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Primary Structures and Regulation of Cytochrome P-450 Isozymes 2 (IIB) And 5 (IVB) and the Flavin-Containing Monooxygenase in Rabbit Liver and Lung

  • Richard M. Philpot
  • Rodolfo Gasser
  • Michael P. Lawton
Part of the NATO ASI Series Advanced Science Institutes Series book series (NSSA, volume 202)

Abstract

Cytochrome P-450 (P-450) isozymes 2 and 5, which belong to P-450 gene subfamilies IIB and IVB according to the nomenclature devised by Nebert et al. (1), comprise over 90% of the P-450 in rabbit lung and are the major drug-metabolizing enzymes in that tissue. Results of immunochemical, catalytic, and biochemical studies (2-5) suggest that orthologs of isozymes 2 and 5 also account for the majority of the pulmonary P-450 in other species (rats, mice, guinea pigs, hamsters, and monkeys). A third drug-metabolizing enzyme present in rabbit lung at a relatively high concentration is the flavin-containing monooxygenase (FMO). This enzyme, which catalyzes the oxidation of sulfur, phosphorous, and nitrogen in a wide variety of compounds (6, 7), has also been detected in lungs from a number of species (8).

Keywords

Rabbit Liver Rabbit Lung Derive Amino Acid Sequence Untreated Rabbit Liver Lung Kidney 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. 1.
    D. W. Nebert, D. R. Nelson, M. Adesnik, M. J. Coon, R. W. Estabrook, F. J. Gonzalez, F. P. Guengerich, I. C. Gunsalus, E. F. Johnson, B. Kemper, W. Levin, I. R. Phillips, R. Sato, and M. R. Waterman, The P450 superfamily: Updated listing of all genes and recommended nomenclature for the chromosomal loci, DNA 8:1 (1989).PubMedCrossRefGoogle Scholar
  2. 2.
    R. R. Vanderslice, B. A. Domin, G. Carver, and R. M. Philpot, Species-dependent expression and induction of homologues of rabbit cytochrome P-450 isozyme 5 in liver and lung, Mol. Pharmacol. 31:320 (1987).PubMedGoogle Scholar
  3. 3.
    B. A. Domin, C. J. Serabjit-Singh, R. R. Vanderslice, T. R. Devereux, J. R. Fouts, J. R. Bend, and R. M. Philpot, Tissue and cellular differences in the expression of cytochrome P-450 isozymes, in: “Proceedings of IUPHAR 9th International Congress of Pharmacology,” W. Paton, J. Mitchell, and P. Turner, eds., Macmillan Press Ltd., London (1984).Google Scholar
  4. 4.
    R. M. Philpot, B. A. Domin, T. R. Devereux, C. Harris, M. W. Anderson, J. R. Fouts, and J. R. Bend, Cytochrome P-450 monooxygenase systems of the lung: Relationships to pulmonary toxicity, in: “Microsomes and Drug Oxidations, Proceedings of the 6th Interna tional Symposium,” A. R. Bobbis, J. Caldwell, F. DeMateis, and C. R. Elcombe, eds., Taylor and Francis Ltd., London (1985).Google Scholar
  5. 5.
    R. Gasser and R. M. Philpot, Structure and function of homologous pulmonary and hepatic isozymes of cytochrome P-450, in: “Microsomes and Drug Oxidations, Proceedings of the 7th International Symposium,” J. Minors, D. J. Birkett, R. Drew, and M. McManus, eds., Taylor and Francis Ltd., London (1988).Google Scholar
  6. 6.
    D. M. Ziegler, Flavin-containing monooxygenases: Catalytic mechaanisms and substrate specificities, Drug Metab. Rev. 6:1 (1988).CrossRefGoogle Scholar
  7. 7.
    B. P. Smyser and E. Hodgson, Metabolism of phosphorous-containing compounds by pig liver microsomal FAD-containing monooxygenase, Biochem. Pharmacol. 34:1145 (1985).PubMedCrossRefGoogle Scholar
  8. 8.
    R. E. Tynes and R. M. Philpot, Tissue-and species-dependent expres sion of multiple forms of mammalian microsomal flavin-containing monooxygenase, Mol. Pharmacol. 31:569 (1987).PubMedGoogle Scholar
  9. 9.
    C. J. Serabjit-Singh, C. R. Wolf, and R. M. Philpot, The rabbit pulmonary monooxygenase system: Immunochemical and biochemical characterization of the enzyme components, J. Biol. Chem. 254:9901 (1979).PubMedGoogle Scholar
  10. 10.
    S. R. Slaughter, C. R. Wolf, J. P. Marciniszyn, and R. M. Philpot, The rabbit pulmonary monooxygenase system: Partial structural characterization of the cytochrome P-450 components and comparison to the hepatic cytochrome P-450, J. Biol. Chem. 256:2499 (1981).PubMedGoogle Scholar
  11. 11.
