Radical Intermediates in the Catalytic Cycles of Cytochrome P-450

  • Alfin D. N. Vaz
  • Elizabeth S. Roberts
  • Minor J. Coon
Part of the Basic Life Sciences book series (BLSC, volume 49)


Cytochrome P-450 is the term used for an unusual and very large family of heme proteins that have a cysteine thiolate ligated to the fifth coordination site of heme iron, and in the reduced state form unique CO complexes that have a Soret band at around 450 nm.1 This family of cytochromes consists of constitutive forms, such as the steroid-oxygenating enzymes, and inducible forms that oxygenate a large variety of naturally occurring and foreign compounds.2 Unlike most enzyme catalysts, this versatile class of heme proteins catalyzes a variety of both oxidative and reductive reactions. Oxidatively, they are capable of effecting both aliphatic and aromatic hydrocarbon hydroxylation, olefin epoxidation, dealkylation at N, O, and S atoms, N-oxidation, sulfoxidation, peroxidation, and carbon-carbon bond cleavage.1,3 Reductively, they are capable of electron transfer reactions to azo, nitro, N-oxide, epoxide, peroxy, and alkyl halide groups, thus justifying the term “cytochrome” for these catalysts. Substrates for P-450 include endobiotics like steroids, fatty acids, and prostaglandins, and xenobiotics like drugs, pesticides, and petroleum products of aliphatic or aromatic nature.


