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Inhibition of Cytochrome P-450 Enzymes

  • Chapter
Cytochrome P-450

Abstract

The catalytic cycle of cytochrome P-450 (see Chapter 7) traverses three steps that are particularly vulnerable to inhibition: (1) the binding of substrates, (2) the binding of molecular oxygen subsequent to the first electron transfer, and (3) the catalytic step in which the substrate is actually oxidized. This chapter focuses on inhibitors that act at one of these three steps. Inhibitors that act at other steps in the catalytic cycle, such as quinones that interfere with the electron supply to the hemeprotein by accepting electrons directly from cytochrome P-450 reductase,1–3 are not discussed here.

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References

  1. Rahimtula, A. D., and O’Brien, P. J., 1977, The peroxidase nature of cytochrome P450, in: Microsomes and Drug Oxidations ( V. Ullrich, I. Roots, A. Hildebrandt, R. W. Estabrook, and A. H. Conney, eds.), Pergamon Press, Elmsford, N.Y., pp. 210–217.

    Google Scholar 

  2. Yang, C. S., and Strickhart, F. S., 1974, Inhibition of mixed function oxidase activity by propylgallate, Biochem. Pharmacol. 23: 3129–3138.

    Article  PubMed  CAS  Google Scholar 

  3. Cummings, S. W., and Prough, R. A., 1983, Butylated hydroxyanisole-stimulated NADPH oxidase activity in rat liver microsomal fractions, J. Biol. Chem. 258: 12315–12319.

    PubMed  CAS  Google Scholar 

  4. Testa, B., and Jenner, P., 1981, Inhibitors of cytochrome P-450s and their mechanism of action, Drug. Metab. Rev. 12: 1–117.

    Article  PubMed  CAS  Google Scholar 

  5. Netter, K. J., 1980, Inhibition of oxidative drug metabolism in microsomes, Pharmacol. Ther. A 10: 515–535.

    CAS  Google Scholar 

  6. Sato, A., and Nakajima, T., 1979, Dose-dependent metabolic interaction between benzene and toluene in vivo and in vitro, Toxicol. Appl. Pharmacol. 48: 249–256.

    Article  PubMed  CAS  Google Scholar 

  7. Jefcoate, C. R., 1978, Measurement of substrate and inhibitor binding to microsomal cytochrome P-450 by optical-difference spectroscopy, Methods Enzymol. 52: 258–279.

    Article  PubMed  CAS  Google Scholar 

  8. Kumaki, K., Sato, M., Kon, H., and Nebert, D. W., 1978, Correlation of type I, type II, and reverse type I difference spectra with absolute changes in spin state of hepatic microsomal cytochrome P-450 iron from five mammalian species, J. Biol. Chem. 253: 1048–1058.

    PubMed  CAS  Google Scholar 

  9. Schenkman, J. B., Sligar, S. G., and Cinti, D. L., 1981, Substrate interactions with cytochrome P-450, Pharmacol. Ther. 12: 43–71.

    Article  PubMed  CAS  Google Scholar 

  10. 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.

    Article  PubMed  CAS  Google Scholar 

  11. Guengerich, F. P., 1983, Oxidation—reduction properties of rat liver cytochromes P450 and NADPH-cytochrome P-450 reductase related to catalysis in reconstituted systems, Biochemistry 22: 2811–2820.

    Article  PubMed  CAS  Google Scholar 

  12. Kitada, M., Chiba, K., Kamataki, T., and Kitagawa, H., 1977, Inhibition by cyanide of drug oxidations in rat liver microsomes, Jpn. J. Pharmacol. 27: 601–608.

    Article  PubMed  CAS  Google Scholar 

  13. Ho, B., and Castagnoli, N., 1980, Trapping of metabolically generated electrophilic species with cyanide ion: Metabolism of 1-benzylpyrrolidine, J. Med. Chem. 23: 133–139.

    Article  PubMed  CAS  Google Scholar 

  14. Sono, M., and Dawson, J. H., 1982, Formation of low spin complexes of ferric cytochrome P-450-CAM with anionic ligands: Spin state and ligand affinity comparison to myoglobin, J. Biol. Chem. 257: 5496–5502.

    PubMed  CAS  Google Scholar 

  15. Backes, W. L., Hogaboom, M., and Canady, W. J., 1982, The true hydrophobicity of microsomal cytochrome P-450 in the rat: Size dependence of the free energy of binding of a series of hydrocarbon substrates from the aqueous phase to the enzyme and to the membrane as derived from spectral binding data, J. Biol. Chem. 257: 4063–4070.

    PubMed  CAS  Google Scholar 

  16. Omura, T., and Sato, R., 1964, The carbon monoxide-binding pigment of liver microsomes. I. Evidence for its hemoprotein nature, J. Biol. Chem. 239: 2370–2378.

    PubMed  CAS  Google Scholar 

  17. Coltman, J. P., and Sorrell, T. N., 1975, A model for the carbonyl adduct of ferrous cytochrome P-450, J. Am. Chem. Soc. 97: 4133–4134.

    Article  Google Scholar 

  18. Canick, J. A., and Ryan, K. J., 1976, Cytochrome P-450 and the aromatization of 16alpha-hydroxytestosterone and androstenedione by human placental microsomes, Mol. Cell. Endocrinol. 6: 105–115.

    Article  PubMed  CAS  Google Scholar 

  19. Gibbons, G. F., Pullinger, C. R., and Mitropoulos, K. A., 1979, Studies on the mechanism of lanosterol 14-alpha-demethylation: A requirement for two distinct types of mixed-function-oxidase systems, Biochem. J. 183: 309–315.

    PubMed  CAS  Google Scholar 

  20. Hanson, L. K., Eaton, W. A., Sligar, S. G., Gunsalus, I. C., Gouterman, M., and Connell, C. R., 1976, Origin of the anomalous Soret spectra of carboxycytochrome P450, J. Am. Chem. Soc. 98: 2672–2674.

    Article  PubMed  CAS  Google Scholar 

  21. Cohen, G. M., and Mannering, G. J., 1972, Involvement of a hydrophobic site in the inhibition of the microsomal para-hydroxylation of aniline by alcohols, Mol. Pharmacol. 8: 383–397.

    Google Scholar 

  22. Testa, B., 1981, Structural and electronic factors influencing the inhibition of aniline hydroxylation by alcohols and their binding to cytochrome P-450, Chem. Biol. Interact. 34: 287–300.

    Article  PubMed  CAS  Google Scholar 

  23. Wattenberg, L. W., Lam, L. K. T., and Fladmoe, A. V., 1979, Inhibition of chemical carcinogen-induced neoplasia by coumarins and alpha-angelicalactone, Cancer Res. 39: 1651–1654.

    PubMed  CAS  Google Scholar 

  24. Remmer, H., Schenkman, J., Estabrook, R. W., Sasame, H., Gillette, J., Narasimhulu, S., Cooper, D. Y., and Rosenthal, 0., 1966, Drug interaction with hepatic microsomal cytochrome, Mol. Pharmacol. 2: 187–190.

    PubMed  CAS  Google Scholar 

  25. Jefcoate, C. R., Gaylor, J. L., and Callabrese, R. L., 1969, Ligand interactions with cytochrome P-450. I. Binding of primary amines, Biochemistry 8: 3455–3463.

    Article  PubMed  CAS  Google Scholar 

  26. Schenkman, J. B., Remmer, H., and Estabrook, R. W., 1967, Spectral studies of drug interaction with hepatic mircrosomal cytochrome P-450, Mol. Pharmacol. 3: 113–123.

    PubMed  CAS  Google Scholar 

  27. Dominguez, O. V., and Samuels, L. T., 1963, Mechanism of inhibition of adrenal steroid 11-beta-hydroxylase by methopyrapone (metopirone), Endocrinology 73: 304–309.

