Multiplicity of cytochrome P-450 and its gene structure

  • Y. Fujii-Kuriyama
  • K. Sogawa
  • Y. Suwa
  • K. Kawajiri
  • O. Gotoh


Cytochrome P-450 is widely distributed in nature from microorganisms to higher animals and plays an important role in the oxidative metabolism of a great variety of endogenous as well as exogenous lipophilic compounds (Sato & Omura, 1978; Lu & West, 1980). Recent studies involving immunological chemistry and protein chemistry have shown that multiple forms of cytochrome P-450 are present in rat liver microsomes and that their synthesis could be induced in different ways by the administration of various kinds of drugs (Sato & Omura, 1978; Lu & West, 1980). However, the molecular multiplicity and drug induction mechanism of cytochrome P-450 could best be understood by investigation at the gene (DNA) level using recombinant DNA technology.


Code Nucleotide Sequence Haem Binding Site Teine Residue Inducible Cytochrome 
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  1. BARKER, W.C. & DAYHOFF, M.O. (1972). Atlas of Protein Sequence and Structure, Vol. 5. Dayhoff, M.O., (ed.) pp. 101–110, Silver Spring: National Biomedical Research Foundation.Google Scholar
  2. FYRBERG, E.A.M., BOND, B.J., HERSHEY, N.D., MIXTER, K.S. & DAVIDSON, N. (1981). The actin genes of Drosophila: Protein coding regions are highly conserved but intron position are not. Cell, 24, 107–116.PubMedCrossRefGoogle Scholar
  3. GILBERT, W. (1978). Why genes in pieces? Nature, 271, 501.PubMedCrossRefGoogle Scholar
  4. GOTOH, O., TAGASHIRA, Y., IIZUKA, T. & FUJII-KURIYAMA, Y. (1983). Structural characteristics of cytochrome P-450. Possible location of the hemebinding cysteine in determined amino-acid sequences. J. Biochem., 93, 807–817.PubMedCrossRefGoogle Scholar
  5. HANIU, M., ARMES, L.G., TANAKA, M., YASUNOBU, K.T., SHASTRY, R.S., WAGNER, G.C. & GUNSALUS, I.C. (1982a). The primary structure of the monoxygenase P-450cam. Biophys. Res. Commun., 105, 889–894.CrossRefGoogle Scholar
  6. HANIU, M., YASUNOBU, K.T. & GUNSALUS, I.C. (1982b). Modification of the cysteine residues of cytochrome P-450cam with 2-Bromoacetamido-4-nitrophenal. Biochem. biophys. Res. Commun., 107, 1075–1081.Google Scholar
  7. JEFFREYS. (1981). Recent studies of gene evolution using recombinant DNA. In Genetic Engineering Vol. 2. Williamson, R. (ed.) pp. 1–48, London & New York: Academic Press.Google Scholar
  8. KARN, J., BRENNER, E. & BARNETT, L. (1983). Protein structural domains in the Caenorhabditis elegans unc-54 myosin heavy chain gene are not separated by introns. Proc. natn. Acad. Sci. U.S.A., 80, 4253–4257.Google Scholar
  9. KAWAJIRI, K., GOTOH, O., SOGAWA, K., TAGASHIRA, Y., MURAMATSU, M. & FUJII-KURIYAMA, Y. (1984). Coding nucleotide sequence of 3-methylcholanthrene-inducible cytochrome P-450d cDNA from rat liver. Proc. natn. Acad. Sci. U.S.A., 81, 1649–1653.Google Scholar
  10. LEICHT, M., LONG, G.G., CHANDRA, T., KURACHI, K., KIDD, V.J., NACE, M., DAVIE, E.W. & WOO, E.L.C. (1982). Sequence homology and structural comparison between the chromosomal human α1-antitrypsin and chicken ovalbumin genes. Nature, 297, 655–659.Google Scholar
  11. LOMEDICO, P., RESSENTHAL, N., EFSTRATIADIS, A., GILBERT, W., KOLODNER, R. & TIZARD, R. (1979). The structure and evolution of the two nonallelic rat preproinsulin genes. Cell, 18, 545–558.Google Scholar
