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Gene Review

Cyp2a5  -  cytochrome P450, family 2, subfamily a,...

Mus musculus

Synonyms: CYPIIA5, Coh, Coumarin 7-hydroxylase, Cyp15a2, Cyp2a-5, ...
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Disease relevance of Cyp2a5


High impact information on Cyp2a5


Chemical compound and disease context of Cyp2a5


Biological context of Cyp2a5

  • Close linkage of the cytochrome P450IIA gene subfamily (Cyp2a) to Cyp2b and Coh on mouse chromosome 7 [8].
  • The theoretical pI values, determined from the amino acid sequence, were pI 9.91 for Cyp2a-4 and pI 10.01 for Cyp2a-5 [1].
  • Transfection experiments combined with mutation of the XRE site indicated that the site partly mediates the TCDD induction of Cyp2a5 [9].
  • Secondly, the coordinated up-regulation of the HO-1 and Cyp2a5 during Cd-mediated injury implicates a network of enzyme systems in the maintenance of balancing BR production and elimination [10].
  • The induction of Cyp2a5, QOR, and GSTYa catalytic activity and gene expression occurred primarily in kidney during or shortly after conditions of oxidant stress [11].

Anatomical context of Cyp2a5

  • Coumarin 7-hydroxylase activity was 20 pmol/mg/min. in mouse and 4 pmol/mg/min. in rat lung microsomes [12].
  • These results suggest that induction of Cyp2a5 that has been observed in mouse models of hepatitis and hepatoxicity may be related to oxidative injury to the endoplasmic reticulum of pericentral hepatocytes rather than exposure to pro-inflammatory cytokines [13].
  • Expression of type I and II in COS-1 cells revealed that the latter catalyzed coumarin 7-hydroxylase activity at 10 to approximately 14 pmol min-1 (mg of cellular protein)-1 [14].
  • Metyrapone clearly inhibited COH in mouse liver microsomes, but interestingly it had no effect on COH activity in human liver microsomes, although these two isozymes have earlier been shown to be immunologically similar [15].
  • From 100 G418-resistant clones initially isolated, three cell lines were chosen for further study based upon their morphologies, growth rates and CYP2A6-dependent coumarin 7-hydroxylase activities [16].

Associations of Cyp2a5 with chemical compounds

  • Together with previous reports [Aida & Negishi (1991) Biochemistry 30, 8041-8045], the current data suggest that both pyrazole and cobalt increase COH catalytic activity by affecting Cyp2a-5 by post-transcriptional mechanisms in mice [17].
  • Pyrazole, cobalt and phenobarbital increase the activity of coumarin 7-hydroxylase (COH) in mouse liver [17].
  • Three and 4 days after the cerium treatment, coinciding with the occurrence of overt liver damage, there was a dramatic decrease in COH activity [18].
  • Two days after the administration of a hepatotoxic dose of cerium chloride (2 mg/kg i.v.), COH activity was increased 3.2-fold in the liver of DBA/2 mice [18].
  • Anti-Cyp2a-5 antibody effectively inhibited mouse and rat lung coumarin 7-hydroxylase and testosterone 15 alpha-hydroxylations but failed to block these activities in the rat liver [12].

Enzymatic interactions of Cyp2a5


Co-localisations of Cyp2a5

  • A P450 protein co-migrating with Cyp2a-5 was also detected in rat lung microsomes [12].
  • The CYP2A5 mRNA and the corresponding protein co-localized at most sites and were predominantly detected in the olfactory region, with an expression in sustentacular cells, Bowman's gland, and duct cells [20].

Regulatory relationships of Cyp2a5

  • These data indicate that the Cyp2a-4/5 complex is regulated in a different way in DBA/2 and C57BL/6 mice and that some association exists between the development of liver damage and COH induction [18].
  • An additional AHR-dependent mechanism also regulates the proximal promoter of the Cyp2a5 gene [9].
  • The cytochrome P4502a5 (Cyp2a5) gene is expressed principally in liver and olfactory mucosa [21].

