The Heme Protein P-450 in Oxygen Activation: Carbon Monoxide Inhibition and Photochemical Action Spectroscopy as Tools to Study Its Catalytic Role

  • Heinz Schleyer
  • Stuart Hamill
  • David Y. Cooper
  • Otto Rosenthal
Part of the Advances in Experimental Medicine and Biology book series (AEMB)

Abstract

Complex membrane-bound multienzyme systems such as the ones located in the endoplasmic reticulum (ER) of liver and other organs or those located predominantly in the inner membranes of the mitochondria of endocrine organs catalyze a variety of oxygenating processes which operate on many different endogenous (e.g. steroids, bile acids) as well as foreign compounds (e.g. drugs, pesticides, toxic chemicals, chemical carcinogens, and other xenobiotics). Atmospheric oxygen, O2, and reducing equivalents, provided by reduced pyridine nucleotides, are co-substrates in these reactions in which, in a formal sense, one or both of the atoms of the oxygen molecule are inserted into the reaction products (monooxygenation and dioxygenation, respectively).

Keywords

Active Oxygen Monochromatic Light Heme Protein Photochemical Action Microsomal Preparation 
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.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Conney, A.H., Levin, W., Ikeda, M., Kuntzman, R., Cooper,D.Y., and Rosenthal, 0., 1968, Inhibitory Effect of Carbon Monoxide on the Hydroxylation of Testosterone by Rat Liver Microsomes, J. Biol. Chem., 243: 3912.PubMedGoogle Scholar
  2. Cooper, D.Y., Levin, S., Narasimhulu, S., Rosenthal, O., and Estabrook, R.W., 1966, Photochemical Action Spectrum of the Terminal Oxidase of Mixed Function Oxidase Systems, Science, 147, 400.CrossRefGoogle Scholar
  3. Cooper, D.Y., Schleyer, H., Vars, H.M., Cannon, M.D., Thomas, J.H., and Rosenthal, 0., 1975, Comparison of the Induction Course, Biophysical - Chemical Interactions and Photochemical Action Spectra of Phenobarbital - and 3-Methylcholanthrene - Induced Hepatic Microsomes, In: “Cytochromes P-450 and b5. Structure, Function, and Interaction”, Cooper, Rosenthal, Snyder, Witmer, eds., Advances in Experimental Medicine and Biology Series, Plenum Press, New York.Google Scholar
  4. Cooper, D.Y., Schleyer, H., Rosenthal, O., Levin, W., Lu, A.Y.H., Kuntzman, R., and Conney, A.H., 1977, Inhibition of CO of Hepatic Benzo[a] pyrene Hydroxylation and its Reversal by Monochromatic Light, Europ.J.Biochem., 74, 69–75.Google Scholar
  5. Cooper, D.Y., Schleyer, H., Levin, S., Eisenhardt, R.H., Novack,B.G., and Rosenthal, 0., 1979, A Reevaluation of the Role of Cytochrome P-450 as the Terminal Oxidase in Hepatic Microsomal Mixed Function Oxidase Catalyzed Reactions, Drug Metabolism Reviews, 10 (2), 153–185.Google Scholar
  6. Estabrook, R.W., Cooper, D.Y., and Rosenthal, 0., 1963, The Light Reversible Carbon Monoxide Inhibition of the Steroid C21-Hydroxylase System of the Adrenal Cortex, Biochem. Z., 338, 741–755.Google Scholar
  7. Franklin, M.R., (1971) The Enzymatic Formation of a Methylenedioxyphenyl Derivative Exhibiting an Isocyanide-like Spectrum with Reduced Cytochrome P-450 in Hepatic Microsomes, Xenobiotica, 1, 581.PubMedCrossRefGoogle Scholar
  8. Greenlee, W.F. and Poland, A., 1978, An Improved Assay of 7-Ethoxycoumarin 0-Deethylase Activity: Induction of Hepatic Enzyme Activity in C57BL/6J and DBA/2J Mice by Phenobarbital, 3-Methyicholanthrene and 2,3,7,8 -Tetrachlorodibenzo-P-dioxin, J.Pharmacol. Exp. Ther., 205, 596–605.Google Scholar
  9. Gunsalus, T.C., Meeko, J.R., Lipscomb, J.D., Debrunner, P. and Munck, E., 1974; In: “Molecular Mechanisms of Oxygen Activation”, 0. Hayaishi, ed., Academic Press, New York.Google Scholar
  10. Rosenthal, O., and Cooper, D.Y., 1967, Methods of Determining the Photochemical Action Spectrum, In: “Methods in Enzymology”, Vol. 10, R.W. Estabrook and M.E. Pullman, volume eds., (Colowick and Kaplan, series eds.), Academic, New York.Google Scholar
  11. Rosenthal, O., Vars, H.M., Schleyer, H., Cooper, D.Y., Levin, S.S., and Touchstone, J., 1977, Induction of Cytochrome P-450 by Long-term Infusion of Phenobarbital, In: “Microsomes and Drug Oxidations”, V.Ullrich, I. Roots, A. Hildebrandt, R. Estabrook, and A.H. Conney, eds., Pergamon Press, Oxford.Google Scholar
  12. Schenkman, J.B., Remmer, H., and Estabrook, R.W., 1967, Spectral Studies of Drug Interaction with Hepatic Microsomal Cytochrome, Mol. Pharmacol. 3, 113–123.Google Scholar
  13. Schleyer, H., Cooper, D.Y., Rosenthal, O., and Cheung, P., 1977, The Heme Protein P-450 from Adrenal Cortex: Its Reactivities in Ferric and Ferrous Forms, Croat. Chem. Acta, 49(2) 179–206.Google Scholar
  14. Schleyer, H., Cooper, D.Y., Rosenthal, O., and Cheung, P., 1979, Photochemical Action Spectroscopy of the Heme Protein P-450 in Soluble and Membrane-bound Monooxygenation Systems, Biophysical J., 25, (2, part2), 129a.Google Scholar
  15. Taube, H., 1965, “Oxygen: Chemistry, Structure and Excited States”, Little and Brown, Boston.Google Scholar
  16. Werringloer, J., Estabrook, R.W., 1979, The Characterization of Product Adducts of Liver Microsomal Cytochrome P-450 and Their Use as Probes for the Heterogeneity of Cytochrome P-450 as Modified by the Induction of Drug Metabolism, In: “The Induction of Drug Metabolism”, R.W. Estabrook and E. Lindelaub, eds., F.K. Schattauer Verlag, Stuttgart.Google Scholar

Copyright information

© Springer Science+Business Media New York 1982

Authors and Affiliations

  • Heinz Schleyer
    • 1
  • Stuart Hamill
    • 1
  • David Y. Cooper
    • 1
  • Otto Rosenthal
    • 1
  1. 1.Departments of Surgery and Pharmacology and the Johnson Research FoundationUniversity of Pennsylvania, School of MedicinePhiladelphiaUSA

Personalised recommendations