    Article  PubMed  CAS  Google Scholar 

  28. Temple, T. E., and Liddle, G. W., 1970, Inhibitors of adrenal steroid biosynthesis, Annu. Rev. Pharmacol. 10: 199–218.

    Article  PubMed  CAS  Google Scholar 

  29. Rogerson, T. D., Wilkinson, C. F., and Hetarski, K., 1977, Steric factors in the inhibitory interaction of imidazoles with microsomal enzymes, Biochem. Pharmacol. 26: 1039–1042.

    Article  PubMed  CAS  Google Scholar 

  30. Wilkinson, C. F., Hetarski, K., Cantwell, G. P., and DiCarlo, F. J., 1974, Structure—activity relationships in the effects of 1-alkylimidazoles on microsomal oxidation in vitro and in vivo, Biochem. Pharmacol. 23: 2377–2386.

    Article  PubMed  CAS  Google Scholar 

  31. Foster, A. B., Jarman, M., Leung, C.-S., Rowlands, M. G., and Taylor, G. N., 1983, Analogues of aminoglutethimide: Selective inhibition of cholesterol side-chain cleavage, J. Med. Chem. 26: 50–54.

    Article  PubMed  CAS  Google Scholar 

  32. Foster, A. B., Jarman, M., Leung, C.-S., Rowlands, M. G., Taylor, G. N., Plevey, R. G., and Sampson, P., 1985, Analogues of aminoglutethimide: Selective inhibition of aromatase, J. Med. Chem. 28: 200–204.

    Article  PubMed  CAS  Google Scholar 

  33. Hays, S. J., Tobes, M. C., Gildersleeve, D. L., Wieland, D. M., and Beierwaltes, W. H., 1984, Structure-activity relationship study of the inhibition of adrenal cortical 11beta-hydroxylase by new metyrapone analogues, J. Med. Chem. 27: 15–19.

    Article  PubMed  CAS  Google Scholar 

  34. Lesca, P., Rafidinarino, E., Lecointe, P., and Mansuy, D., 1979, A class of strong inhibitors of microsomal monooxygenases: The ellipticines, Chem. Biol. Interact. 24: 189–198.

    Article  PubMed  CAS  Google Scholar 

  35. Walsh, C., 1982, Suicide substrates: Mechanism-based enzyme inactivators, Tetrahedron 38: 871–909.

    Article  CAS  Google Scholar 

  36. Santi, D. V., and Kenyon, G. L., 1980, Approaches to the rational design of enzyme inhibitors, in: Burger’s Medicinal Chemistry, 4th ed., Part 1, Wiley—Interscience, New York, pp. 349–391.

    Google Scholar 

  37. Dalvi, R. R., Poore, R. E., and Neal, R. A., 1974, Studies of the metabolism of carbon disulphide by rat liver microsomes, Life Sci. 14: 1785–1796.

    Article  PubMed  CAS  Google Scholar 

  38. De Matteis, F. A., and Seawright, A. A., 1973, Oxidative metabolism of carbon disulphide by the rat: Effect of treatments which modify the liver toxicity of carbon disulphide, Chem. Biol. Interact. 7: 375–388.

    Article  PubMed  Google Scholar 

  39. Bond, E. J., and De Matteis, F. A., 1969, Biochemical changes in rat liver after administration of carbon disulphide, with particular reference to microsomal changes, Biochem. Pharmacol. 18: 2531–2549.

    Article  PubMed  CAS  Google Scholar 

  40. Halpert, J., Hammond, D., and Neal, R. A., 1980, Inactivation of purified rat liver cytochrome P-450 during the metabolism of parathion (diethyl p-nitrophenyl phosphorothionate), J. Biol. Chem. 255: 1080–1089.

    PubMed  CAS  Google Scholar 

  41. Neal, R. A., Kamataki, T., Lin, M., Ptashne, K. A., Dalvi, R., and Poore, R. Y., 1977, Studies of the formation of reactive intermediates of parathion, in: Biological Reactive Intermediates ( D. J. Jollow, J. J. Koesis, R. Snyder, and H. Vaino, eds.), Plenum Press, New York, pp. 320–332.

    Chapter  Google Scholar 

  42. Miller, G. E., Zemaitis, M. A., and Greene, F. E., 1983, Mechanisms of diethyldithiocarbamate-induced loss of cytochrome P-450 from rat liver, Biochem. Pharmacol. 32: 2433–2442.

    Article  PubMed  CAS  Google Scholar 

  43. El-hawari, A. M., and Plaa, G. L., 1979, Impairment of hepatic mixed-function oxidase activity by alpha-and beta-naphthylisothiocyanate: Relationship to hepatotoxicity, Toxicol. Appt. Pharmacol. 48: 445–458.

    Article  CAS  Google Scholar 

  44. Lee, P. W., Arnau, T., and Neal, R. A., 1980, Metabolism of alpha-naphthylthiourea by rat liver and rat lung microsomes, Toxicol. Appt. Pharmacol. 53: 164–173.

    Article  CAS  Google Scholar 

  45. Menard, R. H., Guenthner, T. M., Taburet, A. M., Kon, H., Pohl, L. R., Gillette, J. R., Gelboin, H. V., and Trager, W. F., 1979, Specificity of the in vitro destruction of adrenal and hepatic microsomal steroid hydroxylases by thiosterols, Mol. Pharmacol. 16: 997–1010.

    PubMed  CAS  Google Scholar 

  46. Halpert, J., and Neal, R. A., 1980, Inactivation of purified rat liver cytochrome P-450 by chloramphenicol, Mol. Pharmacol. 17: 427–434.

    PubMed  CAS  Google Scholar 

  47. Halpert, J., 1982, Further studies of the suicide inactivation of purified rat liver cytochrome P-450 by chloramphenicol, Mol. Pharmacol. 21: 166–172.

    PubMed  CAS  Google Scholar 

  48. Halpert, J., 1981, Covalent modification of lysine during the suicide inactivation of rat liver cytochrome P-450 by chloramphenicol, Biochem. Pharmacol. 30: 875–881.

    Article  PubMed  CAS  Google Scholar 

  49. Halpert, J., Naslund, B., and Betner, I., 1983, Suicide inactivation of rat liver cytochrome P-450 by chloramphenicol in vivo and in vitro, Mol. Pharmacol. 23: 445–452.

    PubMed  CAS  Google Scholar 

  50. Kagawa, C. M., 1960, Blocking the renal electrolyte effects of mineralcorticoids with an orally active steroidal spirolactone, Endocrinology 67: 125–132.

    Article  PubMed  CAS  Google Scholar 

  51. Saunders, F. J., and Alberti, R. L., 1978, Aldactone: Spironolactone: A Comprehensive Review, Searle, New York.

    Google Scholar 

  52. Menard, R. H., Guenthner, T. M., Kon, H., and Gillette, J. R., 1979, Studies on the destruction of adrenal and testicular cytochrome P-450 by spironolactone: Requirement for the 7-alpha-thio group and evidence for the loss of the heure and apoproteins of cytochrome P-450, J. Biol. Chem. 254: 1726–1733.

    Google Scholar 

  53. Stripp, B., Menard, R. H., Zampaglione, N. G., Hamrick, M. E., and Gillette, J. R., 1973, Effect of steroids on drug metabolism in male and female rats, Drug. Metab. Dispos. 1: 216–221.

    PubMed  CAS  Google Scholar 

  54. Hamrick, M. E., Zampaglione, N. G., Stripp, B., and Gillette, J. R., 1973, Investigation of the effects of methyltestosterone, cortisone, and spironolactone on the hepatic microsomal mixed function oxidase system in male and female rats, Biochem. Pharmacol. 22: 293–310.

    Article  PubMed  CAS  Google Scholar 

  55. Casida, J. E., 1970, Mixed function oxidase involvement in the biochemistry of insecticide synergists, J. Agr. Food Chem. 18: 753–772.

