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Gene Review

CYP4F2  -  cytochrome P450, family 4, subfamily F,...

Homo sapiens

Synonyms: 20-HETE synthase, 20-hydroxyeicosatetraenoic acid synthase, Arachidonic acid omega-hydroxylase, CYPIVF2, Cytochrome P450 4F2, ...
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Disease relevance of CYP4F2


High impact information on CYP4F2


Biological context of CYP4F2

  • Despite the monophasic nature of renal AA omega-hydroxylation kinetics, immunochemical studies revealed participation of two P450s, CYP4F2 and CYP4A11, since antibodies to these enzymes inhibited 20-HETE formation by 65 [5].
  • However, the human CYP4F2 gene was mapped to chromosome 19 [7].
  • The CYP4F2 gene contains at least 13 exons with its open reading frame being encoded from exon II to exon XIII [1].
  • The 5' flanking sequence downstream from -165 of the CYP4F2 gene has 75% similarity to the corresponding region of the CYP4F3 gene [1].
  • We sequenced a 6.7-kb genomic fragment of the human CYP4F2 gene that has the first five exons and 500 bp of the 5'-flanking region [8].

Anatomical context of CYP4F2

  • Among recombinant P450 enzymes, CYP4F2 and CYP4F3B catalyzed mainly the omega-hydroxylation of C18-epoxides with an apparent Vmax of between 0.84 and 15.0 min(-1), whereas the apparent Vmax displayed by CYP4F3A, the isoform found in leukocytes, ranged from 3.0 to 21.2 min(-1) [6].
  • Antibodies to CYP4F2 markedly inhibited (93.4 +/- 6%; n = 5) formation of 20-HETE by hepatic microsomes, whereas antibodies to CYP4A11 were much less inhibitory (13.0 +/- 9%; n = 5) [9].
  • CYP4F3 and CYP4F2 catalyse the inactivation of leukotriene B4 (LTB4), a potent mediator of inflammation responsible for recruitment and activation of neutrophils [10].
  • Peroxisome proliferators inhibit CYP4F2 gene promoter activity and cotransfection with PPARalpha or PPARalpha/RXRalpha can slightly attenuate this inhibition [8].
  • The expression of cytochrome P450 4F2 mRNAs was detected in HepG2 and A549 cells, and thus the arachidonic acid and leukotriene B(4) omega-hydroxylation activities in the nuclear envelope fractions of HepG2 and A549 cells are likely due to cytochrome P450 4F2 [11].

Associations of CYP4F2 with chemical compounds


Other interactions of CYP4F2


Analytical, diagnostic and therapeutic context of CYP4F2


  1. Expression and molecular cloning of human liver leukotriene B4 omega-hydroxylase (CYP4F2) gene. Kikuta, Y., Miyauchi, Y., Kusunose, E., Kusunose, M. DNA Cell Biol. (1999) [Pubmed]
  2. Mutations in a new cytochrome P450 gene in lamellar ichthyosis type 3. Lefèvre, C., Bouadjar, B., Ferrand, V., Tadini, G., Mégarbané, A., Lathrop, M., Prud'homme, J.F., Fischer, J. Hum. Mol. Genet. (2006) [Pubmed]
  3. {omega}-Oxidation of Very Long-chain Fatty Acids in Human Liver Microsomes: IMPLICATIONS FOR X-LINKED ADRENOLEUKODYSTROPHY. Sanders, R.J., Ofman, R., Duran, M., Kemp, S., Wanders, R.J. J. Biol. Chem. (2006) [Pubmed]
  4. Cytochrome P450 omega-hydroxylase pathway of tocopherol catabolism. Novel mechanism of regulation of vitamin E status. Sontag, T.J., Parker, R.S. J. Biol. Chem. (2002) [Pubmed]
  5. Formation of 20-hydroxyeicosatetraenoic acid, a vasoactive and natriuretic eicosanoid, in human kidney. Role of Cyp4F2 and Cyp4A11. Lasker, J.M., Chen, W.B., Wolf, I., Bloswick, B.P., Wilson, P.D., Powell, P.K. J. Biol. Chem. (2000) [Pubmed]
  6. Human CYP4F3s are the main catalysts in the oxidation of fatty acid epoxides. Le Quéré, V., Plée-Gautier, E., Potin, P., Madec, S., Salaün, J.P. J. Lipid Res. (2004) [Pubmed]
  7. A novel murine P-450 gene, Cyp4a14, is part of a cluster of Cyp4a and Cyp4b, but not of CYP4F, genes in mouse and humans. Heng, Y.M., Kuo, C.S., Jones, P.S., Savory, R., Schulz, R.M., Tomlinson, S.R., Gray, T.J., Bell, D.R. Biochem. J. (1997) [Pubmed]
  8. Promoter activity and regulation of the CYP4F2 leukotriene B(4) omega-hydroxylase gene by peroxisomal proliferators and retinoic acid in HepG2 cells. Zhang, X., Chen, L., Hardwick, J.P. Arch. Biochem. Biophys. (2000) [Pubmed]
  9. Metabolism of arachidonic acid to 20-hydroxy-5,8,11, 14-eicosatetraenoic acid by P450 enzymes in human liver: involvement of CYP4F2 and CYP4A11. Powell, P.K., Wolf, I., Jin, R., Lasker, J.M. J. Pharmacol. Exp. Ther. (1998) [Pubmed]
  10. A functional candidate screen for coeliac disease genes. Curley, C.R., Monsuur, A.J., Wapenaar, M.C., Rioux, J.D., Wijmenga, C. Eur. J. Hum. Genet. (2006) [Pubmed]
  11. omega-hydroxylation activity toward leukotriene B(4) and polyunsaturated fatty acids in the human hepatoblastoma cell line, HepG2, and human lung adenocarcinoma cell line, A549. Yamane, M., Abe, A. J. Biochem. (2000) [Pubmed]
  12. CYP4F Enzymes Are the Major Enzymes in Human Liver Microsomes That Catalyze the O-Demethylation of the Antiparasitic Prodrug DB289 [2,5-Bis(4-amidinophenyl)furan-bis-O-methylamidoxime]. Wang, M.Z., Saulter, J.Y., Usuki, E., Cheung, Y.L., Hall, M., Bridges, A.S., Loewen, G., Parkinson, O.T., Stephens, C.E., Allen, J.L., Zeldin, D.C., Boykin, D.W., Tidwell, R.R., Parkinson, A., Paine, M.F., Hall, J.E. Drug Metab. Dispos. (2006) [Pubmed]
  13. Gene expression of a novel cytochrome P450 of the CYP4F subfamily in human seminal vesicles. Bylund, J., Finnström, N., Oliw, E.H. Biochem. Biophys. Res. Commun. (1999) [Pubmed]
  14. A novel human cytochrome P450 4F isoform (CYP4F11): cDNA cloning, expression, and genomic structural characterization. Cui, X., Nelson, D.R., Strobel, H.W. Genomics (2000) [Pubmed]
  15. Vitamin E and drug metabolism. Brigelius-Flohé, R. Biochem. Biophys. Res. Commun. (2003) [Pubmed]
  16. Regulation of human cytochrome P450 4F2 expression by sterol regulatory element-binding protein and lovastatin. Hsu, M.H., Savas, U., Griffin, K.J., Johnson, E.F. J. Biol. Chem. (2007) [Pubmed]
  17. Renal and hepatic accumulation of cadmium and lead in the expression of CYP4F2 and CYP2E1. Baker, J.R., Edwards, R.J., Lasker, J.M., Moore, M.R., Satarug, S. Toxicol. Lett. (2005) [Pubmed]
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