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CYP4A11  -  cytochrome P450, family 4, subfamily A,...

Homo sapiens

Synonyms: 20-HETE synthase, 20-hydroxyeicosatetraenoic acid synthase, CP4Y, CYP4A2, CYP4AII, ...
 
 
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Disease relevance of CYP4A11

  • The recombinant CYP4A11 protein expressed in Escherichia coli using the pCWOri expression vector was purified to an almost electrophoretically homogeneous state with a specific content of 6.4 nmol of P450/mg of protein [1].
  • Reduced CYP4A11 apoprotein levels were found in chronic hepatitis samples and in liver samples showing fatty changes [2].
  • We studied the effects of retinoids on the regulation of CYP4A11 in the human hepatoma cell line HepaRG [3].
  • These observations suggest the potential for involvement of Cd as a mediator of CYP4A11 expression in kidney cortex and indicate that elevations in kidney Cd content may be involved in hypertension via alteration of the expression of this particular isoform [4].
 

High impact information on CYP4A11

 

Chemical compound and disease context of CYP4A11

 

Biological context of CYP4A11

  • 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 [7].
  • The purified enzyme (7.4 nmol P450/mg protein) had an NH2-terminal amino acid sequence identical to that predicted from the human CYP4A11 cDNA over the first 20 residues found [10].
  • A second variant form of CYP4A11 cDNA, designated CYP4A11v, was isolated from the same library and had a deletion of a single adenine residue, thereby extending the reading frame and resulting in a protein of 591 amino acids [11].
  • The CYP4A11 gene spanned 12,568 bp and contained 12 exons [1].
  • The assignment of the human CYP4A11 gene to chromosome 1 was confirmed by somatic cell hybridization [12].
 

Anatomical context of CYP4A11

 

Associations of CYP4A11 with chemical compounds

  • CYP4A11 had little catalytic activity for the metabolism of 17beta-estradiol and estrone [14].
  • Although (omega-1)- and (omega)-hydroxylation of fatty acids is attributed to CYP2E1 and CYP4A11, respectively, in the liver or kidney, no omega-hydroxylation of lauric acid was observed in microsomal preparations from cultured keratinocytes [13].
  • Furthermore, a strong correlation (r = 0.89; P < 0.001) was found between immunochemically determined CYP4A11 content and laurate omega-hydroxylase activity in liver samples from 11 different subjects [10].
  • Baculovirus-mediated cDNA expression of CYP4A11 yielded a P450 protein having a lambda max of 452 nm when reduced and complexed with carbon monoxide [11].
  • Metabolism of arachidonic acid to 20-hydroxy-5,8,11, 14-eicosatetraenoic acid by P450 enzymes in human liver: involvement of CYP4F2 and CYP4A11 [15].
 

Regulatory relationships of CYP4A11

  • Quantitative real-time PCR determined that CYP4A22 mRNA is expressed at significantly lower levels than CYP4A11 mRNA in human liver samples [16].
 

Other interactions of CYP4A11

  • Our results demonstrate that CYP4F2 and CYP4A11 underlie conversion of AA to 20-HETE, a natriuretic and vasoactive eicosanoid, in human kidney [7].
  • In addition, the reduction samples contained CYP4A11 and CYP2D6 [17].
  • The cDNA-deduced amino acid sequence encoded a protein of 519 amino acids that was designated CYP4A11 (Nelson et al., 1993) and exhibited 76%, 72%, 80%, and 53% similarities to rat CYP4A1, rat CYP4A3, rabbit CYP4A6, and human CYP4B1, respectively [11].
  • Analysis of the laurate omega-hydroxylation reaction in human liver microsomes revealed kinetic parameters (a lone Km of 48.9 microM with a VMAX of 3.72 nmol 12-hydroxylaurate formed/min/nmol P450) consistent with catalysis by CYP4A11 [10].
  • Except for CYP4A11, the levels of individual CYP mRNA were higher in varicose veins than in control veins [18].
 