    Article  CAS  Google Scholar 

  56. Hodgson, E., and Philpot, R. M., 1974, Interaction of methylene dioxyphenol (1,3benzodioxole) compounds with enzymes and their effects on mammals, Drug Metab. Rev. 3: 231–301.

    Article  PubMed  CAS  Google Scholar 

  57. Wilkinson, C. F., Murray, M., and Marcus, C. B., 1984, Interactions of methylenedioxyphenyl compounds with cytochrome P-450 and effects on microsomal oxidation, in: Reviews in Biochemical Toxicology, Volume 6 (E. Hodgson, J. R. Bend, and R. M. Philpot, eds.), Elsevier, Amsterdam, pp. 27–63.

    Google Scholar 

  58. Kulkarni, A. P., and Hodgson, E., 1978, Cumene hydroperoxide-generated spectral interactions of piperonyl butoxide and other synergists with microsomes from mammals and insects, Pestic. Biochem. Physiol. 9: 75–83.

    Article  CAS  Google Scholar 

  59. Franklin, M. R., 1971, The enzymic formation of a methylene dioxyphenyl derivative exhibiting an isocyanide-like spectrum with reduced cytochrome P-450 in hepatic microsomes, Xenobiotica 1: 581–591.

    Article  PubMed  CAS  Google Scholar 

  60. Elcombe, C. R., Bridges, J. W., Nimmo-Smith, R. H., and Werringloer, J., 1975, Cumene hydroperoxide-mediated formation of inhibited complexes of methylenedioxyphenyl compounds with cytochrome P-450, Biochem. Soc. Trans. 3: 967–970.

    CAS  Google Scholar 

  61. Elcombe, C. R., Bridges, J. W., Gray, T. J. B., Nimmo-Smith, R. H., and Netter, K. J., 1975, Studies on the interaction of safrole with rat hepatic microsomes, Biochem. Pharmacol. 24: 1427–1433.

    Article  CAS  Google Scholar 

  62. Dickins, M., Elcombe, C. R., Moloney, S. J., Netter, K. J., and Bridges, J. W., 1979, Further studies on the dissociation of the isosafrole metabolite—cytochrome P-450 complex, Biochem. Pharmacol. 28: 231–238.

    Article  PubMed  CAS  Google Scholar 

  63. Ullrich, V., and Schnabel, K. H., 1973, Formation and binding of carbanions by cytochrome P-450 of liver microsomes, Drug Metab. Dispos. 1:176–183.

    Google Scholar 

  64. Ullrich, V., 1977, Mechanism of microsomal monooxygenases and drug toxicity, in: Biological Reactive Intermediates ( D. J. Jollow, J. Kocsis, R. Snyder, and H. Vaino, eds.), Plenum Press, New York, pp. 65–82.

    Chapter  Google Scholar 

  65. Murray, M., Wilkinson, C. F., Marcus, C., and Dube, C. E., 1983, Structure—activity relationships in the interactions of alkoxymethylenedioxybenzene derivatives with rat hepatic microsomal mixed-function oxidases in vivo, Mol. Pharmacol. 24: 129–136.

    PubMed  CAS  Google Scholar 

  66. Mansuy, D., 1981, Use of model systems in biochemical toxicology: Herne models, in: Reviews in Biochemical Toxicology, Volume 3, ( E. Hodgson, J. R. Bend, and R. M. Philpot, eds.), Elsevier, Amsterdam, pp. 283–320.

    Google Scholar 

  67. Mansuy, D., Battioni, J. P., Chottard, J. C., and Ullrich, V., 1979, Preparation of a porphyrin-iron-carbene model for the cytochrome P-450 complexes obtained upon metabolic oxidation of the insecticide synergists of the 1,3-benzodioxole series, J. Am. Chem. Soc. 101: 3971–3973.

    Article  CAS  Google Scholar 

  68. Dahl, A. R., and Hodgson, E., 1979, The interaction of aliphatic analogs of methylenedioxyphenyl compounds with cytochromes P-450 and P-420, Chem. Biol. Interact. 27: 163–175.

    Article  PubMed  CAS  Google Scholar 

  69. Anders, M. W., Sunram, J. M., and Wilkinson, C. F., 1984, Mechanism of the metabolism of 1,3-benzodioxoles to carbon monoxide, Biochem. Pharmacol. 33: 577–580.

    Article  PubMed  CAS  Google Scholar 

  70. Hansch, C., 1968, The use of homolytic, steric, and hydrophobic constants in a structure—activity study of I,3-benzodioxole synergists, J. Med. Chem. 11: 920–924.

    Article  PubMed  CAS  Google Scholar 

  71. Hennessy, D. J., 1965, Hydride-transfering ability of methylene dioxybenzenes as a basis of synergistic activity, J. Agr. Food Chem. 13: 218–231.

    Article  CAS  Google Scholar 

  72. Cook, J. C., and Hodgson, E., 1983, Induction of cytochrome P-450 by methylenedioxyphenyl compounds: Importance of the methylene carbon, Toxicol. Appl. Pharmacol. 68: 131–139.

    Article  PubMed  CAS  Google Scholar 

  73. Casida, J. E., Engel, J. L., Essac, E. G., Kamienski, F. X., and Kuwatsuka, S., 1966, Methylene-14C-dioxyphenyl compounds: Metabolism in relation to their synergistic action, Science 153: 1130–1133.

    Article  PubMed  CAS  Google Scholar 

  74. Kamienski, F. X., and Casida, J. E., 1970, Importance of methylenation in the metabolism in vivo and in vitro of methylenedioxyphenyl synergists and related compounds in mammals, Biochem. Pharmacol. 19: 91–112.

    Article  PubMed  CAS  Google Scholar 

  75. Yu, L.-S., Wilkinson, C. F., and Anders, M. W., 1980, Generation of carbon monoxide during the microsomal metabolism of methylenedioxyphenyl compounds, Biochem. Pharmacol. 29: 1113–1122.

    Article  PubMed  CAS  Google Scholar 

  76. Metcalf, R. L., Fukuto, C. W., Fahmy, S.,,EI-Azis, S., and Metcalf, E. R., 1966, Mode of action of carbamate synergists, J. Agr. Food. Chem. 14: 555–562.

    Article  CAS  Google Scholar 

  77. Franklin, M. R., 1977, Inhibition of mixed-function oxidations by substrates forming reduced cytochrome P-450 metabolic-intermediate complexes, Pharmacol. Ther. A 2: 227–245.

    CAS  Google Scholar 

  78. Larrey, D., Tinel, M., and Pessayre, D., 1983, Formation of inactive cytochrome P450 Fe(II)-metabolite complexes with several erythromycin derivatives but not with josamycin and midecamycin in rats, Biochem. Pharmacol. 32: 1487–1493.

    Article  PubMed  CAS  Google Scholar 

  79. Delaforge, M., Jaquen, M., and Mansuy, D., 1983, Dual effects of macrolide antibiotics on rat liver cytochrome P-450. Induction and formation of metabolite-complexes: A structure—activity relationship, Biochem. Pharmacol. 32: 2309–2318.

    Article  PubMed  CAS  Google Scholar 

  80. Mansuy, D., Beaune, P., Cresteil, T., Bacot, C., Chottard, J. C., and Gans, P., 1978, Formation of complexes between microsomal cytochrome P-450-Fe(II) and nitrosoarenes obtained by oxidation of arylhydroxylamines or reduction of nitroarenes in situ, Eur. J. Biochem. 86: 573–579.

    Article  PubMed  CAS  Google Scholar 

  81. Jonsson, J., and Lindeke, B., 1976, On the formation of cytochrome P-450 product complexes during the metabolism of phenylalkylamines, Acta Pharm. Suec. 13: 313–320.

    PubMed  CAS  Google Scholar 

  82. Franklin, M. R., 1974, The formation of a 455 nm complex during cytochrome P-450-dependent N-hydroxylamphetamine metabolism, Mol. Pharmacol. 10: 975–985.