    Z. Parandoosh, V. S. Fujita, M. J. Coon, and R. M. Philpot, Cytochrome P-450 isozymes 2 and 5 in rabbit lung and liver: Comparisons of structure and inducibility, Drug Metab. Dispo. 15:59 (1987).Google Scholar
  12. 12.
    I. G. C. Robertson, C. J. Serabjit-Singh, J. E. Croft, and R. M. Philpot, The relationship between increases in the hepatic content of cytochrome P-450, form 5, and in the metabolism of aromatic amines to mutagenic products following treatment of rabbits with phenobarbital, Mol. Pharmacol. 24:156 (1983).PubMedGoogle Scholar
  13. 13.
    E. Williams, D. M. Ziegler, D. J. Nordin, S. E. Hale, and B. S. S. Masters, Rabbit lung flavin-containing monooxygenase is immuno-chemically and catalytically distinct from the liver enzyme, Biochem. Biophys. Res. Commun. 125:116 (1984).PubMedCrossRefGoogle Scholar
  14. 14.
    R. E. Tynes, P. J. Sabourin, and E. Hodgson, Identification of distinct hepatic and pulmonary forms of microsomal flavin-containing monooxygenase in the mouse and rabbit, Biochem. Biophvs. Res. Commun. 126:1069 (1985).CrossRefGoogle Scholar
  15. 15.
    R. E. Tynes, P. J. Sabourin, E. Hodgson, and R. M. Philpot, Formation of hydrogen peroxide and N-hydroxylated amines catalyzed by pulmonary flavin-containing monooxygenases in the presence of primary alkylamines, Arch. Biochem. Biophvs. 251:654 (1986).CrossRefGoogle Scholar
  16. 16.
    R. Gasser, M. Negishi, and R. M. Philpot, Primary sequences of multiple forms of cytochrome P-450 isozyme 2 derived from rabbit pulmonary and hepatic cDNAs, Mol. Pharmacol. 32:22 (1988).Google Scholar
  17. 17.
    J. M. Chirgwin, A. E. Przybyla, R. J. Macdonald, and W. J. Rutter, Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease, Biochemistry 18:5294 (1979).PubMedCrossRefGoogle Scholar
  18. 18.
    V. Glisin, R. Crkvenjakov, and C. Byus, Ribonucleic acid isolated by cesium chloride centrifugation, Biochemistry 13:2633 (1974).PubMedCrossRefGoogle Scholar
  19. 19.
    M. Gross-Bellard, P. Oudet, and P. Chambon, Isolation of highmolecular-weight DNA from mammalian cells, Eur. J. Biochem. 36:32 (1973).PubMedCrossRefGoogle Scholar
  20. 20.
    P. J. Enrietto, L. N. Payne, and M. J. Hayman, A recovered avian myelocytomaosis virus that induces lymphomas in chickens: Pathogenic properties and their molecular basis, Cell 35:369 (1983).PubMedCrossRefGoogle Scholar
  21. 21.
    R. Gasser, R. E. Tynes, M. P. Lawton, K. K. Korsmeyer, D. M. Ziegler, and R. M. Philpot, The flavin-containing monooxygenase expressed in pig liver: Primary sequence, distribution and evidence for a single gene, Biochemistry 29:119 (1990).PubMedCrossRefGoogle Scholar
  22. 22.
    P. L. Deininger, Random subcloning of sonicated DNA: Application to shotgun DNA sequence analysis, Anal. Biochem. 129:216 (1983).PubMedCrossRefGoogle Scholar
  23. 23.
    J. Messing, New M13 vectors for cloning, Methods Enzymol. 57:20 (1983).CrossRefGoogle Scholar
  24. 24.
    F. Sanger, S. Nicklen, and A. R. Coulson, DNA sequencing with chain terminating inhibitors. Proc. Natl. Acad. Sci. USA 74:5463 (1977).PubMedCrossRefGoogle Scholar
  25. 25.
    M. D. Biggin, T. J. Gibson, and G. F. Hong, Buffer gradient gels and [35S] label as an aid to rapid DNA sequence determination, Proc. Natl. Acad. Sci. USA 80:3963 (1983).PubMedCrossRefGoogle Scholar
  26. 26.
    R. Kraft, J. Tardiff, K. S. Krauter, and L. A. Leinwand, Using mineprep plamid DNA for sequencing double stranded templates with sequenase, BioTechniques 6:544 (1988).PubMedGoogle Scholar
  27. 27.
    J. Devereux, P. Haeberli, and O. Smithies, A comprehensive set of sequence analysis programs for the VAX, Nucleic Acids Res. 12:387 (1984).PubMedCrossRefGoogle Scholar
  28. 28.
    W. J. Wilbur and D. J. Lipman, Rapid similarity searches of nucleic acid and protein data banks, Proc. Natl. Acad. Sci. USA 80:726 (1983).PubMedCrossRefGoogle Scholar
  29. 29.
    A. Feinberg and B. Vogelstein, A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity, Anal. Biochem. 132:6 (1983).PubMedCrossRefGoogle Scholar
  30. 30.
    E. M. Southern, Detection of specific DNA fragments separated by gel electrophoresis, J. Mol. Biol. 98:503 (1975).PubMedCrossRefGoogle Scholar
  31. 31.
