CYP4F11 (cytochrome P450, family 4, subfamily F, polypeptide 11) is a protein that in humans is encoded by the CYP4F11 gene.[5] 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 and other lipids. This gene is part of a cluster of cytochrome P450 genes on chromosome 19. Another member of this family, CYP4F2, is approximately 16 kb away. Alternatively spliced transcript variants encoding the same protein have been found for this gene.[6]
Expression
[edit]CYP4F11 is expressed in liver, kidney, heart, brain, and skeletal muscle and is overexpressed in ovarian and colon cancers; perhaps relativant to its overexpression in ovarian cancer, its gene has an estrogen receptor α responsive site in its Promoter (genetics) site.[7]
Activities and possible functions
[edit]CYP4F11 is active in metabolism of many drugs including benzphetamine, ethylmorphine, chlorpromazine, imipramine, and erythromycin;.[7]
The cytochrome is also able to hydroxylate short-chain and 3-hydroxylated medium chain fatty acids by attaching a hydroxyl residue to their terminal carbon by omega oxidation in a reaction that may be critical to the processing of these fatty acids.[8] It likewise omega-hydroxylates Vitamin Ks including menaquinone in a metabolic step which is essential for their further metabolism by beta oxidation and probably thereby their removal by catabolism to regulate their tissue levels.[8]
CYP4F11 omega-hydroxylates leukotriene B4 (LTB4) to 20-hydroxy-LTB4, 5-Hydroxyicosatetraenoic acid (5-HETE) to 20-hydroxy-5-HETE (i.e. 5,20-diHETE), 12-hydroxyeicosatetraenoic acid (12-HETE) to 12,20-diHETE, lipoxins and possibly 5-oxo-eicosatetraenoic acid (5-oxo-ETE) to their 20-hydroxy metabolites; these reactions begin the inactivation of these pro- (LTB4, 5-HETE, 12-HETE, and 5-oxo-ETE) and anti- (lipoxins) cell signaling agents; however, it is relatively weak compared to, and therefore possibly not as physiologically relevant as, other CYP4Fs such as CYP4F2, CYP4F3a, CYP4F3b, CYP4A11 and CYP4F2 in doing so.[7][8] The enzyme also hydroxylates arachidonic acid (i.e. eicosatetraenoic acid to 20-Hydroxyeicosatetraenoic acid) (20-HETE) although other cytochromes such as CYP4A11 and CYP4F2 appear more important in this metabolic conversion.[7] 20-HETE is a short-lived potent signaling agent that functions to regulate blood flow, vascularization, blood pressure, and kidney tubule absorption of ions in rodents and possibly humans.[9] Gene polymorphism variants of CYP4A11 are associated with the development of hypertension and cerebral infarction (i.e. ischemic stroke) in humans (see 20-Hydroxyeicosatetraenoic acid).[10][11][12][13][14][15] In spite of its relative impotency and/or importance in accomplishing these omega-hydroxylations, CYP4F11 may contribute to them in certain tissues.
Further reading
[edit]Johnson AL, Edson KZ, Totah RA, Rettie AE. Cytochrome P450 ω-Hydroxylases in Inflammation and Cancer. Adv. Pharmacol. 74:223-62, 2015.[8]
References
[edit]- ^ a b c GRCh38: Ensembl release 89: ENSG00000171903 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000090700 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ Cui X, Nelson DR, Strobel HW (September 2000). "A novel human cytochrome P450 4F isoform (CYP4F11): cDNA cloning, expression, and genomic structural characterization". Genomics. 68 (2): 161–6. doi:10.1006/geno.2000.6276. PMID 10964514.
- ^
This article incorporates public domain material from "Entrez Gene: CYP4F11". Reference Sequence collection. National Center for Biotechnology Information.
- ^ a b c d Hardwick JP (June 2008). "Cytochrome P450 omega hydroxylase (CYP4) function in fatty acid metabolism and metabolic diseases". Biochemical Pharmacology. 75 (12): 2263–75. doi:10.1016/j.bcp.2008.03.004. PMID 18433732.
- ^ a b c d Johnson AL, Edson KZ, Totah RA, Rettie AE (2015). "Cytochrome P450 ω-Hydroxylases in Inflammation and Cancer". Cytochrome P450 Function and Pharmacological Roles in Inflammation and Cancer. Advances in Pharmacology. Vol. 74. pp. 223–62. doi:10.1016/bs.apha.2015.05.002. ISBN 9780128031193. PMC 4667791. PMID 26233909.
