Skip to main content
SpringerLink
Log in

The Role of Cytochrome P-450 in Microsomal Mixed Function Oxidation Reactions

  • Conference paper
Biochemie des Sauerstoffs

Abstract

The central role of oxygen in many metabolic reactions of the cell is the general theme of this colloquium. Prof. Lubbers [1] has described the role of the hemoproteins, hemoglobin and myoglobin in oxygen transfer reactions whereas Prof. Chance [2] has presented his elegant experiments on the reduction of oxygen by the mitochondrial respiratory chain. The present discussion will center on a different type of reaction in which oxygen participates in many mammalian cells. These reactions are those which have been termed [3] mixed function oxidation reactions — reactions which are catalyzed [4] by a unique hemoprotein called cytochrome P-450.

Supported in part by a U.S. Public Health Service Research Grant, GM 12202, and a grant from the National Science Foundation, AB 2451.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 54.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 69.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Lubbers, D. W.: Intercapillärer O2-Transport und intracelluläre Sauerstoffkonzentration. Mosbacher Colloquium 19, 67–92 (1968).

    Google Scholar 

  2. Chance, B., and M. Pring: Logic in the design of the respiratory chain. Mosbacher Colloquium 19, 102–126 (1968).

    Google Scholar 

  3. Mason, H. S.: Mechanisms of oxygen metabolism. Advanc. Enzymol. 19, 79–233 (1957).

    CAS  Google Scholar 

  4. Estabrook, R. W., D. Y. Cooper, and O. Rosenthal: The light reversible carbon monoxide inhibition of steroid C 21-hydroxylase systems of the adrenal cortex. Biochem. Z. 338, 741–755 (1963).

    PubMed  CAS  Google Scholar 

  5. Hayano, M., and R. I. Dorfman: Hydroxylation of steroids. Arch. Biochem. 36, 237 (1952).

    Article  PubMed  CAS  Google Scholar 

  6. Hayaishi, O., S. Rothberg, and A. H. Mehler: In: Oxygenases, Chapter I. Ed. O. Hayaishi. New York and London: Academic Press 1962.

    Google Scholar 

  7. Gillette, J. R.: Biochemistry of drug oxidation and reduction by enzymes in hepatic endoplasmic reticulum. Advanc. Pharmac. 4, 219–261 (1967).

    Google Scholar 

  8. Brodie, B. B., J. Axelrod, Y. R. Cooper, L. Gaudette, B. N. La Du, C. Mitoma, and S. Udenfriend: Detoxication of drugs and other foreign compounds by liver microsomes. Science 121, 603 (1955).

    Article  PubMed  CAS  Google Scholar 

  9. Brodie, B. B., J. Axelrod: The fate of antipyrine in man. J. Pharmacol, exp. Ther. 98, 97–112 (1950).

    CAS  Google Scholar 

  10. Conney, A. H., C. Davison, R. Gastel, and J. J. Burns: Adaptive increases in drug metabolizing enzymes induced by phenobarbital and other drugs. Advanc. Enzym Regulation 1, 189–214 (1963).

    Article  CAS  Google Scholar 

  11. Gillette, J. R.: In: Metabolism of drugs and other foreign compounds by enzymatic mechanisms. Ed. E. Jucker. Fortschr. Arzneimittelforsch. 6, 11–73 (1965).

    Google Scholar 

  12. Brodie, B. B., J. R. Gillette, and B. N. La Du: Enzymatic metabolism of drugs and other foreign compounds. Ann. Rev. Biochem. 27, 427 bis 454 (1958).

    Article  Google Scholar 

  13. Grant, J. K., and A. C. Brownie: The role of fumarate and TPN in steroid enzymic 11 β-hydroxylation. Biochim. biophys. Acta (Amst.) 18, 433–445 (1955).

    Article  CAS  Google Scholar 

  14. Strittmatter, C. F., and E. G. Ball: A hemochromogen component of liver microsomes. Proc. nat. Acad. Sci. (Wash.) 38, 19–37 (1952).

    Article  CAS  Google Scholar 

  15. Pappenheimer, A. M., and B. Chance: Cytochrome b 5 and the dihydro-Coenzyme-oxidase system in the cecropia silkworm. J. biol. Chem. 209, 915–929 (1954).

    PubMed  CAS  Google Scholar 

  16. Strittmater, Ph., and S. F. Velick: The isolation and properties of microsomal cytochrome. J. biol. Chem. 221, 253–264 (1955).

    Google Scholar 

  17. Klingenberg, M.: Pigments of rat liver microsomes. Arch. Biochem. 75, 376–386 (1958).

    Article  PubMed  CAS  Google Scholar 

  18. Omura, T., and R. Sato: The carbon monoxide-binding pigment of liver microsomes. J. biol. Chem. 237, 2370–2385 (1964).

