Inhibition of Drug Metabolizing Enzymes

Handbook of Drug Metabolism, Second Edition

Volumn , Issue , 2008, Pages 203-226

  Guengerich, F Peter ^a  

^a VANDERBILT UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

EID: 85137874192     PISSN: None     EISSN: None     Source Type: Book    
DOI: 10.3109/9781420076486-11     Document Type: Chapter

References (152)

1. Guengerich FP. Role of cytochrome P450 in drug interactions. Adv Pharmacol 1997; 43:7-35.
2. Guengerich FP. Inhibition of drug metabolizing enzymes: molecular and biochemical aspects. In: Woolf TF, ed. Handbook of Drug Metabolism. New York: Marcel Dekker, 1999:203-227.
3. Segel IH. Enzyme Kinetics. New York: Wiley, 1975.
4. Cornish-Bowden A. Analysis of Enzyme Kinetics. Oxford: Oxford Univ Press, 1995.
5. Silverman RB. Mechanism-based Enzyme Inactivation: Chemistry and Enzymology. Boca Raton, FL: CRC Press, 1988.
6. Kuby SA. A Study of Enzymes, Vol. I, Enzyme Catalysis, Kinetics, and Substrate Binding. Boca Raton, FL: CRC Press, 1991.
7. Bronson DD, Daniels DM, Dixon JT, Redick CC, Haaland PD. Virtual kinetics: using statistical experimental design for rapid analysis of enzyme inhibitor mechanisms. Biochem Pharmacol 1995; 50:823-831.
8. Renwick AG. Toxicokinetics. In: Hayes AW, ed. Principles and Methods of Toxicology. 5th ed. New York: Raven Press, 2007:179-230.
9. von Moltke LL, Greenblatt DJ, Duan SX, et al. In vitro prediction of the terfenadineketoconazole pharmacokinetic interaction. J Clin Pharmacol 1994; 34:1222-1227.
10. Black DJ, Kunze KL, Wienkers LC, Gidal BE, Seaton TL, Mcdonnell ND, Evans JS, Bauwens JE, Trager WF. Warfarin-fluconazole II. A metabolically based drug interaction: in vivo studies. Drug Metab Dispos 1996; 24:422-428.
11. Vermilion JL, Coon MJ. Purified liver microsomal NADPH-cytochrome P-450 reductase:spectral characterization of oxidation-reduction states. J Biol Chem 1978; 253:2694-2704.
12. Guengerich FP, Bartleson CJ. Analysis and characterization of enzymes and nucleic acids. In:Hayes AW, ed. Principles and Methods of Toxicology. 5th ed. Boca Raton, FL: CRC Press, 2007:1981-2048.
13. Guengerich FP, Kim D-H, Iwasaki M. Role of human cytochrome P-450 IIE1 in the oxidation of many low molecular weight cancer suspects. Chem Res Toxicol 1991; 4:168-179.
14. Shimada T, Guengerich FP. Inhibition of human cytochrome P450 1A1, 1A2, and 1B1- mediated activation of procarcinogens to genotoxic metabolites by polycyclic aromatic hydrocarbons. Chem Res Toxicol 2006; 19:288-294.
15. Shimada T, Murayama N, Okada K, Funae Y, Yamazaki H, Guengerich FP. Different mechanisms for inhibition of human cytochromes P450 1A1, 1A2 and 1B1 by polycyclic aromatic inhibitors. Chem Res Toxicol 2007; 20:489-496.
16. Haldane JBS. Enzymes. London: Longmans, Green, 1930.
17. Pauling L. Chemical achievement and hope for the future. Am Sci 1948; 36:51-58.
18. Lerner RA, Benkovic SJ. Principles of antibody catalysis. BioEssays 1988; 9:107-112.
19. Silverman RB. Mechanism-based enzyme inactivators. Methods Enzymol 1995; 249:240-283.
20. Tian GC, Mook RA, Moss ML, Frye SV. Mechanism of time-dependent inhibition of 5 alphareductases by delta(1)-4-azasteroids: Toward perfection of rates of time-dependent inhibition by using ligand-binding energies. Biochemistry 1995; 34:13453-13459.
21. Marnett LJ. Cyclooxygenase mechanisms. Curr Opin Chem Biol 2000; 4:545-552.
22. Abeles RH, Maycock AL. Suicide enzyme inactivators. Acc Chem Res 1976; 9:313-319.
23. Rando RR. Mechanism-based enzyme inactivators. Pharmacol Rev 1984; 36:111-142.
24. Walsh CT. Suicide substrates, mechanism-based enzyme inactivators: recent developments. Annu Rev Biochem 1984; 53:493-535.