- ^ Hoopes SL, Garcia V, Edin ML, Schwartzman ML, Zeldin DC (July 2015). "Vascular actions of 20-HETE". Prostaglandins & Other Lipid Mediators. 120: 9–16. doi:10.1016/j.prostaglandins.2015.03.002. PMC 4575602. PMID 25813407.
- ^ Gainer JV, Bellamine A, Dawson EP, Womble KE, Grant SW, Wang Y, Cupples LA, Guo CY, Demissie S, O'Donnell CJ, Brown NJ, Waterman MR, Capdevila JH (January 2005). "Functional variant of CYP4A11 20-hydroxyeicosatetraenoic acid synthase is associated with essential hypertension". Circulation. 111 (1): 63–9. CiteSeerX 10.1.1.335.1764. doi:10.1161/01.CIR.0000151309.82473.59. PMID 15611369.
- ^ Gainer JV, Lipkowitz MS, Yu C, Waterman MR, Dawson EP, Capdevila JH, Brown NJ (August 2008). "Association of a CYP4A11 variant and blood pressure in black men". Journal of the American Society of Nephrology. 19 (8): 1606–12. doi:10.1681/ASN.2008010063. PMC 2488260. PMID 18385420.
- ^ Fu Z, Nakayama T, Sato N, Izumi Y, Kasamaki Y, Shindo A, Ohta M, Soma M, Aoi N, Sato M, Ozawa Y, Ma Y (March 2008). "A haplotype of the CYP4A11 gene associated with essential hypertension in Japanese men". Journal of Hypertension. 26 (3): 453–61. doi:10.1097/HJH.0b013e3282f2f10c. PMID 18300855. S2CID 23680415.
- ^ Mayer B, Lieb W, Götz A, König IR, Aherrahrou Z, Thiemig A, Holmer S, Hengstenberg C, Doering A, Loewel H, Hense HW, Schunkert H, Erdmann J (October 2005). "Association of the T8590C polymorphism of CYP4A11 with hypertension in the MONICA Augsburg echocardiographic substudy". Hypertension. 46 (4): 766–71. doi:10.1161/01.HYP.0000182658.04299.15. PMID 16144986.
- ^ Sugimoto K, Akasaka H, Katsuya T, Node K, Fujisawa T, Shimaoka I, Yasuda O, Ohishi M, Ogihara T, Shimamoto K, Rakugi H (December 2008). "A polymorphism regulates CYP4A11 transcriptional activity and is associated with hypertension in a Japanese population". Hypertension. 52 (6): 1142–8. doi:10.1161/HYPERTENSIONAHA.108.114082. PMID 18936345.
- ^ Ding H, Cui G, Zhang L, Xu Y, Bao X, Tu Y, Wu B, Wang Q, Hui R, Wang W, Dackor RT, Kissling GE, Zeldin DC, Wang DW (March 2010). "Association of common variants of CYP4A11 and CYP4F2 with stroke in the Han Chinese population". Pharmacogenetics and Genomics. 20 (3): 187–94. doi:10.1097/FPC.0b013e328336eefe. PMC 3932492. PMID 20130494.
External links
[edit]- Human CYP4F11 genome location and CYP4F11 gene details page in the UCSC Genome Browser.
Further reading
[edit]- Dhar M, Sepkovic DW, Hirani V, Magnusson RP, Lasker JM (March 2008). "Omega oxidation of 3-hydroxy fatty acids by the human CYP4F gene subfamily enzyme CYP4F11". Journal of Lipid Research. 49 (3): 612–24. doi:10.1194/jlr.M700450-JLR200. PMID 18065749.
- Bonaldo MF, Lennon G, Soares MB (September 1996). "Normalization and subtraction: two approaches to facilitate gene discovery". Genome Research. 6 (9): 791–806. doi:10.1101/gr.6.9.791. PMID 8889548.
- Nelson DR, Zeldin DC, Hoffman SM, Maltais LJ, Wain HM, Nebert DW (January 2004). "Comparison of cytochrome P450 (CYP) genes from the mouse and human genomes, including nomenclature recommendations for genes, pseudogenes and alternative-splice variants". Pharmacogenetics. 14 (1): 1–18. doi:10.1097/00008571-200401000-00001. PMID 15128046.
- Simpson AE (March 1997). "The cytochrome P450 4 (CYP4) family". General Pharmacology. 28 (3): 351–9. doi:10.1016/S0306-3623(96)00246-7. PMID 9068972.
This article incorporates text from the United States National Library of Medicine, which is in the public domain.