CYP4F2

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Identifiers
Aliases
External IDsGeneCards: [1]
Orthologs
SpeciesHumanMouse
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Leukotriene-B(4) omega-hydroxylase 1 is an enzyme that in humans is encoded by the CYP4F2 gene.[1][2][3]

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.[3]

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.[4] 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).,[5][6][7][7][8][6][7][9][9][10][11][12][13]

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.[14][15] This hydroxylation-induced inactivation may underlie the proposed roles of the cytochromes in dampening inflammatory responses and the reported associations of certain CYP4F2 single nucleotide variants (SNPs) with human Crohn's disease (rs2108622)[16] and Coeliac disease (rs3093156 and rs3093156).[17][18][19][20][21]

References

  1. ↑ Chen L, Hardwick JP (Jan 1993). "Identification of a new P450 subfamily, CYP4F1, expressed in rat hepatic tumors". Archives of Biochemistry and Biophysics. 300 (1): 18–23. doi:10.1006/abbi.1993.1003. PMID 8424651.
  2. ↑ Kikuta Y, Kusunose E, Kondo T, Yamamoto S, Kinoshita H, Kusunose M (Jul 1994). "Cloning and expression of a novel form of leukotriene B4 omega-hydroxylase from human liver". FEBS Letters. 348 (1): 70–4. doi:10.1016/0014-5793(94)00587-7. PMID 8026587.
  3. ↑ 3.0 3.1 "Entrez Gene: CYP4F2 cytochrome P450, family 4, subfamily F, polypeptide 2".
  4. ↑ Hoopes SL, Garcia V, Edin ML, Schwartzman ML, Zeldin DC (Jul 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.
  5. ↑ Ward, N. C.; Tsai, I. J.; Barden, A; Van Bockxmeer, F. M.; Puddey, I. B.; Hodgson, J. M.; Croft, K. D. (2008). "A single nucleotide polymorphism in the CYP4F2 but not CYP4A11 gene is associated with increased 20-HETE excretion and blood pressure". Hypertension. 51 (5): 1393–8. doi:10.1161/HYPERTENSIONAHA.107.104463. PMID 18391101.
  6. ↑ 6.0 6.1 Fava, C; Montagnana, M; Almgren, P; Rosberg, L; Lippi, G; Hedblad, B; Engström, G; Berglund, G; Minuz, P; Melander, O (2008). "The V433M variant of the CYP4F2 is associated with ischemic stroke in male Swedes beyond its effect on blood pressure". Hypertension. 52 (2): 373–80. doi:10.1161/HYPERTENSIONAHA.108.114199. PMID 18574070.
  7. ↑ 7.0 7.1 7.2 Munshi, A; Sharma, V; Kaul, S; Al-Hazzani, A; Alshatwi, A. A.; Shafi, G; Koppula, R; Mallemoggala, S. B.; Jyothy, A (2012). "Association of 1347 G/A cytochrome P450 4F2 (CYP4F2) gene variant with hypertension and stroke". Molecular Biology Reports. 39 (2): 1677–82. doi:10.1007/s11033-011-0907-y. PMID 21625857.
  8. ↑ Fu, Z; Nakayama, T; Sato, N; Izumi, Y; Kasamaki, Y; Shindo, A; Ohta, M; Soma, M; Aoi, N; Sato, M; Matsumoto, K; Ozawa, Y; Ma, Y (2008). "Haplotype-based case-control study of the human CYP4F2 gene and essential hypertension in Japanese subjects". Hypertension Research. 31 (9): 1719–26. doi:10.1291/hypres.31.1719. PMID 18971550.