25. Abeles RH and Alston TA. Enzyme inhibition by fluoro compounds. J Biol Chem 1990; 265:16705-16708.
26. Waley SG. Kinetics of suicide substrates. Biochem J 1980; 185:771-773.
27. Waley SG. Kinetics of suicide substrates: practical procedures for determining parameters. Biochem J 1985; 227:843-849.
28. Halpert JR, Guengerich FP. Enzyme inhibition and stimulation. In: Guengerich FP, ed. Biotransformation, Vol. 3, Comprehensive Toxicology. 1st ed. Oxford: Elsevier, 1997:21-35.
29. Correia MA. Human and rat liver cytochromes P450: functional markers, diagnostic inhibitor probes, and parameters frequently used in P450 studies. In: Ortiz de Montellano PR, ed. Cytochrome P450: Structure, Mechanism, and Biochemistry. 3rd ed. New York: Plenum Press, 2005:619-657.
30. Xiao X, Prestwich GD. 29-Methylidene-2, 3-oxidosqualene: a potent mechanism-based inactivator of oxidosqualene cyclase. J Am Chem Soc 1991; 113:9673-9674.
31. Schechter PJ, Sjoerdsma A. Therapeutic utility of selected enzyme-activated irreversible inhibitors. In: Enzymes as Targets for Drug Design. New York: Academic Press, 1990:201-210.
32. Bach AWJ, Lan NC, Johnson DL, et al. cDNA cloning of human liver monoamine oxidase A and B: molecular basis of differences in enzymatic properties. Proc Natl Acad Sci U S A 1988; 85:4934-4938.
33. Dostert PL, Benedetti MS, Tipton KF. Interactions of monoamine oxidase with substrates and inhibitors. Med Res Rev 1989; 9:45-89.
34. Silverman RB. Mechanism of inactivation of monoamine oxidase by trans-2-phenylcyclopropylamine and the structure of the enzyme-inactivator adduct. J Biol Chem 1983; 258:14766-14769.
35. Silverman RB, Ding CZ. Chemical model for a mechanism of inactivation of monoamine oxidase by heterocylic compounds. Electronic effects on acetal hydrolysis. J Am Chem Soc 1993; 115:4571-4576.
36. Mitchell DJ, Nikolic D, Rivera E, Sablin SO, Choi S, van Breemen RB, Singer TP, Silverman RB. Spectrophotometric evidence for the flavin-1-phenylcyclopropylamine inactivator adduct with monoamine oxidase N. Biochemistry 2001; 40:5447-5456.
37. Mitchell DJ, Nikolic D, van Breemen RB, Silverman RB. Inactivation of monoamine oxidase B by 1-phenylcyclopropylamine: Mass spectral evidence for the flavin adduct. Bioorg Med Chem Lett 2001; 11:1757-1760.
38. Tipton KF, McCrodden JM, Youdim MBH. Oxidation and enzyme-activated irreversible inhibition of rat liver monoamine oxidase-B by 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP). Biochem J 1986; 240:379-383.
39. Rimoldi JM, Wang YX, Nimkar SK, Kuttab SH, Anderson AH, Burch H, Castagnoli N Jr. Probing the mechanism of bioactivation of MPTP type analogs by monoamine oxidase B:structure-activity studies on substituted 4-phenoxy-, 4-phenyl-, and 4-thiophenoxy-1-cyclopropyl-1, 2, 3, 6-tetrahydropyridines. Chem Res Toxicol 1995; 8:703-710.
40. Newton DJ, Wang RW, Lu AYH. Cytochrome P450 inhibitors: evaluation of specificities in the in vitro metabolism of therapeutic agents by human liver microsomes. Drug Metab Dispos 1994; 23:154-158.
41. Bourrié M, Meunier V, Berger Y, Fabre G. Cytochrome P450 isoform inhibitors as a tool for the investigation of metabolic reactions catalyzed by human liver microsomes. J Pharmacol Exp Ther 1996; 277:321-332.
42. Chang TKH, Gonzalez FJ, Waxman DJ. Evaluation of triacetyloleandomycin, a-naphthoflavone and diethyldithiocarbamate as selective chemical probes for inhibition of human cytochrome P450. Arch Biochem Biophys 1994; 311:437-442.
43. Denton TT, Zhang X, Cashman JR. 5-substituted, 6-substituted, and unsubstituted 3-heteroaromatic pyridine analogues of nicotine as selective inhibitors of cytochrome P-450 2A6. J Med Chem 2005; 48:224-239.