    Google Scholar 

  19. Ryan, K. G., and L. Engel: Hydroxylation of steroids at carbon- 21. J. biol. Chem. 225, 103–114 (1957).

    PubMed  CAS  Google Scholar 

  20. Conney, A. H., R. R. Brown, G. A. Miller, and E. C. Miller: The metabolism of methylated aminoazo dyes. VI. Intracellular distribution and properties of the demethylase system. Cancer Res. 17, 628 bis 633 (1957).

    PubMed  CAS  Google Scholar 

  21. Warburg, O.: Heavy metal prosthetic groups and enzyme action, chapters XII and XIII. London and New York: Oxford Univer. Press (Clarendon) 1949.

    Google Scholar 

  22. Cooper, D. Y., S. Levin, S. Narasimhulu, O. Rosenthal, and R. W. Estabrook: Photochemical action spectrum of the terminal oxidase of mixed function oxidase system. Science 147, 400 (1965).

    Article  PubMed  CAS  Google Scholar 

  23. Warburg, O., u. F. Kubowitz: Ist die Atmungshemmung durch Kohlenoxyd vollständig? Biochem. Z. 214, 19–32 (1929).

    CAS  Google Scholar 

  24. Rosenthal, O., and D. Cooper: Methods of determining the photochemical action spectrum. In: Methods in enzymology, 10, 616–629. Eds. Estabrook, R. W., and M. E. Pullman. New York and London: Academic Press 1967.

    Google Scholar 

  25. Claude, A.: Particulate components of normal and tumor cells. Science 91, 77–89 (1940).

    Article  PubMed  CAS  Google Scholar 

  26. Chance, B.: Techniques for the assay of the respiratory enzymes. In: Methods in enzymology, vol. IV, 273–329. Eds. Colowick, S. P., and N. O. Kaplan. New York: Academic Press 1957.

    Google Scholar 

  27. Remmer, H., and H. J. Merker: Drug induced changes in the liver endoplasmic reticulum association with drug metabolizing enzyme. Ann. N.Y. Acad. Sci. 142, 1657–1658 (1963).

    CAS  Google Scholar 

  28. Orrenius, S., and L. Ernster: Phenobarbital induced synthesis of the oxidative demethylating enzymes of rat liver microsomes. Biochem. biophys. Res. Commun. 16, 60–65 (1964).

    Article  PubMed  CAS  Google Scholar 

  29. Dallner, G., Ph. Siekewitz, and G. E. Palade: Biogenesis of endoplasmic reticulum membranes. J. cell. Biol. 30, 97–120 (1966).

    Article  PubMed  CAS  Google Scholar 

  30. Omura, T., R. Sato, D. Y. Cooper, O. Rosenthal, and R. W. Estabrook: Function of cytochrome P-450 of microsomes. Fed. Proc. 24, 1181–1189 (1965).

    PubMed  CAS  Google Scholar 

  31. Kimura, T., and K. Suzuki: Components of the electron transport system in adrenal steroid hydroxylase and purification of a non-heme iron protein (Adrenodoxin). J. biol. Chem. 242, 485–491 (1967).

    PubMed  CAS  Google Scholar 

  32. Omura, T., E. Sanders, D. Y. Cooper, O. Rosenthal, and R. W. Estabrook: Isolation of a non-heme iron protein of adrenal cortex functional as a TPNH-flavorprotein-cytochrome P-450 reductase for hydroxylation reactions. In: Non-heme iron proteins: Role in energy conversion., p. 401–415. (Ed. Anthony San Pietro. Yellow Springs, Ohio: The Antioch Press 1965.

    Google Scholar 

  33. Cooper, D. Y., H. Schleyer, and O. Rosenthal: Role of cytochrome P-450 in mixed function oxidases, using the reconstituted 11 β-steroid hydroxylase of adrenal mitochondria as an example. Constance Colloquium on the Mechanism of Mixed Function Oxygenation. Constance, Germany: In press, 1968.

    Google Scholar 

  34. Simpson, E., and G. S. Boyd: Partial resolution of the mixed-function oxidase involved in the cholesterol side-chain cleavage reaction in bovine adrenal mitochondria. Biochem. biophys. Res. Commun. 28, 945–950 (1967).

    CAS  Google Scholar 

  35. Greengard, P., S. Psychoyos, H. H. Tallan, D. Y. Cooper, O. Rosenthal, and R. W. Estabrook: Aldosterone synthesis by adrenal mitochondria. III. Participation of cytochrome P-450. Arch. Biochem. 121, 298–309 (1967).

    Article  PubMed  CAS  Google Scholar 

  36. Omura, T., W. Cammer, D. Cooper, O. Rosenthal, and R. W. Estabrook: Cytochrome P-450 and the electron transport sequence associated with hydroxylation reaction. Sonderdruck aus Abhandlungen der Deutschen Akademie der Wissenschaften zu Berlin. Elektrochemische Methoden und Prinzipien in der Molekularbiologie, S. 25–32. III. Jenaer Symposium, 25. bis 29. Mai 1965. Berlin: Akademie Verlag 1966.