Other interactions of Cyp2a5


Analytical, diagnostic and therapeutic context of Cyp2a5


  1. Overexpression of a cytochrome P-450 of the 2a family (Cyp2a-5) in chemically induced hepatomas from female mice. Jounaïdi, Y., Bonfils, C., Périn, F., Negishi, M., Lange, R. Eur. J. Biochem. (1994) [Pubmed]
  2. Targeted disruption of the olfactory mucosa-specific Cyp2g1 gene: impact on acetaminophen toxicity in the lateral nasal gland, and tissue-selective effects on Cyp2a5 expression. Zhuo, X., Gu, J., Behr, M.J., Swiatek, P.J., Cui, H., Zhang, Q.Y., Xie, Y., Collins, D.N., Ding, X. J. Pharmacol. Exp. Ther. (2004) [Pubmed]
  3. Circadian expression of the steroid 15 alpha-hydroxylase (Cyp2a4) and coumarin 7-hydroxylase (Cyp2a5) genes in mouse liver is regulated by the PAR leucine zipper transcription factor DBP. Lavery, D.J., Lopez-Molina, L., Margueron, R., Fleury-Olela, F., Conquet, F., Schibler, U., Bonfils, C. Mol. Cell. Biol. (1999) [Pubmed]
  4. Inherent versatility of P-450 oxygenase. Conferring dehydroepiandrosterone hydroxylase activity to P-450 2a-4 by a single amino acid mutation at position 117. Iwasaki, M., Darden, T.A., Parker, C.E., Tomer, K.B., Pedersen, L.G., Negishi, M. J. Biol. Chem. (1994) [Pubmed]
  5. Chromosomal assignments of genes coding for components of the mixed-function oxidase system in mice. Genetic localization of the cytochrome P-450PCN and P-450PB gene families and the nadph-cytochrome P-450 oxidoreductase and epoxide hydratase genes. Simmons, D.L., Lalley, P.A., Kasper, C.B. J. Biol. Chem. (1985) [Pubmed]
  6. Genetic polymorphisms for a phenobarbital-inducible cytochrome P-450 map to the Coh locus in mice. Simmons, D.L., Kasper, C.B. J. Biol. Chem. (1983) [Pubmed]
  7. High expression of cytochrome P450 2a-5 (coumarin 7-hydroxylase) in mouse hepatomas. Kobliakov, V., Kulikova, L., Samoilov, D., Lang, M.A. Mol. Carcinog. (1993) [Pubmed]
  8. Close linkage of the cytochrome P450IIA gene subfamily (Cyp2a) to Cyp2b and Coh on mouse chromosome 7. Miles, J.S., Moss, J.E., Meehan, R.R., Wolf, C.R. Genomics (1990) [Pubmed]
  9. Regulation of the Cyp2a5 gene involves an aryl hydrocarbon receptor-dependent pathway. Arpiainen, S., Raffalli-Mathieu, F., Lang, M.A., Pelkonen, O., Hakkola, J. Mol. Pharmacol. (2005) [Pubmed]
  10. Evidence for induced microsomal bilirubin degradation by cytochrome P450 2A5. Abu-Bakar, A., Moore, M.R., Lang, M.A. Biochem. Pharmacol. (2005) [Pubmed]
  11. Acute sodium arsenite treatment induces Cyp2a5 but not Cyp1a1 in the C57Bl/6 mouse in a tissue (kidney) selective manner. Seubert, J.M., Webb, C.D., Bend, J.R. J. Biochem. Mol. Toxicol. (2002) [Pubmed]
  12. Cytochrome P4502A-mediated coumarin 7-hydroxylation and testosterone hydroxylation in mouse and rat lung. Honkakoski, P., Mäenpää, J., Leikola, J., Pasanen, M., Juvonen, R., Lang, M.A., Pelkonen, O., Raunio, H. Pharmacol. Toxicol. (1993) [Pubmed]
  13. Effects of lipopolysaccharide-stimulated inflammation and pyrazole-mediated hepatocellular injury on mouse hepatic Cyp2a5 expression. Gilmore, W.J., Hartmann, G., Piquette-Miller, M., Marriott, J., Kirby, G.M. Toxicology (2003) [Pubmed]
