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Gene Review

Por  -  P450 (cytochrome) oxidoreductase

Mus musculus

Synonyms: 4933424M13Rik, CPR, CYPOR, NADH cytochrome P450 oxydoreductase, NADPH--cytochrome P450 reductase, ...
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Disease relevance of Por

  • Hepatic gene expression changes in mouse models with liver-specific deletion or global suppression of the NADPH-cytochrome P450 reductase gene. Mechanistic implications for the regulation of microsomal cytochrome P450 and the fatty liver phenotype [1].
  • In liver-Cpr-null (with liver-specific Cpr deletion) and Cpr-low (with reduced CPR expression in all organs examined) mouse models, a reduced serum cholesterol level and an induction of hepatic P450s were observed, whereas hepatomegaly and fatty liver were only observed in the liver-Cpr-null model [1].
  • To evaluate the importance of hepatic P450s in normal homeostasis, drug pharmacology, and chemical toxicity, we have conditionally deleted the essential electron transfer protein, NADH:ferrihemoprotein reductase (EC, cytochrome P450 reductase, CPR) in the liver, resulting in essentially complete ablation of hepatic microsomal P450 activity [2].
  • The adenovirus used incorporates the hypoxia-responsive element (HRE) from the lactate dehydrogenase gene in a minimal SV40 promoter context upstream of the cDNA for P450R [3].
  • Recombinant CYP2J9 was co-expressed with NADPH-cytochrome P450 oxidoreductase (CYPOR) in Sf9 cells using a baculovirus system [4].

High impact information on Por


Chemical compound and disease context of Por

  • We assembled intact por genes from the gonococcal strains, FA19 (serogroup PIA) and FA6434 (a hybrid Por containing epitopes from serogroups PIA and PIB), and observed stable expression in E. coli without evident toxicity [9].
  • The aim of this study was to determine whether extrahepatic acetaminophen toxicity is altered in a mouse model that has liver-specific deletion of the NADPH-cytochrome P450 reductase (Cpr) gene [10].

Biological context of Por


Anatomical context of Por

  • Ninety percent of CYPOR -/- embryos isolated at days 10.5 or 11.5 of gestation could be classified as either Type I, characterized by grossly normal somite formation but having neural tube, cardiac, eye, and limb abnormalities, or Type II, characterized by a generalized retardation of development after approximately day 8.5 of gestation [12].
  • The floxed Cpr allele was subsequently deleted efficiently by crossing Cpr(lox) mice with transgenic mice having liver-specific Cre expression (Alb-Cre); the result was a decrease in the level of CPR protein in liver microsomes [13].
  • Two novel sites of expression of NADPH cytochrome P450 reductase during murine embryogenesis: limb mesenchyme and developing olfactory neuroepithelia [14].
  • Microsomal membranes from infected livers contained reduced amounts of cytochromes P450 and b5 and NADPH-cytochrome P450 reductase [15].
  • We established ES cell lines carrying a single copy of the wild-type lox Por LE mutant lox site as a target and examined the frequency of site-specific integration of a targeting vector carrying a loxP or RE mutant lox site induced by Cre transient expression [16].

Associations of Por with chemical compounds

  • A Mouse Model with Liver-Specific Deletion and Global Suppression of the NADPH-Cytochrome P450 Reductase Gene: Characterization and Utility for in Vivo Studies of Cyclophosphamide Disposition [17].
  • Hepatic CPR-null mice developed normally and were able to breed, indicating that hepatic microsomal P450-mediated steroid hormone metabolism is not essential for fertility, demonstrating that a major evolutionary role for hepatic P450s is to protect mammals from their environment [2].
  • Hepatic CPR-null mice could no longer break down cholesterol because of their inability to produce bile acids, and whereas hepatic lipid levels were significantly increased, circulating levels of cholesterol and triglycerides were severely reduced [2].
  • NOS also contains the coenzymes FAD and FMN and demonstrates significant amino acid sequence homology to NADPH-cytochrome P-450 reductase [18].
  • In wild-type male mice, P450R protein was decreased in liver after WY and DEHP treatment and in kidneys after WY treatment [19].

