Differential time-dependent inactivation of P450 3A4 and P450 3A5 by raloxifene: A key role for C239 in quenching reactive intermediates

Chemical Research in Toxicology

Volumn 20, Issue 12, 2007, Pages 1778-1786

  Pearson, Josh T ^a   Wahlstrom, Jan L ^a   Dickmann, Leslie J ^a   Kumar, Santosh ^b   Halpert, James R ^b   Wienkers, Larry C ^a   Foti, Robert S ^a   Rock, Dan A ^a,c  

^a AMGEN INC   (United States)

^b University of Texas Medical Branch School of Medicine   (United States)

^c NONE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CYSTEINE; CYTOCHROME P450 3A4; CYTOCHROME P450 3A5; MIDAZOLAM; RALOXIFENE; TESTOSTERONE;

ARTICLE; COMPUTER MODEL; COVALENT BOND; DNA ADDUCT; ENZYME ACTIVE SITE; ENZYME INACTIVATION; ENZYME INHIBITION; GENETIC SUSCEPTIBILITY; IC 50; MINIMUM INHIBITORY CONCENTRATION; PHARMACOGENETICS; PHOTOCHEMICAL QUENCHING;

CLONING, MOLECULAR; CYSTEINE; CYTOCHROME P-450 ENZYME SYSTEM; ESCHERICHIA COLI; HUMANS; MODELS, MOLECULAR; MUTATION; RALOXIFENE; SELECTIVE ESTROGEN RECEPTOR MODULATORS; TIME FACTORS;

EID: 38149048655     PISSN: 0893228X     EISSN: None     Source Type: Journal    
DOI: 10.1021/tx700207u     Document Type: Article

References (36)