  9. ↑ 9.0 9.1 Fu, Z; Nakayama, T; Sato, N; Izumi, Y; Kasamaki, Y; Shindo, A; Ohta, M; Soma, M; Aoi, N; Sato, M; Matsumoto, K; Ozawa, Y; Ma, Y (2008). "A haplotype of the CYP4F2 gene is associated with cerebral infarction in Japanese men". American Journal of Hypertension. 21 (11): 1216–23. doi:10.1038/ajh.2008.276. PMID 18787519.
  10. ↑ Ward, N. C.; Croft, K. D.; Puddey, I. B.; Phillips, M; Van Bockxmeer, F; Beilin, L. J.; Barden, A. E. (2014). "The effect of a single nucleotide polymorphism of the CYP4F2 gene on blood pressure and 20-hydroxyeicosatetraenoic acid excretion after weight loss". Journal of Hypertension. 32 (7): 1495–502, discussion 1502. doi:10.1097/HJH.0000000000000208. PMID 24984178.
  11. ↑ Ding, H; Cui, G; Zhang, L; Xu, Y; Bao, X; Tu, Y; Wu, B; Wang, Q; Hui, R; Wang, W; Dackor, R. T.; Kissling, G. E.; Zeldin, D. C.; Wang, D. W. (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.
  12. ↑ Fu, Z; Nakayama, T; Sato, N; Izumi, Y; Kasamaki, Y; Shindo, A; Ohta, M; Soma, M; Aoi, N; Sato, M; Ozawa, Y; Ma, Y; Matsumoto, K; Doba, N; Hinohara, S (2009). "A haplotype of the CYP4F2 gene associated with myocardial infarction in Japanese men". Molecular Genetics and Metabolism. 96 (3): 145–7. doi:10.1016/j.ymgme.2008.11.161. PMID 19097922.
  13. ↑ Stec, D. E.; Roman, R. J.; Flasch, A; Rieder, M. J. (2007). "Functional polymorphism in human CYP4F2 decreases 20-HETE production". Physiological Genomics. 30 (1): 74–81. doi:10.1152/physiolgenomics.00003.2007. PMID 17341693.
  14. ↑ Kikuta, Y; Kusunose, E; Sumimoto, H; Mizukami, Y; Takeshige, K; Sakaki, T; Yabusaki, Y; Kusunose, M (1998). "Purification and characterization of recombinant human neutrophil leukotriene B4 omega-hydroxylase (cytochrome P450 4F3)". Archives of Biochemistry and Biophysics. 355 (2): 201–5. doi:10.1006/abbi.1998.0724. PMID 9675028.
  15. ↑ Hardwick, J. P. (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.
  16. ↑ http://www.snpedia.com/index.php/Rs2108622
  17. ↑ Curley, C. R.; Monsuur, A. J.; Wapenaar, M. C.; Rioux, J. D.; Wijmenga, C (2006). "A functional candidate screen for coeliac disease genes". European Journal of Human Genetics. 14 (11): 1215–22. doi:10.1038/sj.ejhg.5201687. PMID 16835590.
  18. ↑ Corcos, L; Lucas, D; Le Jossic-Corcos, C; Dréano, Y; Simon, B; Plée-Gautier, E; Amet, Y; Salaün, J. P. (2012). "Human cytochrome P450 4F3: Structure, functions, and prospects". Drug Metabolism and Drug Interactions. 27 (2): 63–71. doi:10.1515/dmdi-2011-0037. PMID 22706230.
  19. ↑ Costea, I; Mack, D. R.; Lemaitre, R. N.; Israel, D; Marcil, V; Ahmad, A; Amre, D. K. (2014). "Interactions between the dietary polyunsaturated fatty acid ratio and genetic factors determine susceptibility to pediatric Crohn's disease". Gastroenterology. 146 (4): 929–31. doi:10.1053/j.gastro.2013.12.034. PMID 24406470.
  20. ↑ Costea, I; Mack, D. R.; Israel, D; Morgan, K; Krupoves, A; Seidman, E; Deslandres, C; Lambrette, P; Grimard, G; Levy, E; Amre, D. K. (2010). "Genes involved in the metabolism of poly-unsaturated fatty-acids (PUFA) and risk for Crohn's disease in children & young adults". PLoS ONE. 5 (12): e15672. doi:10.1371/journal.pone.0015672. PMC 3004960. PMID 21187935.
  21. ↑ Hardwick, J. P. (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.