44. Mancy A, Dijols S, Poli S, Guengerich FP, Mansuy D. Interaction of sulfaphenazole derivatives with human liver cytochromes P450 2C: molecular origin of the specific inhibitory effects of sulfaphenazole on CYP 2C9 and consequences for the substrate binding topology. Biochemistry 1997; 35:16205-16212.
45. Strobl GR, von Kruedener S, Stöckigt J, Guengerich FP, Wolff T. Development of a pharmacophore for inhibition of human liver cytochrome P-450 2D6: molecular modeling and inhibition studies. J Med Chem 1993; 36:1136-1145.
46. Guengerich FP, Müller-Enoch D, Blair IA. Oxidation of quinidine by human liver cytochrome P-450. Mol Pharmacol 1986; 30:287-295.
47. Halpert JR. Structural basis of selective cytochrome P450 inhibition. Annu Rev Pharmacol Toxicol 1995; 35:29-53.
48. Vanden Bossche H, Koymans L, Moereels H. P450 inhibitors of use in medical treatment:focus on mechanisms of action. Pharmacol Ther 1995; 67:79-100.
49. Guengerich FP. Human cytochrome P450 enzymes. In: Ortiz de Montellano PR, ed. Cytochrome P450: Structure, Mechanism, and Biochemistry. 3rd ed. New York: Plenum Press, 2005:377-530.
50. Brodie AMH. Aromatase, its inhibitors and their use in breast cancer treatment. Pharmacol Ther 1993; 60:501-515.
51. Aoyama Y, Yoshida Y, Nishino T, Katsuki H, Maitra US, Mohan VP, Sprinson DB. Isolation and characterization of an altered cytochrome P-450 from a yeast mutant defective in lanosterol 14a-demethylation. J Biol Chem 1987; 262:14260-14264.
52. Vanden Bossche H. Inhibitors of P450-dependent steroid biosynthesis: from research to medical treatment. J Steroid Biochem Mol Biol 1992; 43:1003-1021.
53. Sonino N. The use of ketoconazole as an inhibitor of steroid production. New Engl J Med 1987; 317:812-818.
54. Baldwin SJ, Bloomer JC, Smith GJ, Ayrton AD, Clarke SE, Chenery RJ. Ketoconazole and sulphaphenazole as the respective selective inhibitors of P4503A and 2C9. Xenobiotica 1995; 25:261-270.
55. Casida JE. Mixed function oxidase involvement in the biochemistry of insecticide synergists. J Agric Food Chem 1970; 18:753-772.
56. Hammons GJ, Alworth WL, Hopkins NE, Guengerich FP, Kadlubar FF. 2-Ethynylnaphthalene as a mechanism-based inactivator of the cytochrome P-450 catalyzed N-oxidation of 2- naphthylamine. Chem Res Toxicol 1989; 2:367-374.
57. Viaje A, Lu JYL, Hopkins NE, Nettikumara AN, DiGiovanni J, Alworth WL, Slaga TJ. Inhibition of the binding of 7, 12-dimethylbenz[a]anthracene and benzo[a]pyrene to DNA in mouse skin epidermis by 1-ethynylpyrene. Carcinogenesis 1990; 11:1139-1143.
58. Davidson NE, Egner PA, Kensler TW. Transcriptional control of glutathione S-transferase gene expression by the chemoprotective agent 5-(2-pyrazinyl)-4-methyl-1, 2-dithiole-3-thione (oltipraz) in rat liver. Cancer Res 1990; 50:2251-2255.
59. Zhang Y, Talalay P, Cho CG, Posner GH. A major inducer of anticarcinogenic protective enzyme from broccoli: isolation and elucidation of structure. Proc Natl Acad Sci U S A 1992; 89:2399-2403.
60. Langouët S, Coles B, Morel F, Becquemont L, Beaune PH, Guengerich FP, Ketterer B, Guillouzo A. Inhibition of CYP1A2 and CYP3A4 by oltipraz results in reduction of aflatoxin B1 metabolism in human hepatocytes in primary culture. Cancer Res 1995; 55:5574-5579.
61. Koymans L, Vermeulen NPE, van Acker SABE, te Koppele JM, Heykants JJP, Lavrijsen K, Meuldermans W, Donné-Op den Kelder GM. A predictive model for substrates of cytochrome P450-debrisoquine (2D6). Chem Res Toxicol 1992; 5:211-219.
62. Wolff T, Distlerath LM, Worthington MT, Groopman JD, Hammons GJ, Kadlubar FF, Prough RA, Martin MV, sGuengerich FP. Substrate specificity of human liver cytochrome P-450 debrisoquine 4-hydroxylase probed using immunochemical inhibition and chemical modeling. Cancer Res 1985; 45:2116-2122.
63. Guengerich FP, Miller GP, Hanna IH, Martin MV, Léger S, Black C, Chauret N, Silva JM, Trimble L, Jergey JA, Nicoll-Griffith DA. Diversity in the oxidation of substrates by cytochrome P450 2D. Lack of an obligatory role of aspartate 301-substrate electrostatic bonding. Biochemistry 2002; 41:11025-11034.
64. Murray M and Wilkinson CF. Interactions of nitrogen heterocycles with cytochrome P-450 and monooxygenase activity. Chem Biol Interact 1984; 50:267-275.
65. Brian WR, Srivastava PK, Umbenhauer DR, Lloyd RS, Guengerich FP. Expression of a human liver cytochrome P-450 protein with tolbutamide hydroxylase activity in Saccharomyces cerevisiae. Biochemistry 1989; 28:4993-4999.
66. Miners JO, Smith KJ, Robson RA, McManus ME, Veronese ME, Birkett DJ. Tolbutamide hydroxylation by human liver microsomes: kinetic characterisation and relationship to other cytochrome P-450 dependent xenobiotic oxidations. Biochem Pharmacol 1988; 37:1137-1144.
67. Yoo JSH, Cheung RJ, Patten CJ, Wade D, Yang CS. Nature of N-nitrosodimethylamine demethylase and its inhibitors. Cancer Res 1987; 47:3378-3383.
68. Chauret N, Gauthier A, Nicoll-Griffith DA. Effect of common organic solvents on in vitro cytochrome P450-mediated metabolic activities in human liver microsomes. Drug Metab Dispos 1998; 26:1-4.
69. Danan G, Descatoire V, Pessayre D. Self-induction by erythromycin of its own transformation into a metabolite forming an inactive complex with reduced cytochrome P-450. J Pharmacol Exp Ther 1981; 218:509-514.
70. Jönsson KH, Lindeke B. Cytochrome P-455 nm complex formation in the metabolism of phenylalkylamines. XII. Enantioselectivity and temperature dependence in microsomes and reconstituted cytochrome P-450 systems from rat liver. Chirality 1992; 4:469-477.
71. Murray M, Wilkinson CF, Marcus C, Dubé CE. Structure-activity relationships in the interactions of alkoxymethylenedioxybenzene derivatives with rat hepatic microsomal mixedfunction oxidases in vivo. Mol Pharmacol 1983; 24:129-136.
72. Ortiz de Montellano PR, Correia MA. Suicidal destruction of cytochrome P-450 during oxidative drug metabolism. Annu Rev Pharmacol Toxicol 1983; 23:481-503.
73. Ortiz de Montellano PR, Reich NO. Inhibition of cytochrome P-450 enzymes. In: Ortiz de Montellano PR, ed. Cytochrome P-450: Structure, Mechanism, and Biochemistry, 1st ed., New York: Plenum Press, 1986:273-314.
74. Halpert JR, Balfour C, Miller NE, Kaminsky LS. Dichloromethyl compounds as mechanismbased inactivators of rat liver cytochromes P-450 in vitro. Mol Pharmacol 1986; 30:19-24.
75. Miller NE, Halpert J. Analogues of chloramphenicol as mechanism-based inactivators of rat liver cytochrome P-450: modifications of the propanediol side chain, the p-nitro group, and the dichloromethyl moiety. Mol Pharmacol 1986; 29:391-398.
76. Macdonald TL, Zirvi K, Burka LT, Peyman P, Guengerich FP. Mechanism of cytochrome P-450 inhibition by cyclopropylamines. J Am Chem Soc 1982; 104:2050-2052.
77. Hanzlik RP, Tullman RH. Suicidal inactivation of cytochrome P-450 by cyclopropylamines. Evidence for cation-radical intermediates. J Am Chem Soc 1982; 104:2048-2050.
78. Bondon A, Macdonald TL, Harris TM, Guengerich FP. Oxidation of cycloalkylamines by cytochrome P-450. Mechanism-based inactivation, adduct formation, ring expansion, and nitrone formation. J Biol Chem 1989; 264:1988-1997.
79. Augusto O, Beilan HS, Ortiz de Montellano PR. The catalytic mechanism of cytochrome P-450: spin-trapping evidence for one-electron substrate oxidation. J Biol Chem 1982; 257:11288-11295.
80. Ortiz de Montellano PR, Beilan HS, Kunze KL. N-Alkylprotoporphyrin IX formation in 3, 5-dicarbethoxy-1, 4-dihydrocollidine-treated rats: transfer of the alkyl group from the substrate to the porphyrin. J Biol Chem 1981; 256:6708-6713.
81. Böcker RH, Guengerich FP. Oxidation of 4-aryl- and 4-alkyl-substituted 2, 6-dimethyl-3, 5-bis (alkoxycarbonyl)-1, 4-dihydropyridines by human liver microsomes and immunochemical evidence for the involvement of a form of cytochrome P-450. J Med Chem 1986; 29:1596-1603.
82. Lukton D, Mackie JE, Lee JS, Marks GS, Ortiz de Montellano PR. 2, 2-Dialkyl-1, 2-dihydroquinolines: cytochrome P-450 catalyzed N-alkylporphyrin formation, ferrochelatase inhibition, and induction of 5-aminolevulinic acid synthase activity. Chem Res Toxicol 1988; 1:208-215.
83. Stearns RA, Ortiz de Montellano PR. Inactivation of cytochrome P-450 by a catalytically generated cyclobutadiene species. J Am Chem Soc 1985; 107:234-240.
84. Meschter CL, Mico BA, Mortillo M, Feldman D, Garland WA, Riley JA, Kaufman LS. A 13-week toxicologic and pathologic evaluation of prolonged cytochromes P450 inhibition by 1-aminobenzotriazole in male rats. Fundam Appl Toxicol 1994; 22:369-381.
85. Correia MA, Ortiz de Montellano PR. Inhibition of cytochrome P450 enzymes. In: Ortiz de Montellano PR, ed. Cytochrome P450: Structure, Mechanism, and Biochemistry. 3rd ed. New York: Kluwer Academic/Plenum Publishers, 2005:247-322.
86. Sahali-Sahly Y, Balani SK, Lin JH, Baillie TA. In vitro studies on the metabolic activation of the furanopyridine L-754, 394, a highly potent and selective mechanism-base inhibitor of cytochrome P450 3A4. Chem Res Toxicol 1996; 9:1007-1012.
87. Kassahun K, Skordos K, McIntosh I, Slaughter D, Doss GA, Baillie TA, Yost GS. Zafirlukast metabolism by cytochrome P450 3A4 produces an electrophilic alpha, beta-unsaturated iminium species that results in the selective mechanism-based inactivation of the enzyme. Chem Res Toxicol 2005; 18:1427-1437.
88. Chen Q, Ngui JS, Doss GA, Wang RW, Cai X, DiNinno FP, Blizzard TA, Hammond ML, Stearns RA, Evans DC, Baillie TA, Tang W. Cytochrome P450 3A4-mediated bioactivation of raloxifene: irreversible enzyme inhibition and thiol adduct formation. Chem Res Toxicol 2002; 15:907-914.
89. Crowley JR, Hollenberg PF. Mechanism-based inactivation of rat liver cytochrome P4502B1 by phencyclidine and its oxidative product, the iminium ion. Drug Metab Dispos 1995; 23:786-793.
90. Roberts ES, Hopkins NE, Zaluzec EJ, Gage DA, Alworth WL, Hollenberg PF. Mechanismbased inactivation of cytochrome P450 2B1 by 9-ethynylphenanthrene. Arch Biochem Biophys 1995; 323:295-302.
91. Roberts ES, Ballou DP, Hopkins NE, Alworth WL, Hollenberg PF. Mechanistic studies of 9-ethynylphenanthrene-inactivated cytochrome P450 2B1. Arch Bioche Biophys 1995; 323:303-312.
92. Sharma U, Roberts ES, Hollenberg PF. Inactivation of cytochrome P4502B1 by the monoamine oxidase inhibitors R-(-)-deprenyl and clorgyline. Drug Metab Dispos 1996; 24:669-675.
93. Sharma U, Roberts ES, Hollenberg PF. Formation of a metabolic intermediate complex of cytochrome P4502B1 by clorgyline. Drug Metab Dispos 1996; 24:1247-1253.
94. Kent UM, Roberts ES, Chun J, Hodge K, Juncaj J, Hollenberg PF. Inactivation of cytochrome P450 2E1 by tert-butylisothiocyanate. Chem Res Toxicol 1998; 11:1154-1161.
95. Yanev S, Kent UM, Pandova B, Hollenberg PF. Selective mechanism-based inactivation of cytochromes P-450 2B1 and P-450 2B4 by a series of xanthates. Drug Metab Dispos 1999; 27:600-604.
96. Kent UM, Yanev S, Hollenberg PF. Mechanism-based inactivation of cytochromes P450 2B1 and P450 2B6 by n-propylxanthate. Chem Res Toxicol 1999; 12:317-322.
97. Regal KA, Schrag ML, Kent UM, Wienkers LC, Hollenberg PF. Mechanism-based inactivation of cytochrome P450 2B1 by 7-ethynylcoumarin: verification of apo-P450 adduction by electrospray ion trap mass spectrometry. Chem Res Toxicol 2000; 13:262-270.
98. Jushchyshyn MI, Kent UM, Hollenberg PF. The mechanism-based inactivation of human cytochrome P450 2B6 by phencyclidine. Drug Metab Dispos 2003; 31:46-52.
99. Blobaum AL, Harris DL, Hollenberg PF. P450 active site architecture and reversibility:inactivation of cytochromes P450 2B4 and 2B4 T302A by tert-butyl acetylenes. Biochemistry 2005; 44:3831-3844.
100. Kobayashi Y, Sridar C, Kent UM, Puppali SG, Rimoldi JM, Zhang H, Waskell L, Hollenberg PF. Structure-activity relationship and elucidation of the determinant factor(s) responsible for the mechanism-based inactivation of cytochrome P450 2B6 by substituted phenyl diaziridines. Drug Metab Dispos 2006; 34:2102-2110.
101. Kent UM, Lin HL, Mills DE, Regal KA, Hollenberg PF. Identification of 17-alphaethynylestradiol- modified active site peptides and glutathione conjugates formed during metabolism and inactivation of P450s 2B1 and 2B6. Chem Res Toxicol 2006; 19:279-287.
102. Lin HL and Hollenberg PF. The inactivation of cytochrome P450 3A5 by 17a-ethynylestradiol is cytochrome b5-dependent: metabolic activation of the ethynyl moiety leads to the formation of glutathione conjugates, a heme adduct, and covalent binding to the apoprotein. J Pharmacol Exp Ther 2007; 321:276-287.
103. Masters BSS. The role of NADPH-cytochrome c (P-450) reductase in detoxication. In: Jakoby WB, ed. Enzymatic Basis of Detoxication, Vol. I. New York: Academic Press, 1980:183-200.
104. Yoshida T, Takahashi S, Kikuchi G. Partial purification and reconstitution of the heme oxygenase system from pig spleen microsomes. J Biochem 1974; 75:1187-1191.
105. Yasukochi Y, Masters BSS. Some properties of a detergent-solubilized NADPH-cytochrome c (cytochrome P-450) reductase purified by biospecific affinity chromatography. J Biol Chem 1976; 251:5337-5344.
106. Tew DG. Inhibition of cytochrome P450 reductase by the diphenyliodonium cation. Kinetic analysis and covalent modifications. Biochemistry 1993; 32:10209-10215.
107. Clement B, Weide M, Ziegler DM. Inhibition of purified and membrane-bound flavincontaining monooxygenase 1 by (N, N-dimethylamino)stilbene carboxylates. Chem Res Toxicol 1996; 9:599-604.
108. Hines RN, Cashman JR, Philpot RM, Williams DE, Ziegler DM. The mammalian flavincontaining monooxygenases: molecular charcterization and regulation of expression. Toxicol Appl Pharmacol 1994; 125:1-6.
109. Cashman JR. Monoamine oxidase and flavin-containing monooxygenases. In: Guengerich FP, ed. Biotransformation, Vol. 3, Comprehensive Toxicology. 1st ed. Oxford: Elsevier, 1997: 69-96.
110. Panoutsopoulos GI, Kouretas D, Beedham C. Contribution of aldehyde oxidase, xanthine oxidase, and aldehyde dehydrogenase on the oxidation of aromatic aldehydes. Chem Res Toxicol 2004; 17:1368-1376.
111. Rajagopalan KV. Xanthine dehydrogenase and aldehyde oxidase. In: Guengerich FP, ed. Biotransformation, Vol. 3, Comprehensive Toxicology. 1st ed. Oxford: Elsevier, 1997:165-178.
112. Dick RA, Kanne DB, Casida JE. Nitroso-imidacloprid irreversibly inhibits rabbit aldehyde oxidase. Chem Res Toxicol 2007; 20:1942-1946.
113. Petersen D, Lindahl R. Aldehyde dehydrogenases. In: Guengerich FP, ed. Biotransformation, Vol. 3, Comprehensive Toxicology. 1st ed. Oxford: Elsevier, 1997: 97-118.
114. Yamazaki H, Inui Y, Yun C-H, Mimura M, Guengerich FP, Shimada T. Cytochrome P450 2E1 and 2A6 enzymes as major catalysts for metabolic activation of N-nitrosodialkylamines and tobacco-related nitrosamines in human liver microsomes. Carcinogenesis 1992; 13:1789-1794.
115. Hart BW, Faiman MD. Bioactivation of S-methyl N, N-diethylthiolcarbamate to S-methyl N, N-diethylthiolcarbamate sulfoxide. Biochem Pharmacol 1993; 46:2285-2290.
116. Madan A, Parkinson A, Faiman MD. Identification of the human and rat P450 enzymes responsible for the sulfoxidation of S-methyl N, N-diethylthiolcarbamate (DETC-Me): the terminal step in the bioactivation of disulfiram. Drug Metab Dispos 1995; 23:1153-1162.
117. Flynn TG, Kubiseski TJ. Aldo-ketoreductases: structure, mechanism, and function. In:Guengerich FP, ed. Biotransformation, Vol. 3, Comprehensive Toxicology. 1st ed. Oxford:Elsevier, 1997:133-147.
118. Quinn DM. Esterases of the a/b hydrolase fold family. In: Guengerich FP, ed. Biotransformation, Vol. 3, Comprehensive Toxicology. 1st ed. Oxford: Elsevier, 1997:243-264.
119. Lacourciere GM, Armstrong RN. Microsomal and soluble epoxide hydrolases are members of the same family of C-X bond hydrolase enzymes. Chem Res Toxicol 1994; 7:121-124.
120. Lacourciere GM, Armstrong RN. The catalytic mechanism of microsomal epoxide hydrolase involves an ester intermediate. J Am Chem Soc 1993; 115:10466-10467.
121. Oesch F. Purification and specificity of a human microsomal epoxide hydratase. Biochem J 1974; 139:77-88.
122. Hammock BD, Grant DF, Storms DH. Epoxide hydrolases. In: Guengerich FP, ed. Biotransformation, Vol. 3, Comprehensive Toxicology. 1st ed. Oxford: Elsevier, 1997:283-305.
123. Jakoby WB, Habig WH. Glutathione transferases. In: Jakoby WB, ed. Enzymatic Basis of Detoxication, Vol. 2. New York: Academic Press, 1980:63-94.
124. Armstrong RN. Glutathione S-transferases: reaction mechanism, structure, and function. Chem Res Toxicol 1991; 4:131-140.
125. Litwack G, Ketterer B, Arias IM. Ligandin: a hepatic protein which binds steroids, bilirubin, carcinogens, and a number of exogenous anions. Nature 1971; 234:466-467.
126. Simons PC, Vander Jagt DL. Purification of glutathione S-transferases from human liver by glutathione-affinity chromatography. Anal Biochem 1977; 82:334-341.
127. Graminski GF, Kubo Y, Armstrong RN. Spectroscopic and kinetic evidence for the thiolate anion of glutathione at the active site of glutathione S-transferase. Biochemistry 1989; 28:3562-3568.
128. Adang AEP, Brussee J, van der Gen A, Mulder GJ. Inhibition of rat liver glutahione S-transferase isoenzymes by peptides stabilized against degradation by g-glutamyl transpeptidases. J Biol Chem 1991; 266:830-836.
129. Graminski GF, Zhang P, Sesay MA, Ammon HL, Armstrong RN. Formation of the 1-(S-glutathionyl)-2, 4, 6-trinitrocyclohexadienate anion at the active site of glutathione S-transferase: evidence for enzymic stabilization of s-complex intermediates in nucleophilic aromatic substitution reactions. Biochemistry 1989; 28:6252-6258.
130. Armstrong RN. Glutathione transferases. In: Guengerich FP, ed. Biotransformation, Vol. 3, Comprehensive Toxicology. 1st ed. Oxford: Elsevier, 1997:307-327.
131. Katusz RM, Bono B, Colman RF. Affinity labeling of Cys111 of glutathione S-transferase, isoenzyme 1-1, by S-(4-bromo-2, 3-dioxobutyl)glutathione. Biochemistry 1992; 31:8984-8990.
132. Ploemen JHTM, Johnson WW, Jespersen S, Vanderwall D, van Ommen B, van der Greef J, van Bladeren PJ, Armstrong RN. Active-site tyrosyl residues are targets in the irreversible inhibition of a class mu glutathione transferase by 2-(S-glutathionyl)-3, 5, 6-trichloro-1, 4- benzoquinone. J Biol Chem 1994; 269:26890-26897.
133. McTigre MA, Williams DR, Tainer JA. Crystal structures of a Schistomal drug vaccine target:Glutathione S-transferase from Schistoma japonica and its complex with the leading antischistosomal drug praziquantel. J Mol Biol 1995; 246:21-27.
134. Duffel MW. Sulfotransferases. In: Guengerich FP, ed. Biotransformation, Vol. 3, Comprehensive Toxicology. 1st ed. Oxford: Elsevier, 1997:365-383.
135. Burchell B, McGurk K, Brierly CH, Clarke DJ. UDP-glucuronosyltransferases. In: Guengerich FP, ed. Biotransformation, Vol. 3, Comprehensive Toxicology. 1st ed. Oxford: Elsevier, 1997:401-435.
136. Noort D, Coughtrie MWH, Burchell B, van der Morel GA, van Boom JH, van der Gen A, Mulder GJ. Inhibition of UDP-glucuronosyltransferase activity by possible transition state analogues in rat liver microsomes. Eur J Biochem 1990; 281:170.
137. Radominska A, Paul P, Treat S, Towbin H, Pratt C, Little J, Magdalou J, Lester R, Drake R. Photoaffinity labeling for evaluation of uridinyl analogs as specific inhibitors of rat liver UDPglucuronosyltransferase. Biochim Biophys Acta 1994; 1205:336.
138. 3H]flunitrazepam. Mol Pharmacol 1990; 38:294-298.
139. Xiong Y, Bernardi D, Bratton S, Ward MD, Battaglia E, Finel M, Drake RR, Radominska-Pandya A. Phenylalanine 90 and 93 are localized within the phenol binding site of human UDP-glucuronosyltransferase 1A10 as determined by photoaffinity labeling, mass spectrometry, and site-directed mutagenesis. Biochemistry 2006; 45:2322-2332.
140. Li AP, ed. Drug Interactions: Scientific and Regulatory Perspectives (Adv. Pharmacol. Series). San Diego: Academic Press, 1996.
141. Knodell RG, Browne D, Gwodz GP, Brian WR, Guengerich FP. Differential inhibition of human liver cytochromes P-450 by cimetidine. Gastroenterology 1991; 101:1680-1691.
142. Yun C-H, Okerholm RA, Guengerich FP. Oxidation of the antihistaminic drug terfenadine in human liver microsomes: role of cytochrome P450 3A(4) in N-dealkylation and C-hydroxylation. Drug Metab Dispos 1993; 21:403-409.
143. Kivistö KT, Neuvonen PJ, Klotz U. Inhibition of terfenadine metabolism: pharmacokinetic and pharmacodynamic consequences. Clin Pharmacokin 1994; 27:1-5.
144. Woosley RL, Chen Y, Freiman JP, Gillis RA. Mechanism of the cardiotoxic actions of terfenadine. J Am Med Assoc 1993; 269:1532-1536.
145. Stinson SC. Uncertain climate for antihistamines. Chem Eng News 1997; 75:43-45.
146. Ortiz de Montellano PR, Kunze KL, Yost GS, Mico BA. Self-catalyzed destruction of cytochrome P-450: covalent binding of ethynyl sterols to prosthetic heme. Proc Natl Acad Sci U S A 1979; 76:746-749.
147. Guengerich FP. Oxidation of 17a-ethynylestradiol by human liver cytochrome P-450. Mol Pharmacol 1988; 33:500-508.
148. Guengerich FP. Mechanism-based inactivation of human liver cytochrome P-450 IIIA4 by gestodene. Chem Res Toxicol 1990; 3:363-371.
149. Jung-Hoffmann C, Kuhl H. Pharmacokinetics and pharmacodynamics of oral contraceptive steroids: factors influencing steroid metabolism. Am J Obstet Gynecol 1990; 163:2183-2197.
150. Houston JB, Galetin A. Progress towards prediction of human pharmacokinetic parameters from in vitro technologies. Drug Metab Rev 2003; 35:393-415.
151. Shiran MR, Proctor NJ, Howgate EM, Rowland-Yeo K, Tucker GT, Rostami-Hodjegan A. Prediction of metabolic drug clearance in humans: in vitro-in vivo extrapolation vs allometric scaling. Xenobiotica 2006; 36:567-580.
152. Zhou S, Yung Chan S, Cher Goh B, Chan E, Duan W, Huang M, McLeod HL. Mechanismbased inhibition of cytochrome P450 3A4 by therapeutic drugs. Clin Pharmacokinet 2005; 44:279-304.