  14. Mouse steroid 15 alpha-hydroxylase gene family: identification of type II P-450(15)alpha as coumarin 7-hydroxylase. Negishi, M., Lindberg, R., Burkhart, B., Ichikawa, T., Honkakoski, P., Lang, M. Biochemistry (1989) [Pubmed]
  15. Comparative studies on coumarin and testosterone metabolism in mouse and human livers. Differential inhibitions by the anti-P450Coh antibody and metyrapone. Mäenpää, J., Syngelmä, T., Honkakoski, P., Lang, M.A., Pelkonen, O. Biochem. Pharmacol. (1991) [Pubmed]
  16. Retroviral mediated expression of human cytochrome P450 2A6 in C3H/10T1/2 cells confers transformability by 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). Tiano, H.F., Hosokawa, M., Chulada, P.C., Smith, P.B., Wang, R.L., Gonzalez, F.J., Crespi, C.L., Langenbach, R. Carcinogenesis (1993) [Pubmed]
  17. Effect of pyrazole, cobalt and phenobarbital on mouse liver cytochrome P-450 2a-4/5 (Cyp2a-4/5) expression. Hahnemann, B., Salonpää, P., Pasanen, M., Mäenpää, J., Honkakoski, P., Juvonen, R., Lang, M.A., Pelkonen, O., Raunio, H. Biochem. J. (1992) [Pubmed]
  18. Cerium-induced strain-dependent increase in Cyp2a-4/5 (cytochrome P4502a-4/5) expression in the liver and kidneys of inbred mice. Salonpää, P., Iscan, M., Pasanen, M., Arvela, P., Pelkonen, O., Raunio, H. Biochem. Pharmacol. (1992) [Pubmed]
  19. Subacute cocaine treatment changes expression of mouse liver cytochrome P450 isoforms. Powers, J.F., Shuster, L. Pharmacology (1999) [Pubmed]
  20. Cell-specific expression of CYP2A5 in the mouse respiratory tract: effects of olfactory toxicants. Piras, E., Franzén, A., Fernández, E.L., Bergström, U., Raffalli-Mathieu, F., Lang, M., Brittebo, E.B. J. Histochem. Cytochem. (2003) [Pubmed]
  21. Regulation of Cyp2a5 transcription in mouse primary hepatocytes: roles of hepatocyte nuclear factor 4 and nuclear factor I. Ulvila, J., Arpiainen, S., Pelkonen, O., Aida, K., Sueyoshi, T., Negishi, M., Hakkola, J. Biochem. J. (2004) [Pubmed]
  22. Cytochrome P450 isoforms in human fetal tissues related to phenobarbital-inducible forms in the mouse. Mäenpää, J., Rane, A., Raunio, H., Honkakoski, P., Pelkonen, O. Biochem. Pharmacol. (1993) [Pubmed]
  23. Heterogeneous nuclear ribonucleoprotein A1 and regulation of the xenobiotic-inducible gene Cyp2a5. Raffalli-Mathieu, F., Glisovic, T., Ben-David, Y., Lang, M.A. Mol. Pharmacol. (2002) [Pubmed]
  24. Liver injury and expression of cytochromes P450: evidence that regulation of CYP2A5 is different from that of other major xenobiotic metabolizing CYP enzymes. Camus-Randon, A.M., Raffalli, F., Béréziat, J.C., McGregor, D., Konstandi, M., Lang, M.A. Toxicol. Appl. Pharmacol. (1996) [Pubmed]
  25. Identification of CYP2A3 as a major cytochrome P450 enzyme in the female peripubertal rat breast. Hellmold, H., Magnusson, M., Pelto-Huikko, M., Rylander, T., Gustafsson, J., Warner, M. Mol. Pharmacol. (1998) [Pubmed]
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