    Google Scholar 

  37. Beinert, H., and R. H. Sands: Studies on succinic and DPNH dehydrogenase preparations by paramagnetic resonance (EPR) spectroscopy. Biochem. biophys. Res. Commun. 3, 41–46 (1960).

    CAS  Google Scholar 

  38. Beinert, H.: Complexities in metal-flavoprotein function revealed by EPR-spectro-scopy. In: Flavins and flavoproteins, B.B.A. Library, vol. 8, p. 48–74. Ed. E. C. Slater. Amsterdam-London-New York: Elsevier Publ. Comp. 1966.

    Google Scholar 

  39. Remher, H., J. Schenkhan, R. W. Estabrook, H. Sasahe, J. Gillette, S. Narasihhulu, D. Y. Cooper, and O. Rosenthal: Drug interaction with hepatic microsomal cytochrome. Mol. Pharm. 2, 187–190 (1966).

    Google Scholar 

  40. Schenkhan, J. B., H. Rehher, and R. W. Estabrook: Spectral studies of drug interaction with hepatic microsomal cytochrome. Mol. Pharm. 3, 113–123 (1967).

    Google Scholar 

  41. Ihai, Y., and R. Sato: Substrate interaction with hydroxylase system in liver microsomes. Biochem. biophys. Res. Commun. 22, 620–626 (1966).

    Article  Google Scholar 

  42. Narasihhulu, S., D. Y. Cooper, and O. Rosenthal: Spectrophoto-metric properties of a triton clarified steroid 21-hydroxylase system of adrenocortical microsomes. Life Sci. 4, 2101–2107 (1965).

    Article  Google Scholar 

  43. Estabrook, R. W., J. B. Schenkman, W. Conner, H. Rehher, D. Y. Cooper, S. Narasimhulu, and O. Rosenthal: Cytochrome P-450 and mixed function oxidations. In: Biological and chemical aspects of oxygenases, p. 153–194. Eds. Bloch, K., and O. Hayaishi. Kyoto (Japan) 1966.

    Google Scholar 

  44. Camher, W., J. B. Schenkhan, and R. W. Estabrook: EPR-measurement of substrate interaction with cytochrome P-450. Biochem. biophys. Res. Commun. 23, 264–268 (1966).

    Article  Google Scholar 

  45. Hashihoto, Y., T. Yamaro, and H. S. Mason: An electron spin resonance study of microsomal electron transport. J. biol. Chem. 237, 3843 (1962).

    Google Scholar 

  46. Cohen, B., and R. W. Estabrook: In: Microsomes and drug oxidation. In press.

    Google Scholar 

  47. Hildebrandt, A., H. Rehher, and R. W. Estabrook: Cytochrome P-450 in liver microsomes.- One pigment or many ? Biochem. biophys. Res. Commun. 30, 607–612 (1968).

    Article  PubMed  CAS  Google Scholar 

  48. Hildebrandt, A., and R. W. Estabrook: Spectrophotometric studies of cytochrome P-450 of liver microsomes after induction with phenobarbital and 3-methylcholanthrene. Sympos. on microsomes and drug oxidase, Bethesda, Maryland 1968.

    Google Scholar 

  49. Alvares, A. P., G. Schilling, W. Levin, and R. Kuntzman: Studies on the induction of CO-binding pigment in liver microsomes by phenobarbital and 3-methylcholanthrene. Biochem. biophys. Res. Commun. 29, 521–526 (1967).

    Article  PubMed  CAS  Google Scholar 

  50. Imai, Y., and R. Sato: Evidence for two forms of P-450 hemoprotein in microsomal membranes. Biochem. biophys. Res. Commun. 23, 5–10 (1966).

    Article  PubMed  CAS  Google Scholar 

  51. Sladek, N. E., and G. Y. Mannering: Evidence for a new P-450 hemoprotein in hepatic microsomes from methylcholanthrene treated rats. Biochem. biophys. Res. Commun. 24, 688–693 (1966).

    Article  Google Scholar 

  52. Kinoshita, T., and S. Horie: Studies on P-450. III. On the absorption spectrum of P-450 in rabbit liver microsomes. J. Biochem. 61, 26 (1967).

    PubMed  CAS  Google Scholar 

  53. Gunsalus, I. C.: Mosbacher Colloquium 19, 193 (1968).

    Google Scholar 

  54. Staudinger, Hj., B. Kerekjarto, V. Ullrich, and Z. Zubrzycki: A study on the mechanism of microsomal hydroxylation. In: Oxidases and related redox systems 2, 815–837. Eds. King, T. E., H. S. Mason, and H. Morrison. Proceedings of a Symposium held in Amherst, Mass., July 15–19 (1964). New York, London, Sydney: John Wiley and Sons, Inc. 0000.