Regulatory relationships of Por


Other interactions of Por


Analytical, diagnostic and therapeutic context of Por

  • Western blot analysis showed that both purified proteins cross-reacted with two different monoclonal antibodies raised against P. hybrida NADPH-cytochrome c reductase and rabbit anti-Jerusalem artichoke NADPH-cytochrome P450 reductase antibodies [26].
  • Xenografts established from the clonal lines exhibited significant tumor control following MMC treatment (treated/control [T/C] 17% and 51% for DTD and P450R xenografts, respectively) that was not seen in wild-type tumors (T/C 102%) [23].
  • Immunocytochemistry of isolated mouse cells showed that the majority were positive with antibodies against three major components of the pulmonary cytochrome P-450 monooxygenase system, cytochrome P-450 isozymes 2 (IIB), 5 (IVB), and NADPH cytochrome P-450 reductase, purified from rabbit lung [27].
  • NADPH-cytochrome P450 reductase was expressed in morphologically normal lung tissue of all mice under control conditions and after treatment with beta-naphthoflavone, and was localized mainly in Clara and alveolar type II cells [28].
  • After purification of the enzyme from induced mycelia three forms of fungal CPR were detected on SDS-PAGE: a predominant form with an apparent molecular mass of 78kDa and two truncated forms [29].