    CAS  Google Scholar 

  83. Muakkasah, S. F., Bidlack, W. R., and Yang, W. C. T., 1981, Mechanism of the inhibitory action of isoniazid on microsomal drug metabolism, Biochem. Pharmacol. 30: 1651–1658.

    Article  Google Scholar 

  84. Mansuy, D., 1978, Coordination chemistry of cytochromes P-450 and iron-porphyrins: Relevance to pharmacology and toxicology, Biochimie 60: 969–977.

    Article  CAS  Google Scholar 

  85. Lindeke, B., Anderson, E., Lundkvist, G., Jonsson, H., and Eriksson, S.-O., 1975, Autoxidation of N-hydroxyamphetamine and N-hydroxyphentermine: The formation of 2-nitroso-l-phenyl-propanes and 1-phenyl-2-propanone oxime, Acta Pharm. Suec. 12: 183–198.

    Google Scholar 

  86. Mansuy, D., Gans, P., Chottard, J.-C., and Bartoli, J.-F., 1977, Nitrosoalkanes as Fe(II) ligands in the 455-nm-absorbing cytochrome P-450 complexes formed from nitroalkanes in reducing conditions, Eur. J. Biochem. 76: 607–615.

    Article  PubMed  CAS  Google Scholar 

  87. Hines, R. N., and Prough, R. A., 1980, The characterization of an inhibitory complex formed with cytochrome P-450 and a metabolite of 1,1-disubstituted hydrazines, J. Pharmacol. Ther. 214: 80–86.

    CAS  Google Scholar 

  88. Moloney, S. J., Snider, B. J., and Prough, R. A., 1984, The interactions of hydrazine derivatives with rat-hepatic cytochrome P-450, Xenobiotica 14: 803–814.

    Article  PubMed  CAS  Google Scholar 

  89. Muakkassah, S. F., Bidlack, W. R., and Yang, W. C. T., 1982, Reversal of the effects of isoniazid on hepatic cytochrome P-450 by potassium ferricyanide, Biochem. Pharmacol. 31: 249–251.

    Article  PubMed  CAS  Google Scholar 

  90. Mahy, J.-P., Battioni; P., Mansuy, D., Fisher, J., Weiss, R., Mispelter, J., Morgenstern-Badarau, I., and Gans, P., 1984, Iron porphyrin-nitrene complexes: Preparation from 1,1-dialkylhydrazines: Electronic structure from NMR, Mossbauer, and the magnetic susceptibility studies and crystal structure of the [tetrakis(p-chlorophenyl) porphyrinatol [(2,2,6,6-tetramethyl-l-piperidyl) nitrene]iron complex,J. Am. Chem. Soc. 106:1699–1706.

    Google Scholar 

  91. Mansuy, D., Battioni, P., and Mahy, J. P., 1982, Isolation of an iron-nitrene complex from the dioxygen and iron porphyrin dependent oxidation of a hydrazine, J. Am. Chem. Soc. 104: 4487–4489.

    Article  CAS  Google Scholar 

  92. Ortiz de Montellano, P. R., 1985, Alkenes and alkynes, in: Bioactivation of Foreign Compounds ( M. Anders, ed.), Academic Press, New York, pp. 121–155.

    Google Scholar 

  93. De Matteis, F., 1978, Loss of liver cytochrome P-450 caused by chemicals, in: Heme and Hemoproteins, Handbook of Experimental Pharmacology, Volume 44 (F. De Matteis and W. N. Aldridge, eds.), Springer-Verlag, Berlin, pp. 95–127.

    Google Scholar 

  94. Ortiz de Montellano, P. R., and Correia, M. A., 1983, Suicidal destruction of cytochrome P-450 during oxidative drug metabolism, Annu. Rev. Pharmacol. Toxicol. 23: 481–503.

    Article  Google Scholar 

  95. Ortiz de Montellano, P. R., and Mico, B. A., 1980, Destruction of cytochrome P-450 by ethylene and other olefins, Mol. Pharmacol. 18: 128–135.

    PubMed  CAS  Google Scholar 

  96. Ortiz de Montellano, P. R., Mangold, B. L. K., Wheeler, C., Kunze, K. L., and Reich, N. 0., 1983, Stereochemistry of cytochrome P-450-catalyzed epoxidation and prosthetic heme alkylation, J. Biol. Chem. 258: 4208–4213.

    CAS  Google Scholar 

  97. Ortiz de Montellano, P. R., Stearns, R. A., and Langry, K. C., 1984, The allylisopropylacetamide and novonal prosthetic heure adducts, Mol. Pharmacol. 25: 310–317.

    PubMed  CAS  Google Scholar 

  98. Ortiz de Montellano, P. R., Kunze, K. L., Beilan, H. S., and Wheeler, C., 1982, Destruction of cytochrome P-450 by vinyl fluoride, fluroxene, and acetylene: Evidence for a radical cation intermediate in olefin oxidation, Biochemistry 21: 1331–1339.

    Article  PubMed  CAS  Google Scholar 

  99. Kunze, K. L., Mangold, B. L. K. Wheeler, C., Beilan, H. S., and Ortiz de Montellano, P. R., 1983, The cytochrome P-450 active site, J. Biol. Chem. 258: 4202–4207.

    CAS  Google Scholar 

  100. Ortiz de Montellano, P. R., and Komives, E. A., 1985, Branchpoint for heme alkylation and metabolite formation in the oxid; f aryl acetylenes, J. Biol. Chem. 260: 3330–3336.

    PubMed  CAS  Google Scholar 

  101. Ortiz de Montellano, P. R., and Kui,…, K. L., 1980, Self-catalyzed inactivation of hepatic cytochrome P-450 by ethynyl substrates, J. Biol. Chem. 255: 5578–5585.

    PubMed  CAS  Google Scholar 

  102. Gan, L. -S. L., Acebo, A. L., and Alworth, W. L., 1984, 1-Ethynylpyrene, a suicide inhibitor of cytochrome P-450 dependent benzo(a)pyrene hydroxylase activity in liver microsomes, Biochemistry 23: 3827–3836.

    Google Scholar 

  103. De Matteis, F., Abbritti, G., and Gibbs, A. H., 1973, Decreased liver activity of porphyrin-metal chelatase in hepatic porphyria caused by 3,5-diethoxycarbonyl-1,4dihydrocollidine: Studies in rats and mice, Biochem J. 134: 717–727.

    PubMed  Google Scholar 

  104. De Matteis, F., and Gibbs, A., 1972, Stimulation of liver 5-aminolaevulinate synthetase by drugs and its relevance to drug-induced accumulation of cytochrome P-450, Biochem. J. 126: 1149–1160.

    PubMed  Google Scholar 

  105. Gayarthri, A. K., and Padmanaban, G., 1974, Biochemical effects of 3,5-diethoxycarbonyl-1,4-dihydrocollidine in mouse liver, Biochem. Pharmacol. 23: 2713–2725.

    Article  Google Scholar 

  106. Tephly, T. R., Gibbs, A. H., Ingall, G., and De Matteis, F., 1980, Studies on the mechanism of experimental porphyria and ferrochelatase inhibition produced by 3,5diethoxycarbonyl-1,4-dihydrocollidine, /nt. J. Biochem. 12: 993–998.

    CAS  Google Scholar 

  107. Cole, S. P. C. C., and Marks, G. S., 1984, Ferrochelatase and N-alkylated porphyrins, Mol. Cell. Biochem. 64: 127–137.

    Article  PubMed  CAS  Google Scholar 

  108. Augusto, O., Beilan, H. S., and Ortiz de Montellano, P. R., 1982, The catalytic mechanism of cytochrome P-450: Spin-trapping evidence for one-electron substrate oxidation, J. Biol. Chem. 257: 11288–11295.

