Mechanism of inactivation of human cytochrome P450 2b6 by phencyclidine

Drug Metabolism and Disposition

Volumn 34, Issue 9, 2006, Pages 1523-1529

  Jushchyshyn, Monica I ^a   Wahlstrom, Jan L ^a   Hollenberg, Paul F ^b   Wienkers, Larry C ^a,c  

^a PFIZER INC   (United States)

^b UNIVERSITY OF MICHIGAN MEDICAL SCHOOL   (United States)

^c AMGEN INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CYCLOHEXANE; CYTOCHROME P450; CYTOCHROME P450 2B6; CYTOCHROME P450 2C19; CYTOCHROME P450 2D6; CYTOCHROME P450 3A4; GLUTATHIONE; PHENCYCLIDINE; PIPERIDINE;

ARTICLE; CATALYSIS; CONTROLLED STUDY; DRUG CONJUGATION; DRUG MECHANISM; DRUG OXIDATION; DRUG STRUCTURE; ENZYME INACTIVATION; FENTON REACTION; HUMAN; HUMAN CELL; LIQUID CHROMATOGRAPHY; MASS SPECTROMETRY; PRIORITY JOURNAL;

ARYL HYDROCARBON HYDROXYLASES; ENZYME INHIBITORS; GLUTATHIONE; HUMANS; HYDROGEN PEROXIDE; HYDROXYLATION; IRON; MIXED FUNCTION OXYGENASES; OXIDATION-REDUCTION; OXIDOREDUCTASES, N-DEMETHYLATING; PHENCYCLIDINE; PROTEIN BINDING; RECOMBINANT PROTEINS;

EID: 33747824131     PISSN: 00909556     EISSN: 1521009X     Source Type: Journal    
DOI: 10.1124/dmd.106.010579     Document Type: Article

References (30)

1. Atkinson JK and Ingold KU (1993) Cytochrome P450 hydroxylation of hydrocarbons: variation in the rate of oxygen rebound using cyclopropyl radical clocks including two new ultrafast probes. Biochemistry 32:9209-9214.
2. Bowry V, Lusztyk J, and Ingold KU (1990) Calibration of very fast alkyl radical "clock" rearrangements using nitroxides. Pure Appl Chem 62:213-216.
3. Castagnoli N Jr, Rimoldi JM, Bloomquist J, and Castagnoli KP (1997) Potential metabolic bioactivation pathways involving cyclic tertiary amines and azaarenes. Chem Res Toxicol 10:924-940.
4. Chen Q, Ngui JS, Doss GA, Wang RW, Cai X, DiNinno FP, Blizzard TA, Hammond ML, Stearns RA, Evans DC, et al. (2002) Cytochrome P450 3A4-mediated bioactivation of raloxifene: irreversible enzyme inhibition and thiol adduct formation. Chem Res Toxicol 15:907-914.
5. Groves JT and McClusky GA (1976) Aliphatic hydroxylation via oxygen rebound. Oxygen transfer catalyzed by iron. J Am Chem Soc 98:859-861.
6. Heur Y-H, Streeter AJ, Nims RW, and Keefer LK (1989) The Fenton degradation as a nonenzymatic model for microsomal denitrosation of N-nitrosodimethylamine. Chem Res Toxicol 2:247-253.
7. Hoag MK, Trevor AJ, Asscher Y, Weissman J, and Castagnoli N (1984) Metabolism-dependent inactivation of liver microsomal enzymes by phencyclidine. Drug Metab Dispos 12:371-375.
8. Holsztynska EJ and Domino EF (1985) Biotransformation of phencyclidine. Drug Metab Rev 16:285-320.
9. Jushchyshyn MI, Kent UM, and Hollenberg PF (2003) The mechanism-based inactivation of human cytochrome P450 2B6 by phencyclidine. Drug Metab Dispos 31:46-52.
10. Lewis DF, Lake BG, Dickins M, Eddershaw PJ, Tarbit MH, and Goldfarb PS (1999) Molecular modeling of CYP2B6, the human CYP2B isoform, by homology with the substrate-bound CYP102 crystal structure: evaluation of CYP2B6 substrate characteristics, the cytochrome B5 binding site and comparisons with CYP2B1 and CYP2B4. Xenobiotica 29:361-393.
11. Maldotti A, Bartocci C, Varani G, Molinari A, Battioni P, and Mansuy D (1996) Oxidation of cyclohexane by molecular oxygen photoassisted by meso-teraarylporphyrin iron(III)-hydroxo complexes. Inorg Chem 35:1126-1131.
12. Masumoto H, Takeuchi K, Ohta S, and Hirobe M (1989) Application of chemical P450 model systems to studies on drug metabolism. I. Phencyclidine: a multi-functional model substrate. Chem Pharm Bull 37:1788-1794.
13. O'Neill P, Bishop LP, Searle NL, Maggs JL, Storr RC, Ward SA, Park BK, and Mabbs F (2000) Biomimetic Fe(II)-mediated degradation of arteflene (Ro-42-1611). The first EPR spin-trapping evidence for the previously postulated secondary carbon-centered cyclohexyl radical. J Org Chem 65:1578-1582.
14. Osawa Y and Coon MJ (1989) Selective mechanism-based inactivation of the major phenobarbital-inducible P450 cytochrome from rabbit liver by phencyclidine and its oxidation product, the iminium compound. Drug Metab Dispos 17:7-13.
15. Osawa Y, Davila JC, Nakatsuka M, Meyer CA, and Darbyshire JF (1995) Inhibition of P450 cytochromes by reactive intermediates. Drug Metab Rev 27:61-72.
16. Peng JZ, Remmel RP, and Sawchuk RJ (2004) Inhibition of murine cytochrome P4501A by tacrine: in vitro studies. Drug Metab Dispos 32:805-812.
17. Reis A, Domingues MRM, and Amado FML (2003) Detection and characterization by mass spectrometry of radical adducts produced by linoleic acid oxidation. J Am Soc Mass Spectrom 14:1250-1261.
18. Reis A, Domingues P, Ferrer-Correia AJ, and Domingues MRM (2004) Identification by electrospray tandem mass spectrometry of spin-trapped free radicals from oxidized 2-oleoyl-1-palmitoyl-sn-glycero-3-phosphocholine. Rapid Commun Mass Spectrom 18:1047-1058.
19. Rota C, Barr DP, Martin MV, Guengerich FP, Tomasi A, and Mason RP (1997) Detection of free radicals produced from the reaction of cytochrome P-450 with linoleic acid hydroperoxide. Biochem J 328:565-571.
20. Sayre LM, Engelhart DA, Nadkarni DV, Manoj Babu MK, Flammang AM, and McCoy GD (1997) The role of iminium-enamine species in the toxication and detoxication of cyclic tertiary amines. NIDA Res Monogr 17:106-127.
21. Sayre LM, Engelhart DA, Venkataraman B, Babu MK, and McCoy GD (1991) Generation and fate of enamines in the microsomal metabolism of cyclic tertiary amines. Biochem Biophys Res Commun 179:1368-1376.
22. Shaik S, de Visser SP, Ogliaro F, Schwarz H, and Schroder D (2002) Two-state reactivity mechanisms of hydroxylation and epoxidation by cytochrome P-450 revealed by theory. Curr Opin Chem Biol 6:556-567.
23. Shebley M, Jushchyshyn MI, and Hollenberg PF (2006) Selective pathways for the metabolism of phencyclidine by cytochrome P450 2B enzymes: identification of electrophilic metabolites, glutathione and N-acetyl cysteine adducts. Drug Metab Dispos 34:375-383.
24. Tang C, Subramanian R, Kuo Y, Krymgold S, Lu P, Kuduk SD, Ng C, Feng D-M, Elmore C, Soli E, et al. (2005) Bioactivation of 2,3-diaminopyridine-containing bradykinin B1 receptor antagonists: irreversible binding to liver microsomal proteins and formation of glutathione conjugates. Chem Res Toxicol 18:934-945.
25. Wang Q and Halpert JR (2002) Combined three-dimensional quantitative structure-activity relationship analysis of cytochrome P450 2B6 substrates and protein homology modeling. Drug Metab Dispos 30:86-95.
26. Ward D, Kalir A, Trevor A, Adams J, Baillie T, and Castagnoli N Jr (1982a) Metabolic formation of iminium species: metabolism of phencyclidine. J Med Chem 25:491-492.
27. Ward DP, Trevor AJ, Kalir A, Adams JD, Baillie TA, and Castagnoli N (1982b) Metabolism of phencyclidine: the role of iminium ion formation in covalent binding to rabbit microsomal protein. Drug Metab Dispos 10:690-695.
28. Wardman P and Candeias LP (1996) Fenton chemistry: an introduction. Radiat Res 145:523-531.
29. Zbaida S and Kariv R (1990) Simulation of the hepatic metabolism of stilbene and its tricyclic derivatives by Fenton and ruff reagents: models for cytochrome P-450 activation of chemical carcinogens. Biopharm Drug Dispos 2:39-51.
30. Zbaida S, Kariv R, and Fischer P (1988) The role of iron chelates on the selectivity of Fenton reagent in hydroxylation, N-demethylation, and sulfoxidation of cimetidine: a novel biomemietic model for the regioselectivity of cytochrome P-450. Arch Biochem Biophys 261:12-15.