  1. Hepatic gene expression changes in mouse models with liver-specific deletion or global suppression of the NADPH-cytochrome P450 reductase gene. Mechanistic implications for the regulation of microsomal cytochrome P450 and the fatty liver phenotype. Weng, Y., DiRusso, C.C., Reilly, A.A., Black, P.N., Ding, X. J. Biol. Chem. (2005) [Pubmed]
  2. Inactivation of the hepatic cytochrome P450 system by conditional deletion of hepatic cytochrome P450 reductase. Henderson, C.J., Otto, D.M., Carrie, D., Magnuson, M.A., McLaren, A.W., Rosewell, I., Wolf, C.R. J. Biol. Chem. (2003) [Pubmed]
  3. Hypoxia targeted gene therapy to increase the efficacy of tirapazamine as an adjuvant to radiotherapy: reversing tumor radioresistance and effecting cure. Cowen, R.L., Williams, K.J., Chinje, E.C., Jaffar, M., Sheppard, F.C., Telfer, B.A., Wind, N.S., Stratford, I.J. Cancer Res. (2004) [Pubmed]
  4. Cytochrome P450 CYP2J9, a new mouse arachidonic acid omega-1 hydroxylase predominantly expressed in brain. Qu, W., Bradbury, J.A., Tsao, C.C., Maronpot, R., Harry, G.J., Parker, C.E., Davis, L.S., Breyer, M.D., Waalkes, M.P., Falck, J.R., Chen, J., Rosenberg, R.L., Zeldin, D.C. J. Biol. Chem. (2001) [Pubmed]
  5. Presence of NADPH-cytochrome P450 reductase in central catecholaminergic neurones. Haglund, L., Köhler, C., Haaparanta, T., Goldstein, M., Gustafsson, J.A. Nature (1984) [Pubmed]
  6. N-acetyl-p-benzoquinone imine: a cytochrome P-450-mediated oxidation product of acetaminophen. Dahlin, D.C., Miwa, G.T., Lu, A.Y., Nelson, S.D. Proc. Natl. Acad. Sci. U.S.A. (1984) [Pubmed]
  7. Purification and characterization of cytochrome P-450 induced by benz(a)anthracene in mouse skin microsomes. Ichikawa, T., Hayashi, S., Noshiro, M., Takada, K., Okuda, K. Cancer Res. (1989) [Pubmed]
  8. Benzo(a)pyrene metabolism by murine spleen microsomes. Kawabata, T.T., White, K.L. Cancer Res. (1989) [Pubmed]
  9. Cloning and constitutive expression of structural genes encoding gonococcal porin protein in Escherichia coli and attenuated Salmonella typhimurium vaccine strains. Elkins, C., Carbonetti, N.H., Coímbre, A.J., Thomas, C.E., Sparling, P.F. Gene (1994) [Pubmed]
  10. In vivo mechanisms of tissue-selective drug toxicity: effects of liver-specific knockout of the NADPH-cytochrome P450 reductase gene on acetaminophen toxicity in kidney, lung, and nasal mucosa. Gu, J., Cui, H., Behr, M., Zhang, L., Zhang, Q.Y., Yang, W., Hinson, J.A., Ding, X. Mol. Pharmacol. (2005) [Pubmed]
  11. P450 (cytochrome) oxidoreductase (Por) maps to mouse chromosome 5, not chromosome 6. Spearow, J.L. Mamm. Genome (1995) [Pubmed]
  12. Association of multiple developmental defects and embryonic lethality with loss of microsomal NADPH-cytochrome P450 oxidoreductase. Shen, A.L., O'Leary, K.A., Kasper, C.B. J. Biol. Chem. (2002) [Pubmed]
  13. Conditional knockout of the mouse NADPH-cytochrome p450 reductase gene. Wu, L., Gu, J., Weng, Y., Kluetzman, K., Swiatek, P., Behr, M., Zhang, Q.Y., Zhuo, X., Xie, Q., Ding, X. Genesis (2003) [Pubmed]
  14. Two novel sites of expression of NADPH cytochrome P450 reductase during murine embryogenesis: limb mesenchyme and developing olfactory neuroepithelia. Keeney, D.S., Waterman, M.R. Dev. Dyn. (1999) [Pubmed]
  15. Changes in hepatic xenobiotic-metabolising enzymes in mouse liver following infection with Leishmania donovani. Coombs, G.H., Wolf, C.R., Morrison, V.M., Craft, J.A. Mol. Biochem. Parasitol. (1990) [Pubmed]
  16. Targeted integration of DNA using mutant lox sites in embryonic stem cells. Araki, K., Araki, M., Yamamura, K. Nucleic Acids Res. (1997) [Pubmed]
  17. A Mouse Model with Liver-Specific Deletion and Global Suppression of the NADPH-Cytochrome P450 Reductase Gene: Characterization and Utility for in Vivo Studies of Cyclophosphamide Disposition. Gu, J., Chen, C.S., Wei, Y., Fang, C., Xie, F., Kannan, K., Yang, W., Waxman, D.J., Ding, X. J. Pharmacol. Exp. Ther. (2007) [Pubmed]
  18. Nitric oxide synthase is a cytochrome P-450 type hemoprotein. White, K.A., Marletta, M.A. Biochemistry (1992) [Pubmed]
  19. Opposing mechanisms of NADPH-cytochrome P450 oxidoreductase regulation by peroxisome proliferators. Fan, L.Q., Coley, J., Miller, R.T., Cattley, R.C., Corton, J.C. Biochem. Pharmacol. (2003) [Pubmed]
  20. Mouse cytochrome P450 (Cyp3a11): predominant expression in liver and capacity to activate aflatoxin B1. Yanagimoto, T., Itoh, S., Sawada, M., Kamataki, T. Arch. Biochem. Biophys. (1997) [Pubmed]
  21. Molecular cloning and functional expression of a mouse cytochrome P-450 (Cyp3a-13): examination of Cyp3a-13 enzyme to activate aflatoxin B1 (AFB1). Yanagimoto, T., Itoh, S., Sawada, M., Hashimoto, H., Kamataki, T. Biochim. Biophys. Acta (1994) [Pubmed]
  22. NADPH-cytochrome P-450 reductase, cytochrome P-450 2C11 and P-450 1A1, and the aryl hydrocarbon receptor in livers of rats fed methyl-folate-deficient diets. Zhang, J., Henning, S.M., Heber, D., Choi, J., Wang, Y., Swendseid, M.E., Go, V.L. Nutrition and cancer. (1997) [Pubmed]
  23. Viral delivery of P450 reductase recapitulates the ability of constitutive overexpression of reductase enzymes to potentiate the activity of mitomycin C in human breast cancer xenografts. Cowen, R.L., Patterson, A.V., Telfer, B.A., Airley, R.E., Hobbs, S., Phillips, R.M., Jaffar, M., Stratford, I.J., Williams, K.J. Mol. Cancer Ther. (2003) [Pubmed]
  24. Hepatic mitochondrial coumarin 7-hydroxylase: comparison with the microsomal enzyme. Honkakoski, P., Kojo, A., Raunio, H., Pasanen, M., Juvonen, R., Lang, M.A. Arch. Biochem. Biophys. (1988) [Pubmed]
  25. Selenium and drug metabolism--II. Independence of glutathione peroxidase and reversibility of hepatic enzyme modulations in deficient mice. Reiter, R., Wendel, A. Biochem. Pharmacol. (1984) [Pubmed]
  26. Purification and partial characterization of NADPH-cytochrome c reductase from Petunia hybrida flowers. Menting, J.G., Cornish, E., Scopes, R.K. Plant Physiol. (1994) [Pubmed]
  27. Characterization of the cytochrome P-450 monooxygenase system in nonciliated bronchiolar epithelial (Clara) cells isolated from mouse lung. Chichester, C.H., Philpot, R.M., Weir, A.J., Buckpitt, A.R., Plopper, C.G. Am. J. Respir. Cell Mol. Biol. (1991) [Pubmed]
  28. Alterations in expression of CYP1A1 and NADPH-cytochrome P450 reductase during lung tumor development in SWR/J mice. Forkert, P.G., Lord, J.A., Parkinson, A. Carcinogenesis (1996) [Pubmed]
  29. Catalytic and immunochemical properties of NADPH-cytochrome P450 reductase from fungus Rhizopus nigricans. Makovec, T., Breskvar, K. J. Steroid Biochem. Mol. Biol. (2002) [Pubmed]
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