Catalytic Cycle Heme Iron Heme Protein Superoxide Radical Anion Reductive Cleavage 
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.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    R. E. White and M. J. Coon, Oxygen activation by cytochrome P-450, Annu. Rev. Biochem. 49:315–356 (1980).PubMedCrossRefGoogle Scholar
  2. 2.
    S. D. Black and M. J. Coon, Comparative structures of P-450 cytochromes, in: “Cytochrome P-450,” P. R. Ortiz de Montellano, ed., Plenum Press, New York (1986).CrossRefGoogle Scholar
  3. 3.
    C. R. Jefcoate, Cytochrome P-450 enzymes in sterol biosynthesis and metabolism, in: “Cytochrome P-450,” P.R. Ortiz de Montellano, ed., Plenum Press, New York (1986).Google Scholar
  4. 4.
    A. Y. H. Lu, K. W. Junk, and M. J. Coon, Resolution of the cytochrome P-450-containing ω-hydroxylation system of liver microsomes into three components, J. Biol. Chem. 244:3714–3721 (1969).PubMedGoogle Scholar
  5. 5.
    H. W. Strobel, A. Y. H. Lu, J. Heidema, and M. J. Coon, Phosphatidylcholine requirement in the enzymatic reduction of hemoprotein P-450 and in fatty acid, hydrocarbon, and drug hydroxylation, J. Biol. Chem. 245:4851–4854 (1970).PubMedGoogle Scholar
  6. 6.
    M. J. Coon, A. D. N. Vaz, L. D. Gorsky, and D. Pompon, Alternate pathways for dioxygen and peroxide activation and reduction, in: “Cytochrome P-450, Biochemistry, Biophysics and Induction,” L. Vereczkey and K. Magyar, eds., Elsevier, Amsterdam, and Akademiai Kiado, Budapest (1985).Google Scholar
  7. 7.
    M. Sharrock, P. G. Debrunner, C. Schulz, J.D. Lipscomb, V. Marshall, and I. C. Gunsalus, Mössbauer studies of cytochrome P-450cam, Biochemistry 12:258–265 (1973).PubMedCrossRefGoogle Scholar
  8. 8.
    L. D. Gorsky, D. R. Koop, and M. J. Coon, On the stoichiometry of the oxidase and monooxygenase reactions catalyzed by liver microsomal cytochrome P-450. Products of oxygen reduction, J. Biol. Chem. 259:6812–6817 (1984).PubMedGoogle Scholar
  9. 9.
    B. Bösterling and J. R. Trudell, Spin trap evidence for production of superoxide radical anions by purified NADPH-cytochrome P-450 reductase, Biochem. Biophys. Res. Commun. 98:569–575 (1981).PubMedCrossRefGoogle Scholar
  10. 10.
    D. D. Oprian, L. D. Gorsky, and M. J. Coon, Properties of the oxygenated form of liver microsomal cytochrome P-450, J. Biol. Chem. 258:8684–8691 (1983).PubMedGoogle Scholar
  11. 11.
    T. L. Poulos, The crystal structure of cytochrome P-450cam, in: “Cytochrome P-450,” P. R. Ortiz de Montellano, ed., Plenum Press, New York (1986).CrossRefGoogle Scholar
  12. 12.
    A. G. Krainev, L. M. Weiner, I. S. Alferyev, and N. M. Slynko, Bifunctional compound study of the active center location of cytochrome P-450 in a microsomal membrane (‘float’ molecules method), Biochem. Biophys. Acta 818:96–104 (1985).PubMedCrossRefGoogle Scholar
  13. 13.
    M. J. Coon and A. D. N. Vaz, Radical intermediates in peroxide-dependent reactions catalyzed by cytochrome P-450, J. Biosci. 11:35–40 (1987).CrossRefGoogle Scholar
  14. 14.
    J. T Groves, G. A. McClusky, R. E. White, and M. J. Coon, Aliphatic hydroxylation by highly purified liver microsomal cytochrome P-450. Evidence for a carbon radical intermediate, Biochem. Biophys. Res. Commun. 81:154–160 (1978).PubMedCrossRefGoogle Scholar
  15. 15.
    O. Augusto, H. S. Beilan, and P. R. Ortiz de Montellano, The catalytic mechanism of cytochrome P-450: Spin trapping evidence for one electron substrate oxidation, J. Biol. Chem. 257:11288–11295 (1982).PubMedGoogle Scholar
  16. 16.
    F. F. Kadlubar, K. C. Morton, and D. M. Ziegler, Microsomal-catalyzed hydroperoxide-dependent C-oxidation of amines, Biochem. Biophys. Res. Commun. 54:1255–1261 (1973).PubMedCrossRefGoogle Scholar
  17. 17.
    G. D. Nordblom, R. E. White, and M. J. Coon, Studies on hydroperoxide-dependent substrate hydroxylation by purified liver microsomal cytochrome P-450, Arch. Biochem. Biophys. 175:524–533 (1976).PubMedCrossRefGoogle Scholar
  18. 18.
    R. E. White, S. G. Sligar, and M. J. Coon, Evidence for a homolytic mechanism of peroxide oxygen-oxygen bond cleavage during substrate hydroxylation by cytochrome P-450, J. Biol. Chem. 255:11108–11111 (1980).PubMedGoogle Scholar
  19. 19.
    R. C. Blake II and M. J. Coon, On the mechanism of action of cytochrome P-450. Evaluation of homolytic and heterolytic mechanisms of oxygen-oxygen bond cleavage during substrate hydroxylation by peroxides, J. Biol. Chem. 256:12127–12133 (1981).PubMedGoogle Scholar
  20. 20.
    A. D. N. Vaz and M. J. Coon, NADPH Oxidation by hydroperoxides: Catalysis by cytochrome P-450 and evidence for homolytic cleavage of the peroxide bond, in: “Cytochrome P-450, Biochemistry, Biophysics and Induction,” L. Vereczkey, and K. Magyar, eds., Elsevier, Amsterdam, and Akademiai Kiado, Budapest (1985).Google Scholar
  21. 21.
    A. D. N. Vaz and M. J. Coon, Hydrocarbon formation in the reductive cleavage of hydroperoxides by cytochrome P-450, Proc. Natl. Acad. Sci. USA 84:1172–1176 (1987).PubMedCrossRefGoogle Scholar
  22. 22.
    P. Neta, M. Dizdaroglu, and M. G. Simic, Radiolytic studies of cumyloxyl radicals in aqueous solutions, Isr. J. Chem. 24:25–28 (1984).Google Scholar
  23. 23.
    A. D. N. Vaz and M. J. Coon, Cytochrome P-450-catalyzed reductiverearrangement of hydroperoxides: Isozyme specificity and mechanistic similarity, Fed. Proc. 46:1956 (1987).Google Scholar

Copyright information

© Plenum Press, New York 1988

Authors and Affiliations

  • Alfin D. N. Vaz
    • 1
  • Elizabeth S. Roberts
    • 1
  • Minor J. Coon
    • 1
  1. 1.Department of Biological Chemistry, Medical SchoolThe University of MichiganAnn ArborUSA

Personalised recommendations