    PubMed  CAS  Google Scholar 

  109. De Matteis, F., Hollands, C., Gibbs, A. H., de Sa, N., and Rizzardini, M., 1982, Inactivation of cytochrome P-450 and production of N-alkylated porphyrins caused in isolated hepatocytes by substituted dihydropyridines: Structural requirements for loss of haem and alkylation of the pyrrole nitrogen atom, FEBS Lett 145: 87–92.

    Article  PubMed  Google Scholar 

  110. Tephly, T. R., Coffman, B. L., Ingall, G., Abou Zeit-Har, M. S., Goff, H. M., Tabba, H. D., and Smith, K. M., 1981, Identification of N-methylprotoporphyrin IX in livers of untreated mice and mice treated with 3,5-diethoxycarbonyl-1,4-dihydrocollidine: Source of the methyl group, Arch. Biochem. Biophys. 212: 120–126.

    Article  PubMed  CAS  Google Scholar 

  111. De Matteis, F., Gibbs, A. H., Farmer, P. B., and Lamb, J. H., 1981, Liver production of N-alkylated porphyrins caused by treatment with substituted dihydropyridines, FEBS Lett. 129: 328–331.

    Article  PubMed  Google Scholar 

  112. Ortiz de Montellano, P. R., and Kerr, D. E., 1985, Inactivation of myoglobin by orthosubstituted aryl hydrazines: Formation of prosthetic heure aryl-iron but not N-aryl adducts, Biochemistry 24: 1147–1152.

    Article  PubMed  CAS  Google Scholar 

  113. De Matteis, F., Gibbs, A. H., and Hollands, C, 1983, N-Alkylation of the haem moiety of cytochrome P-450 caused by substituted dihydropyridines. Preferential attack of different pyrrole nitrogen atoms after induction of various cytochrome P-450 isoenzymes, Biochem. J. 211: 455–461.

    PubMed  Google Scholar 

  114. Lukton, D., and Ortiz de Montellano, P. R., 1985, Oxidative inactivation of cytochrome P-450 by a 2,2-dialkyl-l,2-dihydroquinoline, Fed. Proc. 44: 1399.

    Google Scholar 

  115. Muakkassah, W. F., and Yang, W. C. T., 1981, Mechanism of the inhibitory action of phenelzine on microsomal drug metabolism, J. Pharmacol. Exp. Ther. 219: 147–155.

    PubMed  CAS  Google Scholar 

  116. Ortiz de Montellano, P. R., Augusto, O., Viola, F., and Kunze, K. L., 1983, Carbon radicals in the metabolism of alkyl hydrazines, J. Biol. Chem. 258: 8623–8629.

    PubMed  CAS  Google Scholar 

  117. Jonen, H. G., Werringloer, J., Prough, R. A., and Estabrook, R. W., 1982, The reaction of phenylhydrazine with microsomal cytochrome P-450: Catalysis of heure modification, J. Biol. Chem. 257: 4404–4411.

    PubMed  CAS  Google Scholar 

  118. Mansuy, D., Battioni, P., Bartoli, J.-F., and Mahy, J. -P., 1985, Suicidal inactivation of microsomal cytochrome P-450 by hydrazones, Biochem. Pharmacol. 34: 431–432.

    Article  CAS  Google Scholar 

  119. Ortiz de Montellano, P. R., and Kunze, K. L., 1981, Formation of N-phenylheme in the hemolytic reaction of phenylhydrazine with hemoglobin, J. Am. Chem. Soc. 103: 581–586.

    Article  CAS  Google Scholar 

  120. Saito, S., and Itano, H. A., 1981, Beta-meso-phenylbiliverdin IX-alpha and N-phenylprotoporphyrin IX, products of the reaction fo phenylhydrazine with oxyhemoproteins, Proc. Natl. Acad. Sci. USA 78: 5508–5512.

    Article  PubMed  CAS  Google Scholar 

  121. Augusto, O., Kunze, K. L., and Ortiz de Montellano, P. R., 1982, N-Phenylprotoporphyrin IX formation in the hemoglobin—phenylhydrazine reaction: Evidence for a protein-stabilized iron-phenyl intermediate, J. Biol. Chem. 257: 6231–6241.

    PubMed  CAS  Google Scholar 

  122. Kunze, K. L., and Ortiz de Montellano, P. R., 1983, Formation of a sigma-bonded aryl-iron complex in the reaction of arylhydrazines with hemoglobin and myoglobin, J. Am. Chem. Soc. 105: 1380–1381.

    Article  CAS  Google Scholar 

  123. Ortiz de Montellano, P. R., and Kerr, D. E., 1983, Inactivation of catalase by phenylhydrazine: Formation of a stable aryl-iron heme complex, J. Biol. Chem. 258: 10558–10563.

    PubMed  CAS  Google Scholar 

  124. Ringe, D., Petsko, G. A., Kerr, D. E., and Ortiz de Montellano, P. R., 1984, Reaction of myoglobin with phenylhydrazine: A molecular doorstop, Biochemistry 23: 2–4.

    Article  PubMed  CAS  Google Scholar 

  125. Battioni, P., Mahy, J. -P., Delaforge, M., and Mansuy, D., 1983, Reaction of mono-substituted hydrazines and diazenes with rat-liver cytochrome P-450: Formation of ferrous-diazene and ferric sigma-alkyl complexes, Eur. J. Biochem. 134: 241–248.

    Article  PubMed  CAS  Google Scholar 

  126. Battioni, P., Mahy, J. -P., Gillet, G., and Mansuy, D., 1983, Iron porphyrin dependent oxidation of methyl-and phenylhydrazine: Isolation of iron(II)-diazene and sigmaalkyliron (III) (or aryliron(III)) complexes. Relevance to the reactions of hemoproteins with hydrazines, J. Am. Chem. Soc. 105: 1399–1401.

    Article  CAS  Google Scholar 

  127. Campbell, C. D., and Rees, C. W., 1969, Reactive intermediates. Part III. Oxidation of 1-aminobenzotriazole with oxidants other than lead tetra-acetate, J. Chem. Soc. C 1969: 752–756.

    Article  Google Scholar 

  128. Ortiz de Montellano, P. R., and Mathews, J. M., 1981, Autocatalytic alkylation of the cytochrome P-450 prosthetic haem group by 1-aminobenzotriazole: Isolation of an N,N-bridged benzyne—protoporphyrin IX adduct, Biochem. J. 195: 761–764.

    PubMed  CAS  Google Scholar 

  129. Ortiz de Montellano, P. R., Mathews, J. M., and Langry, K. C., 1984, Autocatalytic inactivation of cytochrome P-450 and chloroperoxidase by 1-aminobenzotriazole and other aryne precursors, Tetrahedron 40: 511–519.

    Article  CAS  Google Scholar 

  130. Costa, A. K., and Ortiz de Montellano, P. R., 1985, Dissociation of cytochrome P450 inactivation and induction, Fed. Proc. 44: 652.

    Google Scholar 

  131. Mathews, J. M., and Bend, J. R., 1985, Analogs of 1-aminobenzotriazole (ABT) as isozyme selective suicide inhibitors of rabbit pulmonary cytochrome P-450, Fed. Proc. 44: 1466.

    Google Scholar 

  132. Whitman, D. W., and Carpenter, B. K., 1980, Experimental evidence for nonsquare cyclobutadiene as a chemically significant intermediate in solution, J. Am. Chem. Soc. 102: 4272–4274.

    Article  CAS  Google Scholar 

  133. Stearns, R. A., and Ortiz de Montellano, P. R., 1985, Inactivation of cytochrome P450 by a catalytically generated cyclobutadiene species, J. Am. Chem. Soc. 107: 234240.

    Google Scholar 

  134. Stejskal, R., Itabashi, M., Stanek, J., and Hruban, Z., 1975, Experimental porphyria induced by 3-[2-(2,4,6-trimethylphenyl)-thioethyl]-4-methylsydnone, Virchows Arch. B 18: 83–100.