Analytical, diagnostic and therapeutic context of CYP4A11

References

  1. Human fatty acid omega-hydroxylase, CYP4A11: determination of complete genomic sequence and characterization of purified recombinant protein. Kawashima, H., Naganuma, T., Kusunose, E., Kono, T., Yasumoto, R., Sugimura, K., Kishimoto, T. Arch. Biochem. Biophys. (2000) [Pubmed]
  2. Associations between human liver and kidney cadmium content and immunochemically detected CYP4A11 apoprotein. Baker, J.R., Satarug, S., Urbenjapol, S., Edwards, R.J., Williams, D.J., Moore, M.R., Reilly, P.E. Biochem. Pharmacol. (2002) [Pubmed]
  3. CYP4A11 is repressed by retinoic acid in human liver cells. Antoun, J., Amet, Y., Simon, B., Dréano, Y., Corlu, A., Corcos, L., Salaun, J.P., Plée-Gautier, E. FEBS Lett. (2006) [Pubmed]
  4. Potential for early involvement of CYP isoforms in aspects of human cadmium toxicity. Baker, J.R., Satarug, S., Edwards, R.J., Moore, M.R., Williams, D.J., Reilly, P.E. Toxicol. Lett. (2003) [Pubmed]
  5. Autocatalytic mechanism and consequences of covalent heme attachment in the cytochrome P4504A family. LeBrun, L.A., Hoch, U., Ortiz de Montellano, P.R. J. Biol. Chem. (2002) [Pubmed]
  6. Inhibitory cross-talk between STAT5b and liver nuclear factor HNF3beta: impact on the regulation of growth hormone pulse-stimulated, male-specific liver cytochrome P-450 gene expression. Park, S.H., Waxman, D.J. J. Biol. Chem. (2001) [Pubmed]
  7. 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]
  8. The catalytic site of cytochrome P4504A11 (CYP4A11) and its L131F mutant. Dierks, E.A., Zhang, Z., Johnson, E.F., de Montellano, P.R. J. Biol. Chem. (1998) [Pubmed]
  9. Association of the T8590C polymorphism of CYP4A11 with hypertension in the MONICA Augsburg echocardiographic substudy. Mayer, B., Lieb, W., Götz, A., König, I.R., Aherrahrou, Z., Thiemig, A., Holmer, S., Hengstenberg, C., Doering, A., Loewel, H., Hense, H.W., Schunkert, H., Erdmann, J. Hypertension (2005) [Pubmed]
  10. Identification of CYP4A11 as the major lauric acid omega-hydroxylase in human liver microsomes. Powell, P.K., Wolf, I., Lasker, J.M. Arch. Biochem. Biophys. (1996) [Pubmed]
  11. Complete cDNA sequence and cDNA-directed expression of CYP4A11, a fatty acid omega-hydroxylase expressed in human kidney. Imaoka, S., Ogawa, H., Kimura, S., Gonzalez, F.J. DNA Cell Biol. (1993) [Pubmed]
  12. Species-specific induction of cytochrome P-450 4A RNAs: PCR cloning of partial guinea-pig, human and mouse CYP4A cDNAs. Bell, D.R., Plant, N.J., Rider, C.G., Na, L., Brown, S., Ateitalla, I., Acharya, S.K., Davies, M.H., Elias, E., Jenkins, N.A. Biochem. J. (1993) [Pubmed]
  13. Cytochrome P450 4A11 expression in human keratinocytes: effects of ultraviolet irradiation. Gonzalez, M.C., Marteau, C., Franchi, J., Migliore-Samour, D. Br. J. Dermatol. (2001) [Pubmed]
  14. Characterization of the oxidative metabolites of 17beta-estradiol and estrone formed by 15 selectively expressed human cytochrome p450 isoforms. Lee, A.J., Cai, M.X., Thomas, P.E., Conney, A.H., Zhu, B.T. Endocrinology (2003) [Pubmed]
  15. 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]
  16. Differential regulation of human CYP4A genes by peroxisome proliferators and dexamethasone. Savas, U., Hsu, M.H., Johnson, E.F. Arch. Biochem. Biophys. (2003) [Pubmed]
  17. Characterization of cytochrome P450 enzymes in human breast tissue from reduction mammaplasties. Hellmold, H., Rylander, T., Magnusson, M., Reihnér, E., Warner, M., Gustafsson, J.A. J. Clin. Endocrinol. Metab. (1998) [Pubmed]
  18. Cytochromes P450 are differently expressed in normal and varicose human saphenous veins: linkage with varicosis. Bertrand-Thiebault, C., Ferrari, L., Boutherin-Falson, O., Kockx, M., Desquand-Billiald, S., Fichelle, J.M., Nottin, R., Renaud, J.F., Batt, A.M., Visvikis, S. Clin. Exp. Pharmacol. Physiol. (2004) [Pubmed]
  19. Expression of glutathione-dependent enzymes and cytochrome P450s in freshly isolated and primary cultures of proximal tubular cells from human kidney. Cummings, B.S., Lasker, J.M., Lash, L.H. J. Pharmacol. Exp. Ther. (2000) [Pubmed]
  20. Characterization of the CYP4A11 gene, a second CYP4A gene in humans. Bellamine, A., Wang, Y., Waterman, M.R., Gainer, J.V., Dawson, E.P., Brown, N.J., Capdevila, J.H. Arch. Biochem. Biophys. (2003) [Pubmed]
 
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