1. Mahgoub, A., Idle, J. R., Dring, L. G., Lancaster, R., and Smith, R. L. (1977) Polymorphic hydroxylation of Debrisoquine in man. Lancet 2, 584-586.
2. m) and loss of stereoselectivity of bufuralol 1′-hydroxylation in poor metabolizers. Biochem. Biophys. Res. Commun. 125, 374-380.
3. Tucker, G. T., Silas, J. H., Iyun, A. O., Lennard, M. S., and Smith, A. J. (1977) Polymorphic hydroxylation of debrisoquine. Lancet 2, 718.
4. Idle, J. R., Mahgoub, A., Lancaster, R., and Smith, R. L. (1978) Hypotensive response to debrisoquine and hydroxylation phenotype. Life Sci. 22, 979-983.
5. Bradford, L. D. (2002) CYP2D6 allele frequency in European Caucasians, Asians, Africans and their descendants. Pharmacogenomics 3, 229-243.
6. Heimark, L. D., Wienkers, L., Kunze, K., Gibaldi, M., Eddy, A. C., Trager, W. F., O'Reilly, R. A., and Goulart, D. A. (1992) The mechanism of the interaction between amiodarone and warfarin in humans. Clin. Pharmacol. Ther. 51, 398-407.
7. Steward, D. J., Haining, R. L., Henne, K. R., Davis, G., Rushmore, T. H., Trager, W. F., and Rettie, A. E. (1997) Genetic association between sensitivity to warfarin and expression of CYP2C9*3. Pharmacogenetics 7, 361-367.
8. Becking, G. C. (1995) Use of mechanistic information in risk assessment for toxic chemicals. Toxicol. Lett. 77, 15-24.
9. Shimada, T., Yamazaki, H., Mimura, M., Inui, Y., and Guengerich, F. P. (1994) Interindividual variations in human liver cytochrome P-450 enzymes involved in the oxidation of drugs, carcinogens and toxic chemicals: studies with liver microsomes of 30 Japanese and 30 Caucasians. J. Pharmacol. Exp. Ther. 270, 414-423.
10. Wrighton, S. A., Brian, W. R., Sari, M. A., Iwasaki, M., Guengerich, F. P., Raucy, J. L., Molowa, D. T., and Vandenbranden, M. (1990) Studies on the expression and metabolic capabilities of human liver cytochrome P450IIIA5 (HLp3). Mol. Pharmacol. 38, 207-213.
11. Lin, Y. S., Dowling, A. L., Quigley, S. D., Farin, F. M., Zhang, J., Lamba, J., Schuetz, E. G., and Thummel, K. E. (2002) Co-regulation of CYP3A4 and CYP3A5 and contribution to hepatic and intestinal midazolam metabolism. Mol. Pharmacol. 62, 162-172.
12. Khan, K. K., He, Y. Q., Correia, M. A., and Halpert, J. R. (2002) Differential oxidation of mifepristone by cytochromes P450 3A4 and 3A5: selective inactivation of P450 3A4. Drug Metab. Dispos. 30, 985-990.
13. McConn, D. J., 2nd, Lin, Y. S., Allen, K., Kunze, K. L., and Thummel, K. E. (2004) Differences in the inhibition of cytochromes P450 3A4 and 3A5 by metabolite-inhibitor complex-forming drugs. Drug Metab. Dispos. 32, 1083-1091.
14. Wang, Y. H., Jones, D. R., and Hall, S. D. (2005) Differential mechanism-based inhibition of CYP3A4 and CYP3A5 by verapamil. Drug Metab. Dispos. 33, 664-671.
15. Baer, B. R., Wienkers, L. C., and Rock, D. A. (2007) Time-dependent inactivation of P450 3A4 by raloxifene; identification of Cys239 as the site of apoprotein alkylation. Chem. Res. Toxicol. 20, 954-264.
16. Gillam, E. M., Baba, T., Kim, B. R., Ohmori, S., and Guengerich, F. P. (1993) Expression of modified human cytochrome P450 3A4 in Escherichia coli and purification and reconstitution of the enzyme. Arch. Biochem. Biophys. 305, 123-131.
17. Domanski, T. L., He, Y. A., Khan, K. K., Roussel, F., Wang, Q., and Halpert, J. R. (2001) Phenylalanine and tryptophan scanning mutagenesis of CYP3A4 substrate recognition site residues and effect on substrate oxidation and cooperativity. Biochemistry 40, 10150-10160.
18. 5 and studies on their mechanism of function. Arch. Biochem. Biophys. 312, 554-565.
19. Rock, D., Rock, D., and Jones, J. P. (2001) Inexpensive purification of P450 reductase and other proteins using 2′,5′-adenosine diphosphate agarose affinity columns. Protein Expression Purif. 22, 82-83.
20. Yano, J. K., Wester, M. R., Schoch, G. A., Griffin, K. J., Stout, C. D., and Johnson, E. F. (2004) The structure of human microsomal cytochrome P450 3A4 determined by X-ray crystallography to 2.05-Å resolution. J. Biol. Chem. 279, 38091-38094.
21. 5. Arch. Biochem. Biophys. 348, 107-115.
22. 1 metabolism as a probe. Biochemistry 37, 12536-12545.
23. Yu, L., Liu, H., Li, W., Zhang, F., Luckie, C., van Breemen, R. B., Thatcher, G. R., and Bolton, J. L. (2004) Oxidation of raloxifene to quinoids: potential toxic pathways via a diquinone methide and o-quinones. Chem. Res. Toxicol. 17, 879-888.
24. Chen, Q., Ngui, J. S., Doss, G. A., Wang, R. W., Cai, X., DiNinno, F. P., Blizzard, T. A., Hammond, M. L., Stearns, R. A., Evans, D. C., Baillie, T. A., and Tang, W. (2002) Cytochrome P450 3A4-mediated bioactivation of raloxifene: irreversible enzyme inhibition and thiol adduct formation. Chem. Res. Toxicol. 15, 907-914.
25. Hasemann, C. A., Kurumbail, R. G., Boddupalli, S. S., Peterson, J. A., and Deisenhofer, J. (1995) Structure and function of cytochromes P450: a comparative analysis of three crystal structures. Structure 3, 41-62.
26. 1 oxidation. Chem. Res. Toxicol. 14, 483-491.
27. Coles, B. (1984) Effects of modifying structure on electrophilic reactions with biological nucleophiles. Drug Metab. Rev. 15, 1307-1334.
28. Mutlib, A. E., Goosen, T. C., Bauman, J. N., Williams, J. A., Kulkarni, S., and Kostrubsky, S. (2006) Kinetics of acetaminophen glucuronidation by UDP-glucuronosyltransferases 1A1, 1A6, 1A9, and 2B15. Potential implications in acetaminophen-induced hepatotoxicity. Chem. Res. Toxicol. 19, 701-709.
29. Stark, K. L., Harris, C., and Juchau, M. R. (1989) Influence of electrophilic character and glutathione depletion on chemical dysmorphogenesis in cultured rat embryos. Biochem. Pharmacol. 38, 2685-2692.
30. Argoti, D., Liang, L., Conteh, A., Chen, L., Bershas, D., Yu, C. P., Vouros, P., and Yang, E. (2005) Cyanide trapping of iminium ion reactive intermediates followed by detection and structure identification using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Chem. Res. Toxicol. 18, 1537-1544.
31. Schnetz-Boutaud, N., Daniels, J. S., Hashim, M. F., Scholl, P., Burrus, T., and Marnett, L. J. (2000) Pyrimido[1,2-α]purin-10(3H)-one: a reactive electrophile in the genome. Chem. Res. Toxicol. 13, 967-970.
32. Zhou, S., Chan, E., Lim, L. Y., Boelsterli, U. A., Li, S. C., Wang, J., Zhang, Q., Huang, M., and Xu, A. (2004) Therapeutic drugs that behave as mechanism-based inhibitors of cytochrome P450 3A4. Curr. Drug Metab. 5, 415-442.
33. Wojnowski, L., Turner, P. C., Pedersen, B., Hustert, E., Brockmoller, J., Mendy, M., Whittle, H. C., Kirk, G., and Wild, C. P. (2004) Increased levels of aflatoxin-albumin adducts are associated with CYP3A5 polymorphisms in The Gambia, West Africa. Pharmacogenetics 14, 691-700.
34. Anderson, B. M., Cordes, E. H., and Jencks, W. P. (1961) Reactivity and catalysis in reactions of the serine hydroxyl group and of O-acyl serines. J. Biol. Chem. 236, 455-463.
35. Melet, A., Assrir, N., Jean, P., Pilar Lopez-Garcia, M., Marques-Soares, C., Jaouen, M., Dansette, P. M., Sari, M. A., and Mansuy, D. (2003) Substrate selectivity of human cytochrome P450 2C9: importance of residues 476, 365, and 114 in recognition of diclofenac and sulfaphenazole and in mechanism-based inactivation by tienilic acid. Arch. Biochem. Biophys. 409, 80-91.
36. Yano, J. K., Denton, T. T., Cerny, M. A., Zhang, X., Johnson, E. F., and Cashman, J. R. (2006) Synthetic inhibitors of cytochrome P-450 2A6: inhibitory activity, difference spectra, mechanism of inhibition, and protein cocrystallization. J. Med. Chem. 49, 6987-7001.