Further reading

  • Simpson AE (Mar 1997). "The cytochrome P450 4 (CYP4) family". General Pharmacology. 28 (3): 351–9. doi:10.1016/S0306-3623(96)00246-7. PMID 9068972.
  • Powell PK, Wolf I, Jin R, Lasker JM (Jun 1998). "Metabolism of arachidonic acid to 20-hydroxy-5,8,11, 14-eicosatetraenoic acid by P450 enzymes in human liver: involvement of CYP4F2 and CYP4A11". The Journal of Pharmacology and Experimental Therapeutics. 285 (3): 1327–36. PMID 9618440.
  • Kikuta Y, Miyauchi Y, Kusunose E, Kusunose M (Sep 1999). "Expression and molecular cloning of human liver leukotriene B4 omega-hydroxylase (CYP4F2) gene". DNA and Cell Biology. 18 (9): 723–30. doi:10.1089/104454999315006. PMID 10492403.
  • Lasker JM, Chen WB, Wolf I, Bloswick BP, Wilson PD, Powell PK (Feb 2000). "Formation of 20-hydroxyeicosatetraenoic acid, a vasoactive and natriuretic eicosanoid, in human kidney. Role of Cyp4F2 and Cyp4A11". The Journal of Biological Chemistry. 275 (6): 4118–26. doi:10.1074/jbc.275.6.4118. PMID 10660572.
  • Zhang X, Chen L, Hardwick JP (Jun 2000). "Promoter activity and regulation of the CYP4F2 leukotriene B(4) omega-hydroxylase gene by peroxisomal proliferators and retinoic acid in HepG2 cells". Archives of Biochemistry and Biophysics. 378 (2): 364–76. doi:10.1006/abbi.2000.1836. PMID 10860554.
  • Zhang X, Hardwick JP (Dec 2000). "Regulation of CYP4F2 leukotriene B4 omega-hydroxylase by retinoic acids in HepG2 cells". Biochemical and Biophysical Research Communications. 279 (3): 864–71. doi:10.1006/bbrc.2000.4020. PMID 11162441.
  • Peng X, Pan X, Kenga M (Nov 1999). "[Isolation and sequencing of a novel form of cytochrome p-450 4F family from human liver]". Zhonghua Yi Xue Za Zhi. 79 (11): 860–2. PMID 11715494.
  • Nagata T, Takahashi Y, Ishii Y, Asai S, Sugahara M, Nishida Y, Murata A, Chin M, Schichino H, Koshinaga T, Fukuzawa M, Mugishima H (Jun 2003). "Profiling of genes differentially expressed between fetal liver and postnatal liver using high-density oligonucleotide DNA array". International Journal of Molecular Medicine. 11 (6): 713–21. doi:10.3892/ijmm.11.6.713. PMID 12736711.
  • Hsu MH, Savas U, Griffin KJ, Johnson EF (Feb 2007). "Regulation of human cytochrome P450 4F2 expression by sterol regulatory element-binding protein and lovastatin". The Journal of Biological Chemistry. 282 (8): 5225–36. doi:10.1074/jbc.M608176200. PMID 17142457.
  • Sontag TJ, Parker RS (May 2007). "Influence of major structural features of tocopherols and tocotrienols on their omega-oxidation by tocopherol-omega-hydroxylase". Journal of Lipid Research. 48 (5): 1090–8. doi:10.1194/jlr.M600514-JLR200. PMID 17284776.
  • Stec DE, Roman RJ, Flasch A, Rieder MJ (Jun 2007). "Functional polymorphism in human CYP4F2 decreases 20-HETE production". Physiological Genomics. 30 (1): 74–81. doi:10.1152/physiolgenomics.00003.2007. PMID 17341693.
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