J Hum Genet. 2006 Nov;14(11):1215-22〕〔Drug Metabol Drug Interact. 2012 Apr 19;27(2):63-71. doi: 10.1515/dmdi-2011-0037〕〔Gastroenterology. 2014 Apr;146(4):929-31. doi: 10.1053/j.gastro.2013.12.034〕
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