    CAS  Google Scholar 

  135. White, E. H., and Egger, N., 1984, Reaction of sydnones with ozone as a method of deamination: On the mechanism of inhibition of monoamine oxidase by sydnones, J. Am. Chem. Soc. 106: 3701–3703.

    Article  CAS  Google Scholar 

  136. Chevrier, B., Weiss, R., Lange, M. C., Chottard, J. -C., and Mansuy, D., 1981, An iron(III)—porphyrin complex with a vinylidene group inserted into an iron—nitrogen bond: Relevance of the structure of the active oxygen complex of catalase, J. Am. Chem. Soc. 103: 2899–2901.

    Article  CAS  Google Scholar 

  137. Latos-Grazynski, L., Cheng, R. -J., La Mar, G. N., and Balch, A. L., 1981, Reversible migration of an axial carbene ligand into an iron—nitrogen bond of a porphyrin: Implications for high oxidation states of heme enzymes and heme catabolism, J. Am. Chem. Soc. 103: 4271–4273.

    Article  Google Scholar 

  138. Grab, L. A., Ortiz de Montellano, P. R., Sutherland, E. P., and Marks, G. S., 1985, Mechanism-based inactivation of cytochrome P-450 by sydnones and inhibition of ferrochelatase by the resulting heme adduct, Fed. Proc. 44: 1610.

    Google Scholar 

  139. Schaefer, W. H., Harris, T. M., and Guengerich, F. P., 1985, Characterization of the enzymatic and non-enzymatic peroxidative degradation of iron porphyrins and cytochrome P-450 heme, Biochemistry 24: 3254–3263.

    Article  PubMed  CAS  Google Scholar 

  140. Nerland, D. E., Iba, M. M., and Mannering, G. J., 1981, Use of linoleic acid hydro-peroxide in the determination of absolute spectra of membrane-bound cytochrome P450, Mol. Pharmacol. 19: 162–167.

    PubMed  CAS  Google Scholar 

  141. Guzelian, P. S., and Swisher, R. W., 1979, Degradation of cytochrome P-450 haem by carbon tetrachloride and 2-allyl-2-isopropylacetamide in rat liver in vivo and in vitro: Involvement of non-carbon monoxide-forming mechanisms, Biochem. J. 184: 481–489.

    PubMed  CAS  Google Scholar 

  142. Ortiz de Montellano, P. R., and Kunze, K. L., 1980, Inactivation of hepatic cytochrome P-450 by allenic substrates, Biochem. Biophys. Res. Commun. 94: 443–449.

    Article  PubMed  CAS  Google Scholar 

  143. Hanzlik, R. P., Kishore, V., and Tullman, R., 1979, Cyclopropylamines as suicide substrates for cytochromes P-450, J. Med. Chem. 22: 759–761.

    Article  PubMed  CAS  Google Scholar 

  144. Macdonald, T. L., Zirvi, K., Burka, L. T., Peyman, P., and Guengerich, F. P., 1982, Mechanism of cytochrome P-450 inhibition by cyclopropylamines, J. Am. Chem. Soc. 104: 2050–2052.

    Article  CAS  Google Scholar 

  145. Ortiz de Montellano, P. R., and Mathews, J. M., 1981, Inactivation of hepatic cytochrome P-450 by a 1,2,3-benzothiadiazole insecticide synergist, Biochem. Pharmacol. 30: 1138–1141.

    Article  PubMed  CAS  Google Scholar 

  146. De Groot, H., and Haas, W., 1981, Self-catalyzed 02-independent inactivation of NADPH- or dithionite-reduced microsomal cytochrome P-450 by carbon tetrachloride, Biochem. Pharmacol. 30: 2343–2347.

    Article  PubMed  Google Scholar 

  147. Poli, G., Cheeseman, K., Slater, T. F., and Danzani, M. U., 1981, The role of lipid peroxidation in CC14-induced damage to liver microsomal enzymes: Comparative studies in vitro using microsomes and isolated liver cells, Chem. Biot Interact. 37: 13–24.

    Article  CAS  Google Scholar 

  148. Fernandez, G., Villaruel, M. C., de Toranzo, E. G. D., and Castro, J. A., 1982, Covalent binding of carbon to the heme moiety of cytochrome P-450 and its degradation products, Res. Commun. Chem. Pathol. Pharmacol. 35: 283–290.

    PubMed  CAS  Google Scholar 

  149. De Groot, H., Harnisch, U., and Noll, T., 1982, Suicidal inactivation of microsomal cytochrome P-450 by halothane under hypoxic conditions, Biochem. Biophys. Res. Commun. 107: 885–891.

    Article  PubMed  Google Scholar 

  150. Reiner, O., and Uehleke, H., 1971, Bindung von Tetrachlorkohlenstoff an reduziertes mikrosomales Cytochrome P-450 und an Ham, Hoppe-Seylers Z. Physiol. Chem. 352: 1048–1052.

    Article  PubMed  CAS  Google Scholar 

  151. Cox, P. J., King, L. J., and Parke, D. V., 1976, The binding of trichlorofluoromethane and other haloalkanes to cytochrome P-450 under aerobic and anaerobic conditions, Xenobiotica 6: 363–375.

    Article  PubMed  CAS  Google Scholar 

  152. Roland, W. C., Mansuy, D., Nastainczyk, W., Deutschmann, G., and Ullrich, V., 1977, The reduction of polyhalogenated methanes by liver microsomal cytochrome P450, Mol. Pharmac. 13: 698–705.

    Google Scholar 

  153. Mansuy, D., and Fontecave, M., 1983, Reduction of benzyl halides by liver microsomes: Formation of 478 nm-absorbing sigma-alkyl-ferric cytochrome P-450 complexes, Biochem. Pharmacol. 32: 1871–1879.

    Article  PubMed  CAS  Google Scholar 

  154. Mansuy, D., Lange, M., Chottard, J. C., Bartoli, J. F., Chevrier, B., and Weiss, R., 1978, Dichlorocarbene complexes of iron(II)-porphyrins—Crystal and molecular structure of FE(TPP)(CC12)(H2O), Angew. Chem. Int. Ed. Engl. 17: 781–782.

    Article  Google Scholar 

  155. Ahr, H. J., King, L. J., Nastainczyk, W., and Ullrich, V., 1980, The mechanism of chloroform and carbon monoxide formation from carbon tetrachloride by microsomal cytochrome P-450, Biochem. Pharmacol. 29: 2855–2861.

    Article  PubMed  CAS  Google Scholar 

  156. Mansuy, D., Lange, M., Chottard, J. C., and Bartoli, J. F., 1978, Reaction du complexe carbenique Fe(II)(tetraphenylporphyrine)(CC12) avec les amines primaires: Formation d’isonitriles, Tetrahedron Lett. 33: 3027–3030.

    Article  Google Scholar 

  157. Mansuy, D., and Battioni, J. -P., 1982, Isolation of sigma-alkyl-iron(III) or carbeneiron(II) complexes from reduction or polyhalogenated compounds by iron(II)-porphyrins: The particular case of halothane CF3CHC 1 Br, J. Chem. Soc. Chem. Commun. 1982: 638–639.

    Article  Google Scholar 

  158. Ruf, H. H., Ahr, H., Nastainczyk, W., Ullrich, V., Mansuy, D., Battioni, J.-P., Montiel-Montoya, R., and Trautwein, A., 1984, Formation of a ferric carbanion complex from halothane and cytochrome P-450: Electron spin resonance, electronic spectra and model complexes, Biochemistry 23: 5300–5306.

    Article  CAS  Google Scholar 

  159. Castro, C. E., Wade, R. S., and Belser, N. O., 1985, Biodehalogenation: Reactions of cytochrome P-450 with polyhalomethanes, Biochemistry 24: 204–210.