    Google Scholar 

  55. Staudinger, Hj.: In the discussion of a paper by R. Sato: State of existence and function of P-450 in microsomal hydroxylation. In: Bloch, K., and O. Hayaishi: Biological and chemical aspects of oxygenases. Symposium on Oxygenases. Kyoto (Japan), May 16–19, 1966.

    Google Scholar 

  56. Kampffmeyer, H., and M. Kiese: The hydroxylation of aniline and nethylaniline by microsomal enzymes at low oxygen pressures. Biochem. Z. 339, 454 (1964).

    PubMed  CAS  Google Scholar 

  57. Estabrook, R. W., A. Hildebrandt, and V. Ullrich: Oxygen interaction with cytochrome P-450. Constance-Colloquium on the mechanism of mixed function oxygenation. Constance, Germany 1968 (In press).

    Google Scholar 

  58. Ullrich, V., B. Cohen, D. Y. Cooper, and R. W. Estabrook: Reactions of cytochrome P-450. Symposium on Cytochromes, Osaka, Japan, August 16–18, 1967, 345–350. (In press).

    Google Scholar 

  59. Conney, A. H.: Pharmacol. Rev. 19, 317 (1967).

    PubMed  CAS  Google Scholar 

  60. Conney, A. H., and A. Klutch: J. biol. Chem. 238, 1611 (1963).

    PubMed  CAS  Google Scholar 

  61. Das, M. L., S. Orrenius, and L. Ernster: Europ. J. Biochem. 4, 519 (1968).

    Article  PubMed  CAS  Google Scholar 

  62. Lotlikar, P. D., M. Enomoto, E. C. Miller, and J. A. Miller: Cancer Res. 24, 1835 (1964).

    PubMed  CAS  Google Scholar 

  63. Orrenius, S.: In: The interaction of drugs and subcellular components in animal cells, p. 97. Ed. P. N. Campbell. London: Churchill 1968.

    Google Scholar 

  64. Orrenius, S., Y. Gnosspelius, M. L. Das, and L. Ernster: In: Structure and function of the endoplasmic reticulum in animal cells, p. 81. Ed. F. C. Gran. Oslo: Universitetsforlaget 1968.

    Google Scholar 

Download references

Author information

Author notes

  1. R. W. Estabrook, A. Hildebrandt, H. Remmer, J. B. Schenkman, O. Rosenthal & D. Y. Cooper

    Present address: Department of Biochemistry, Southwestern Medical School at Dallas of the University of Texas, Dallas, Texas, USA

Authors and Affiliations

  1. Department of Biophysics and Physical Biochemistry, Johnson Research Foundation, USA

    R. W. Estabrook, A. Hildebrandt, H. Remmer, J. B. Schenkman, O. Rosenthal & D. Y. Cooper

  2. Harrison Department of Surgical Research, School of Medicine, University of Pennsylvania, USA

    R. W. Estabrook, A. Hildebrandt, H. Remmer, J. B. Schenkman, O. Rosenthal & D. Y. Cooper

  3. Institute for Toxicology, University of Tübingen, Tübingen, Germany

    R. W. Estabrook, A. Hildebrandt, H. Remmer, J. B. Schenkman, O. Rosenthal & D. Y. Cooper

  4. Department of Biochemistry, University of Stockholm, Sweden

    Sten Orrenius

  5. Wenner Gren Institute, Univ. of Stockholm, Sweden

    L. Ernster

Authors
  1. R. W. Estabrook
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. A. Hildebrandt
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. H. Remmer
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. J. B. Schenkman
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. O. Rosenthal
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. D. Y. Cooper
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Sten Orrenius
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. L. Ernster
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Max-Planck-Institut für Ernährungsphysiologie, D-4600, Dortmund, Deutschland

    B. Hess

  2. Physiologisch-chemisches Institut, Justus-Liebig-Universität, D-6300, Gießen, Deutschland

    Hj. Staudinger

Rights and permissions

Reprints and permissions

Copyright information

© 1968 Springer-Verlag Berlin · Heidelberg

About this paper

Cite this paper

Estabrook, R.W. et al. (1968). The Role of Cytochrome P-450 in Microsomal Mixed Function Oxidation Reactions. In: Hess, B., Staudinger, H. (eds) Biochemie des Sauerstoffs. Colloquium der Gesellschaft für Biologische Chemie 24.–27. April 1968 in Mosbach/Baden, vol 19. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-85765-2_6

Download citation

  • DOI: https://doi.org/10.1007/978-3-642-85765-2_6

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-540-04067-5

  • Online ISBN: 978-3-642-85765-2

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation