Advertisement

Possible Mechanism of Coupled NADPH Oxidase and P-450 Monooxygenase Action

  • Ingela Jansson
  • John B. Schenkman
Part of the Advances in Experimental Medicine and Biology book series (AEMB)

Abstract

Studies on the role of cytochrome b 5 in the hepatic microsomal P-450 mediated mixed function oxidase reaction have shown this hemoprotein to clearly be an intermediate in the NADH-supported electron transfer pathway (Sasame et al., 1973; Hrycay and Prough, 1974; Hrycay and Estabrook, 1974; Lu et al., 1974; Jansson and Schenkman 1975, 1977). Less clear is the role of cytochrome b 5 in the NADPH-supported and NADH-synergized reactions. This synergism has been shown to require cytochrome b 5 by the use of antibodies (Sasame et al., 1973, Mannering et al., 1974, Jansson and Schenkman, 1977), but the mechanism has remained to be elucidated.

Keywords

Xanthine Oxidase Liver Microsome Pyridine Nucleotide Mixed Function Oxidase Reconstituted System 
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. Baron, J., Hildebrandt, A. G., Peterson, J. A., and Estabrook, R. W. (1973). The role of oxygenated cytochrome P-450 and of cytochrome b5 in hepatic microsomal drug oxidations. Drug Metab. Disp., 1, 129–138.Google Scholar
  2. Cinti, D. L., Moldeus, P., and Schenkman, J. B., (1972). Kinetic parameters of drug-metabolizing enzymes in Ca2+ -sedimented microsomes from rat liver. Biochem. Pharmacol. 21, 3249–3256.Google Scholar
  3. Cohen, B. S., and Estabrook, R. W. (1971). Microsomal electron transport reactions II. The use of reduced triphosphopyridine nucleotide and/or reduced diphosphopyridine nucleotide for the oxidative N-demethylation of aminopyrine and other drug substrates. Arch. Biochem. Biophys. 143, 46–53.Google Scholar
  4. Cohen, B. S., and Estabrook, R. W. (1971). Microsomal electron transport reactions III. Cooperative interactions between reduced diphosphopyridine nucleotide and reduced triphosphopyridine nucleotide linked reactions. Arch. Biochem. Biophys. 143, 54–65.Google Scholar
  5. Denk, H., Eckerstorfer, R.,ailcott, R. E., and Schenkman, J. B., (1977). Alteration of hepatic microsomal enzymes by griseofulvin treatment of mice. Biochem. Pharmacol. 26, 1125–1130.Google Scholar
  6. Guengerich, F. P., Ballou, D. P., and Coon, M. J., (1976). Spectral intermediates in the reaction of oxygen with purified liver microsomal cytochrome P-450. Biochem. Biophys. Res. Commun. 70, 951–956.Google Scholar
  7. Hildebrandt, A. G., and Estabrook, R. W. (1971). Evidence for the participation of cytochrome b5 in hepatic microsomal mixed-function oxidation reactions. Arch. Biochem. Biophys. 143, 66–79.Google Scholar
  8. Hildebrandt, A. G., Heinemeyer, G., Nigam, S., and Roots, I., (1980). Substrate and oxygen activation during hexobarbital metabolism, in: Microsomes, Drug Oxidations, and Chemical nrcinogenesis, Coon, et al., Eds., Volume I, pp. 335–338, Academic Press, NY.Google Scholar
  9. Hildebrandt, A. G., and Roots, I., (1975). Reduced nicotinamide adenine dinucleotide phosphate (NADPH)-dependent formation and breakdown of hydrogen peroxide during mixed function oxidation reactions in liver microsomes. Arch. Biochem. Biophys. 171, 385–397.Google Scholar
  10. Hildebrandt, A. G., Speck, M., and Roots I., (1973). Possible control of hydrogen peroxide production and degradation in microsomes during mixed function oxidation reaction. Biochem. Biophys. Res. Commun. 54, 968–975.Google Scholar
  11. Hrvcay, E. G., and Estabrook, R. W., (1974T. The effect of extra bound cytochrome b5 on cytochrome P-450-dependent enzyme activities in liver microsomes. Biochem. Biophys. Res. Commun. 60, 771–778.Google Scholar
  12. Hrycay, E. G., and Prough, R. A., (1974). Reduced nicotinamide adenine dinucleotide-cytochrome b5 reductase and cytochrome b5 as electron carriers in NADH-supported cytochrome P-450 -dependent enzyme activities in liver microsomes. Arch. Biochem. Biophys. 165, 331–339.Google Scholar
  13. Imai, Y., and Sato, R., (1977). The roles of cytochrome b5 in a reconstituted N-demethylase system containing cytochrome P-450. Biochem. Biophys. Res. Commun. 75, 420–426.Google Scholar
  14. Jansson, I., and Schenkman, J. B., (1973). Evidence against participation of cytochrome b5 in the hepatic microsomal mixed-function oxidase reaction. Mol. Pharmacol. 9, 840–845.Google Scholar
  15. Jansson, I., and Sche Tkman, J. B., (1975). Studies on three microsomal electron transfer enzyme systems. Effects of alteration of component enzyme levels in vivo and in vitro. Mol. Pharmacol. 11, 450–461.Google Scholar
  16. Jansson, I., and Schenkman, J. B.,71977). Studies on three microsomal electron transfer enzyme systems. Specificity of electron flow pathways. Arch. Biochem. Biophys. 178, 89–107.Google Scholar
  17. Jansson, I., and Schenkman, J. B., (1978). Influences of substrates of different microsomal electron transfer pathways on the oxidation-reduction kinetics of microsomal cytochrome b5. Arch. Biochem. Biophys. 185, 251–261.Google Scholar
  18. Jeffery, E., and Mannering, G., (1980). Benzphetamine-induced H202 generation, in: Microsomes, Drug Oxidations, and Chemical Carc iiogenesis, Coon, et al. Eds., Volume I, pp. 343–346. Academic Press, NY.Google Scholar
  19. Kuthan, H., Tsuji, H., Graf, H., Ullrich, V., Werringloer, J. and Estabrook, R. W. (1978). Generation of superoxide anion as a source of hydrogen peroxide in a reconstituted monooxygenase system. FEBS. Lett. 91, 343–345.Google Scholar
  20. Lu, A. Y. H., Levin, W., Selander, H., and Jerrina, D.M. (1974). Liver microsomal electron transport systems III. The involvement of cytochrome b5 in the NADPH-supported cytochrome P-450-dependent hydroxylation of chlorobenzene. Biochem. Biophys. Res. Comm. 61, 1348–1355.Google Scholar
  21. Lu, A. Y. H., West, S. B., Vore, M., Ryan, D., and Levin, W. (1974). Role of cytochrome b5 in hydroxylation by a reconstituted cytochrome P-450-containing system. J. Biol. Chem. 249, 6701–6709.Google Scholar
  22. Mannering, G. J., Kuwahara, S., and Omura, T. (1974). Immunochemical evidence for the participation of cytochrome b5 in the NADH synergism of the NADPH-dependent mono-oxidase system of hepatic microsomes. Biochem. Biophys. Res. Comm. 57, 476–481.Google Scholar
  23. McCord, J. M., and Fridovich, I, (1968). The reduction of cytochrome c by milk xanthine oxidase. J. Biol. Chem. 243, 5753–5760.Google Scholar
  24. Netter, K.7, and Illing, H. P. A., (1974). Kinetic experiments on the synergistic effect of NADH on microsomal drug oxidation. Xenobiotica 4, 549–561.CrossRefGoogle Scholar
  25. Nordblom, G. D., White, R. E., and Coon, M. J., (1976). Studies on hydroperoxide-dependent substrate hydroxylation by purified liver microsomal cytochrome P-450. Arch. Biochem. Biophys. 175, 524–533.Google Scholar
  26. Noshiro, M., Harada, N., and— ura, T., (1979). Immunochemical study on the participation of cytochrome b5 in drug oxidation reactions of mouse liver microsomes. Biochem. Biophys. Res. Comm. 91, 207–213.Google Scholar
  27. Poupko, R., and Rosenthal, I. 7973). Electron transfer interactions between superoxide ion and organic compounds. J. Phys. Chem. 77, 1722–1724.Google Scholar
  28. Powis, G., and Jansson, I., (1979). atoichiometry of the mixed function oxidase. Pharmac. Ther. 7, 297–311.Google Scholar
  29. Sasame, H. A., Mitchell, J. R., Thorgeirsson, S., and Gillette, J. R., (1973). Relationship between NADH and NADPH oxidation during drug metabolism. Drug Metab. Disp. 1, 150–155.Google Scholar
  30. Sasame, H. A., Thorgeirsson, S. S., Mitchell, J. R., and Gillette, J. R., (1974). The possible involvement of cytochrome b5 in the oxidation of lauric acid by microsomes from kidney cortex and liver of rats. Life Sci. 14, 35–46.PubMedCrossRefGoogle Scholar
  31. Schenkman, J. B., Jansson, I., Powis, G., and Kappus, H. (1979). Active oxygen in liver microsomes: Mechanism of epinephrine oxidation. Mol. Pharmacol. 15, 428–438.Google Scholar
  32. Schenkman, J. B., Janssen, I., and Robie-Suh, K. M., (1976). The many roles of cytochrome b5 in hepatic microsomes. Life Sci. 19, 611–624.PubMedCrossRefGoogle Scholar
  33. Sligar, S. G., Cinti, D. L., Gibson, G. G., and Schenkman, J. B., (1979). Spin state control of the hepatic cytochrome P-450 redox potential. Biochem. Biophys. Res. Commun. 90, 925–932.Google Scholar
  34. Staudt, H., Lichtenberger, F., and Ullrich, V., (1974). The role of NADH in uncoupled microsomal monoxygenations. Eur. J. Biochem. 46, 99–106.Google Scholar
  35. Sugiyama, T., Miki, N., and Yamano, T., (1979). The obligatory requirement of cytochrome b5 in the p-nitroanisole 0-demethylation reaction catalyzed by cytochrome P-450 with a high affinity for cytochrome b5. Biochem. Biophys. Res. Commun. 90, 715–720.Google Scholar
  36. Wilshire, J., and Sawyer, D. T.,Ç1979). Redox Chemistry of dioxygen species, Accounts of Chemical Research, 12, 105–110.Google Scholar

Copyright information

© Springer Science+Business Media New York 1982

Authors and Affiliations

  • Ingela Jansson
    • 1
  • John B. Schenkman
    • 1
  1. 1.University of Connecticut Health CenterFarmingtonUSA

Personalised recommendations