    Article  PubMed  CAS  Google Scholar 

  160. Callot, H. J., and Scheffer, E., 1980, Model for the in vitro transformation of cytochrome P-450 into “green pigments,” Tetrahedron Lett. 21: 1335–1338.

    Article  CAS  Google Scholar 

  161. Lange, M., and Mansuy, D., 1981, N-Substituted porphyrins formation from carbene iron-porphyrin complexes: A possible pathway for cytochrome P-450 heure destruction, Tetrahedron Lett. 22: 2561–2564.

    Article  CAS  Google Scholar 

  162. Chevrier, B., Weiss, R., Lange, M., Chotard, J. C., and Mansuy, D., 1981, An iron(III)—porphyrin complex with a vinylidene group inserted into an iron—nitrogen bond: Relevance to the structure of the active oxygen complex of catalase, J. Am. Chem. Soc. 103: 2899–2901.

    Article  CAS  Google Scholar 

  163. Olmstead, M. M., Cheng, R.-J., and Balch, A. L., 1982, X-Ray crystallographic characterization of an iron porphyrin with a vinylidene carbene inserted into an iron—nitrogen bond, Inorg. Chem. 21: 4143–4148.

    Article  CAS  Google Scholar 

  164. Guengerich, F. P., Dannan, G. A., Wright, T. S., Martin, M. V., and Kaminsky, L. S., 1982, Purification and characterization of liver microsomal cytochromes P-450: Electrophoretic, spectral, catalytic, and immunochemical properties and inducibility of eight isozymes isolated from rats treated with phenobarbital or beta-naphthoflavone, Biochemistry 21: 6019–6030.

    Article  PubMed  CAS  Google Scholar 

  165. Ortiz de Montellano, P. R., Mico, B. A., Mathews, J. M., Kunze, K. L., Miwa, G. T., and Lu, A. Y. H., 1981, Selective inactivation of cytochrome P-450 isozymes by suicide substrates, Arch. Biochem. Biophys. 210: 717–728.

    Article  PubMed  CAS  Google Scholar 

  166. Kellis, J. T., Sheets, J. J., and Vickery, L. E., 1984, Amino-steroids as inhibitors and probes of the active site of cytochrome P-450scc. Effects on the enzyme from different sources, J. Steroid Biochem. 20: 671–676.

    Article  PubMed  CAS  Google Scholar 

  167. Sheets, J. J., and Vickery, L. E., 1983, Active site-directed inhibitors of cytochrome P-450,cc: Structural and mechanistic implication of a side chain-substituted series of amino-steroids, J. Biol. Chem. 258: 11446–11452.

    PubMed  CAS  Google Scholar 

  168. Sheets, J. J., and Vickery, L. E., 1982, Proximity of the substrate binding site and the heure-iron catalytic site in cytochrome P-450,cc, Proc. Natl. Acad. Sci. USA 79: 5773–5777.

    Article  PubMed  CAS  Google Scholar 

  169. Nagahisa, A., Foo, T., Gut, M., and Orme-Johnson, W. H., 1985, Competitive inhibition of cytochrome P-450, by (22R)- and (22S)-22-aminocholesterol: Side chain stereochemical requirements for C-22 amine coordination to the active-site heure, J. Biol. Chem. 260: 846–851.

    PubMed  CAS  Google Scholar 

  170. Nagahisa, A., Spencer, R. W., and Orme-Johnson, W. H., 1983, Acetylenic mechanism-based inhibitors of cholesterol side chain cleavage by cytochrome P-450,cc, J. Biol. Chem. 258: 6721–6723.

    PubMed  CAS  Google Scholar 

  171. Nagahisa, A., Orme-Johnson, W. H., and Wilson, S. R., 1984, Silicon mediated suicide inhibition: An efficient mechanism-based inhibitor of cytochrome P-450sce oxidation of cholesterol, J. Am. Chem. Soc. 106: 1166–1167.

    Article  CAS  Google Scholar 

  172. Trahanovsky, W. S., and Himstedt, A. L., 1974, Oxidation of organic compounds with cerium(IV). XX. Abnormally rapid rate of oxidative cleavage of (beta-trimethylsilylethyl)phenylmethanol, J. Am. Chem. Soc. 96: 7974–7976.

    Article  CAS  Google Scholar 

  173. Brodie, A. M. H., Marsh, D., and Brodie, H. J., 1979, Aromatase inhibitors. IV. Regression of hormone-dependent, mammary tumors in the rat with 4-acetoxy-4-androstene-3,17-dione, J. Steroid Biochem. 10: 423–429.

    Article  PubMed  CAS  Google Scholar 

  174. Henderson, I. C., and Canellos, G. P., 1980, Cancer of the breast (The past decade), N. Engl. J. Med. 302: 78–90.

    Article  PubMed  CAS  Google Scholar 

  175. Santen, R. J., Worgul, T. J., Samojlik, E., Interrante, A., Boucher, A. E., Lipton, A., Harvey, H. A., White, D. S., Smart, E., Cox, C., and Wells, S. A., 1981, A randomized trial comparing surgical adrenalectomy with aminoglutethimide plus hydrocortisone in women with advanced breast cancer, N. Engl. J. Med. 305: 545–551.

    Article  PubMed  CAS  Google Scholar 

  176. Phillips, G. B., Castelli, W. P., Abbott, R. D., and McNamara, P. M., 1983, Association of hyperestrogenemia and coronary heart disease in men in the Framingham cohort, Am. J. Med. 74: 863–869.

    Article  PubMed  CAS  Google Scholar 

  177. Harris, A. L., Powles, T. J., Smith, I. E., Coombes, R. C., Ford, H. T., Gazet, J. C., Harmer, C. L., Morgan, M., White, H., Parsons, C. A., and McKinna, J. A., 1983, Aminoglutethimide for the treatment of advanced postmenopausal breast cancer, Eur. J. Cancer Clin. Oncol. 19: 11–17.

    Article  PubMed  CAS  Google Scholar 

  178. Metcalf, B. W., Wright, C. L., Burkhart, J. P., and Johnston, J. O., 1981, Substrate-induced inactivation of aromatase by allenic and acetylenic steroids, J. Am. Chem. Soc. 103: 3221–3222.

    Article  CAS  Google Scholar 

  179. Covey, D. G., Hood, W. F., and Parikh, V. D., 1981, 10-Beta-propynyl-substituted steroids, J. Biol. Chem. 256: 1076–1079.

    Google Scholar 

  180. Marcotte, P. A., and Robinson, C. H., 1982, Synthesis and evaluation of 10-betasubstituted 4-estrene-3,17-diones as inhibitors of human placental microsomal aromatase, Steroids 39: 325–344.

    Article  PubMed  CAS  Google Scholar 

  181. Marcotte, P. A., and Robinson, C. H., 1982, Design of mechanism-based inactivators of human placental aromatase, Cancer Res. 42: 3322–3325.

    CAS  Google Scholar 

  182. Flynn, G. A., Johnston, J. O., Wright, C. L., and Metcalf, B. W., 1981, The time-dependent inactivation of aromatase by 17-beta-hydroxy-l0-methylthioestra-1,4-dien3-one, Biochem. Biophys. Res. Acta 103: 913–918.

    Article  CAS  Google Scholar 

  183. Covey, D. F., and Hood, W. F., 1982, Aromatase enzyme catalysis is involved in the potent inhibition of estrogen biosynthesis caused by 4-acetoxy-and 4-hydroxy-4-androstene-3,17-dione, Mol. Pharmacol. 21: 173–180.

    PubMed  CAS  Google Scholar 

  184. Brodie, A. M. H., Garrett, W. M., Hendrickson, J. R., Tsai-Morris, C.-H., Marcotte, P. A., and Robinson, C. H., 1981, Inactivation of aromatase in vitro by 4-hydroxy-4androstene-3,17-dione and 4-acetoxy-4-androstene-3,17-dione and sustained effects in vivo, Steroids 38: 693–702.