  12. LU, A.Y.H. & WEST, S.B. (1980). Multiplicity of mammalian microsomal cytochromes P-450. Pharmac. Rev., 31, 277–295.Google Scholar
  13. MAXAM, A.M. & GILBERT, W. (1977). A new method for sequencing DNA. Proc. natn. Acad. Sci. U.S.A., 74, 560–564.Google Scholar
  14. MIZUKAMI, Y., FUJII-KURIYAMA, Y. & MURAMATSU, M. (1983a). Multiplicity of deoxyribonucleic acid sequences with homology to a cloned complementary deoxyribonucleic acid coding for rat phenobarbital inducible cytochrome P-450. Biochemistry, 22, 1223–1229.Google Scholar
  15. MIZUKAMI, Y., SOGAWA, K., SUWA, Y., MURAMATSU, M. & FUJII-KURIYAMA, Y. (1983b). Gene structure of a phenobarbital-inducible cytochrome P-450 in rat liver. Proc. natn. Acad. Sci. U.S.A., 80, 3958–3962.Google Scholar
  16. MOROHASHI, K., FUJII-KURIYAMA, Y., OKADA, Y., SOGAWA, K., HIROSE, T., INAYAMA, S. & OMURA, T. (1984). Molecular cloning and nucleotide sequence of cDNA for mRNA of mitochondrial cytochrome P-450(scc) of bovine adrenal cortex. Proc. natn. Acad. Sci. U.S.A. (in press).Google Scholar
  17. NEEDLEMAN, S.B. & WUNSCH, C.E. (1970). A general method applicable to search for similarities in the amino acid sequence of two proteins. J. mol. Biol., 48, 443–453.Google Scholar
  18. NISHIOKA, Y., LEDER, A. & LEDER, P. (1980). Unusual a- globin-like gene that has cleanly lost both globin intervening sequences. Proc. natn. Acad. Sci. U.S.A., 77, 2806–2809.Google Scholar
  19. SAKANO, H., ROGERS, J.H., HUPPI, K., BRACK, C., TRAUNECHER, A., MAKI, R., WELL, R. & TONEGAWA, E. (1979). Domains and the hinge region of an immunoglobulin heavy chain are encoded in separate DNA sequences. Nature, 277, 627–633.Google Scholar
  20. SATO, R. & OMURA, T., (eds) (1978). Cytochrome P-450. Tokyo/New York & London: Kodansha/Academic Press, Inc.Google Scholar
  21. SOGAWA, K., GOTOH, O., KAWAJIRI, K. & FUJIIKURIYAMA, Y. (1984). Distinct organization of methylcholanthrene-and phenobarbital-inducible cytochrome P-450 genes in the rat. Proc. natn. Acad. Sci. U.S.A., (in press).Google Scholar
  22. STEIN, J.P., CATTERALL, J.F., KRISTO, P., MEANS, A.R. & O’MALLEY, B.W. (1980). Ovomucoid intervening sequences specify functional domains and generate protein polymorphism. Cell, 21, 681–687.PubMedCrossRefGoogle Scholar
  23. TARR, G.E., BLACK, S.D., FUJITA, V.S. & COON, M.J. (1983). Complete amino acid sequence and predicted membrane topology of phenobarbital-induced cytochrome P-450 (isozyme 2) from rabbit liver microsomes. Proc. natn. Acad. Sci. U.S.A., 80, 6552–6556.CrossRefGoogle Scholar
  24. WAHLI, W., DAVID, K.B., WYLER, T., WEVER, R. & RYFFEL, G.U. (1980). Comparative analysis of the structural organization of two closely related vitellogenin genes in X. leavis. Cell, 20, 107–117.PubMedCrossRefGoogle Scholar
  25. WHITE, R.E. & COON, M.J. (1980). Oxygen activation by cytochrome P-450. A. Rev. Biochem., 49, 315–356.CrossRefGoogle Scholar

Copyright information

© Macmillan Publishers Limited 1984

Authors and Affiliations

  • Y. Fujii-Kuriyama
    • 1
  • K. Sogawa
    • 1
  • Y. Suwa
    • 1
  • K. Kawajiri
    • 2
  • O. Gotoh
    • 2
  1. 1.Department of Biochemistry, Cancer InstituteJapanese Foundation for Cancer ResearchTokyoJapan
  2. 2.Department of BiochemistrySaitama Cancer Center Research InstituteSaitamaJapan

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