    G. E. Tarr, S. D. Black, V. S. Fujita, and M. J. Coon, Complete amino acid sequence and predicted membrane topology of phenobarbital-induced cytochrome P-450 (isozyme 2) from rabbit liver microsomes, Proc. Natl. Acad. Sci. USA 80:1169 (1983).CrossRefGoogle Scholar
  32. 32.
    C. J. Omiecinski, Tissue-specific expression of rat mRNAs homologous to cytochrome P-450b and P-450e, Nucleic Acids Res. 14:1525 (1986).PubMedCrossRefGoogle Scholar
  33. 33.
    F. G. Walz, Jr., G. P. Vlasuk, C. J. Omiecinski, E. Bresnick, P. E. Thomas, D. E. Ryan, and W. Levin, Multiple, immunoidentical forms of phenobarbital-induced rat liver cytochrome P-450 are encoded by different mRNAs, J. Biol. Chem. 257:4023 (1982).PubMedGoogle Scholar
  34. 34.
    A. Rampersaud and F. G. Walz, Jr., At least six forms of extremely homologous cytochrome P-450 are encoded at two closely linked genetic loci, Proc. Natl. Acad. Sci. USA 80:6542 (1983).PubMedCrossRefGoogle Scholar
  35. 35.
    R. Gasser and R. M. Philpot, Primary structures of cytochrome P-450 isozyme 5 from rabbit and rat and regulation of species-dependent expression and induction in lung and liver: Identification of cytochrome P-450 gene subfamily IVB, Mol. Pharmacol. 35:617 (1989).PubMedGoogle Scholar
  36. 36.
    J. P. Hardwick, B.-J. Song, E. Huberman, and F. J. Gonzalez, Isolation, complementary DNA sequence, and regulation of rat hepatic lauric acid ω-hydroxylase (cytochrome P-450LAω): Identification of a new cytochrome P-450 gene family. J. Biol. Chem. 262:810 (1987).Google Scholar
  37. 37.
    S. Matsubara, S. Yamamoto, K. Sogawa, N. Yokotne, Y. Fujii-Kuriyama, M. Haniu, J. E. Shively, O. Gotoh, E. Kusunose, and M. Kusunuse, cDNA cloning and inducible expression during pregnancy of the mRNA for rabbit pulmonary prostaglandin ω-hydroxylase (cytochrome P-450 p-2), J. Biol. Chem. 262:13366 (1987).PubMedGoogle Scholar
  38. 38.
    M. P. Lawton, R. Gasser, R. E. Tynes, E. Hodgson, and R. M. Philpot, The flavin-containing monooxygenase enzymes expressed in rabbit liver and lung are products of related but distinctly different genes, J. Biol. Chem. 265:5855 (1990).PubMedGoogle Scholar
  39. 39.
    T. Yamada, C. J. Palm, B. Brooks, and T. Kosuge, Nucleotide sequences of the Pseudomonas savastanoi indoleacetic acid genes show homology with Agrobacterium tumefaciens T-DNA, Proc. Natl. Acad. Sci. USA 82:6522 (1985).PubMedCrossRefGoogle Scholar
  40. 40.
    N. L. Brown, S. J. Ford, R. D. Pridmore, and D. C. Fritzinger, Nucleotide sequence of a gene from the Pseudomonas transposon Tn501 encoding mercuric reductase, Biochemistry 22:4089 (1983).PubMedCrossRefGoogle Scholar
  41. 41.
    Y. Nonaka, H. Murakami, Y. Yabusaki, S. Kuramitsu, H. Kagamiyama, T. Yamano, and M. Okamoto, Molecular cloning and sequence analysis of full-length cDNA for mRNA of adrenodoxin oxidoreductase from bovine adrenal cortex, Biochem. Biophys. Res. Commun. 145:1239 (1987).PubMedCrossRefGoogle Scholar
  42. 42.
    R. L. Krauth-Siegel, R. Blatterspiel, M. Saleh, E. Schütz, R. H. Schirmer, and R. Untucht-Grau, Glutathione reductase from human erythrocytes. The sequences of the NADPH domain and of the interface domain, Eur. J. Biochem. 121:259 (1982).PubMedCrossRefGoogle Scholar
  43. 43.
    T. R. Devereux, R. M. Philpot, and J. R. Fouts, The effect of Hg2+ on rabbit hepatic and pulmonary microsomal and purified N,N-dimethylaniline N-oxidases, Chemico-Biol. Interact. 18:277 (1977).CrossRefGoogle Scholar
  44. 44.
    Y. Ohmiya and H. M. Mehendale, Species differences in the pulmonary N-oxidation of chlorpromazine and imipramine, Pharmacology 22:289 (1984).CrossRefGoogle Scholar
  45. 45.
    L. L. Poulsen and D. M. Ziegler, The liver microsomal FAD-containing monooxygenase: Spectral characterization and kinetic studies, J. Biol. Chem. 254:6449 (1979).PubMedGoogle Scholar

Copyright information

© Plenum Press, New York 1991

Authors and Affiliations

  • Richard M. Philpot
    • 1
  • Rodolfo Gasser
    • 1
  • Michael P. Lawton
    • 1
  1. 1.Laboratory of Cellular and Molecular PharmacologyNational Institute of Environmental Health SciencesUSA

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