    Article  PubMed  CAS  Google Scholar 

  185. Covey, D. E., Hood, W. F., Bensen, D. D., and Carrell, H. L., 1984, Hydroperoxides as inactivators of aromatase: 10-Beta-hydroperoxy-4-estrene-3,17-dione, crystal structure and inactivation characteristics, Biochemistry 23: 5398–5406.

    Article  PubMed  CAS  Google Scholar 

  186. Vanden Bossche, H., Willemsens, G., Cools, W., Marichal, P., and Lauwers, W., 1983, Hypothesis on the molecular basis of the antifungal activity of N-substituted imidazoles and triazoles, Biochem. Soc. Trans. 11: 665–667.

    CAS  Google Scholar 

  187. Vanden Bossche, H., Lauwers, W., Willemsens, G., Marichal, P., Cornelissen, F., and Cools, W., 1984, Molecular basis for the antimycotic and antibacterial activity of N-substituted imidazoles and triazoles: The inhibition of isoprenoid biosynthesis, Pes-tic. Sci. 15: 188–198.

    Article  Google Scholar 

  188. Heeres, J., De Brabander, M., and Vanden Bossche, H., 1982, Ketoconazole: Chemistry and basis for selectivity, in: Current Chemotherapy and Immunotherapy, Volume 2 ( P. Periti and G. G. Grossi, eds.), American Society of Microbiology, Washington, D.C., pp. 1007–1009.

    Google Scholar 

  189. Willemsens, G., Cools, W., and Vanden Bossche, H., 1980, Effects of miconazole and ketoconazole on sterol synthesis in a subcellular fraction of yeast and mammalian cells, in: The Host Invader Interplay ( H. Van den Bossche, ed.), Elsevier/North Holland, Amsterdam, pp. 691–694.

    Google Scholar 

  190. Murray, M., Ryan, A. J., and Little, P. J., 1982, Inhibition of rat hepatic microsomal aminopyrine N-demethylase activity by benzimidazole derivatives: Quantitative structure–activity relationships, J. Med. Chem. 25: 887–892.

    Article  PubMed  CAS  Google Scholar 

  191. Santen, R. J., Vanden Bossche, H., Symoens, J., Brugmans, J., and DeCoster, R., 1983, Site of action of low dose ketoconazole or androgen biosynthesis in men, J. Clin. Endocrinol. Metab. 57: 732–736.

    Article  PubMed  CAS  Google Scholar 

  192. Gander, P., Mercer, E. I., Baldwin, B. C., and Wiggins, T. E., 1983, A comparison of the potency of some fungicides as inhibitors of sterol 14-demethylation, Pestic. Biochem. Physiol. 19: 1–10.

    Google Scholar 

  193. Nes, W. R., 1974, Role of sterols in membranes, Lipids 9: 596–612.

    Article  PubMed  CAS  Google Scholar 

  194. Yeagle, P. L., Martin, R. B., Lala, A. K., Lin, H.-K., and Block, K., 1977, Differential effects of cholesterol and lanosterol on artificial membranes, Proc. Natl. Acad. Sci. USA 74: 4924–4926.

    Article  PubMed  CAS  Google Scholar 

  195. Freter, C. E., Laderson, R. C., and Sibert, D. F., 1979, Membrane phospholipid alterations in response to sterol depletion of LM cells, J. Biol. Chem. 254: 6909–6916.

    PubMed  CAS  Google Scholar 

  196. Shak, S., and Goldstein, I., 1984, Omega-oxidation is the major pathway for the catabolism of leukotriene B4 in human polymorphonuclear leukocytes, J. Biol. Chem. 259: 10181–10187.

    PubMed  CAS  Google Scholar 

  197. Kupfer, D., 1982, Endogenous substrates of monooxygenases: Fatty acids and Prostaglandins, in: Hepatic Cytochrome P-450 Monooxygenase System ( J. B. Schenkman and D. Kupfer, eds.), Pergamon Press, Elmsford, N.Y., pp. 157–190.

    Google Scholar 

  198. Matson, R. S., Stein, R. A., and Fulco, A. J., 1980, Hydroxylation of 9-hydroxystearate by a soluble cytochrome P-450-dependent fatty acid hydroxylase from Bacillus megaterium, Biochem. Biophys. Res. Commun. 97: 955–961.

    Article  PubMed  CAS  Google Scholar 

  199. Kupfer, D., 1980, Endogenous substrates of monooxygenases: Fatty acids and Prostaglandins, Pharmacol. Ther. A 11: 469–496.

    Article  CAS  Google Scholar 

  200. Ortiz de Montellano, P. R., and Reich, N. O., 1984, Specific inactivation of hepatic fatty acid hydroxylases by acetylenic fatty acids, J. Biol. Chem. 259: 4136–4141.

    PubMed  CAS  Google Scholar 

  201. Salaun, J. P., Reichhart, D., Simon, A., Durst, F., Reich, N. O., and Ortiz de Montellano, P. R., 1984, Autocatalytic inactivation of plant cytochrome P-450 enzymes: Selective inactivation of the lauric acid in-chain hydroxylase from Helianthas tuberosus L. by unsaturated substrate analogs, Arch. Biochem. Biophys. 232: 1–7.

    Article  PubMed  CAS  Google Scholar 

  202. CaJacob, C. A., and Ortiz de Montellano, P. R., 1985, Sodium 10-undecynyl sulfate: A specific in vivo irreversible inhibitor of fatty acid hydroxylases, Fed. Proc. 44: 1611.

    Google Scholar 

  203. Clancy, R. M., Dahinden, C. A., and Hugli, T. E., 1984, Oxidation of leukotrienes at the u end: Demonstration of a receptor for the 20-hydroxy derivative of leukotriene B4 on human neutrophils and implications for the analysis of leukotriene receptors, Proc. Natl. Acad. Sci. USA 81: 5729–5733.

    Article  PubMed  CAS  Google Scholar 

  204. Shak, S., Reich, N. O., Goldstein, I. M., and Ortiz de Montellano, P. R., 1985, Leukotriene B4 w-hydroxylase in human polymorphonuclear leukocytes: Suicidal inactivation by acetylenic fatty acids, J. Biol. Chem. 260: 13023–13028.

    PubMed  CAS  Google Scholar 

  205. Masters, B. S. S., Okita, R. T., Ortiz de Montellano, P. R., Reich, N. O., and Williams, D. E., 1985, Pulmonary cytochrome P-450-mediated fatty acid and prostaglandin (PG) hydroxylation—Inhibition by antibodies and suicide substrates, Fed. Proc. 44: 651.

    Google Scholar 

  206. Feyereisen, R., Farnsworth, D. E., Prickett, K. S., and Ortiz de Montellano, P. R., 1985, Suicidal destruction of cytochrome P-450 in the design of inhibitors of insect juvenile hormone biosynthesis, in: Bioregulators for Pest Control. American Chemical Society Symposium Series No. 276, American Chemical Society, Washington, D.C., pp. 255–266.

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Authors and Affiliations

  1. Department of Pharmaceutical Chemistry, School of Pharmacy, University of California, San Francisco, California, 94143, USA

    Paul R. Ortiz de Montellano & Norbert O. Reich

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  1. Paul R. Ortiz de Montellano
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  2. Norbert O. Reich
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Editors and Affiliations

  1. Department of Pharmaceutical Chemistry, School of Pharmacy, University of California, San Francisco, 94143, San Francisco, California, USA

    Paul R. Ortiz de Montellano

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© 1986 Springer Science+Business Media New York

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de Montellano, P.R.O., Reich, N.O. (1986). Inhibition of Cytochrome P-450 Enzymes. In: de Montellano, P.R.O. (eds) Cytochrome P-450. Springer, Boston, MA. https://doi.org/10.1007/978-1-4757-9939-2_8

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  • DOI: https://doi.org/10.1007/978-1-4757-9939-2_8

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