Mechanism-based inactivation of cytochrome P-450-3A4 by mifepristone (RU486)

Journal of Pharmacology and Experimental Therapeutics

Volumn 288, Issue 2, 1999, Pages 791-797

  He, Kan ^a   Woolf, Thomas F ^b   Hollenberg, Paul F ^a  

^a UNIVERSITY OF MICHIGAN MEDICAL SCHOOL   (United States)

^b PFIZER INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANTIGESTAGEN; CYTOCHROME P450; MIFEPRISTONE; TESTOSTERONE;

ABORTION; ARTICLE; COMPETITIVE INHIBITION; COVALENT BOND; DRUG MECHANISM; ENZYME ACTIVE SITE; ENZYME INACTIVATION; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; HYDROXYLATION; NONHUMAN; PRIORITY JOURNAL; PROTEIN MODIFICATION; STOICHIOMETRY;

BIOLOGY; CLINICAL RESEARCH; ENDOCRINE SYSTEM; ENZYMES AND ENZYME INHIBITORS; EXAMINATIONS AND DIAGNOSES; HORMONE ANTAGONISTS; HORMONES; LABORATORY EXAMINATIONS AND DIAGNOSES; LABORATORY PROCEDURES; METABOLIC EFFECTS; PHYSIOLOGY; RESEARCH METHODOLOGY; RESEARCH REPORT; RU-486;

ABORTIFACIENT AGENTS, STEROIDAL; ANIMALS; APOENZYMES; CHROMATOGRAPHY, HIGH PRESSURE LIQUID; CYTOCHROME P-450 ENZYME SYSTEM; ELECTROPHORESIS, POLYACRYLAMIDE GEL; ENZYME ACTIVATION; HEME; HUMANS; KINETICS; MALE; MIFEPRISTONE; MIXED FUNCTION OXYGENASES; NADP; RATS; RATS, INBRED F344; SODIUM DODECYL SULFATE; SPECTRUM ANALYSIS; TESTOSTERONE;

EID: 0033061072     PISSN: 00223565     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Article

References (39)

1. Cai Y, Baer-Dubowska W, Ashwood-Smith MJ, Ceska O, Tachibana S and DiGiovanni J (1996) Mechanism-based inactivation of hepatic ethoxyresorufin O-dealkylation activity by naturally occurring coumarins. Chem Res Toxicol 9:729-736.
2. Chan WK, Sui Z, and Ortiz de Montellano PR (1993) Determination of protein modification versus heme alkylation: Inactivation of cytochrome P450 1A1 by 1-ethynylpyrene and phenylacetylene. Chem Res Toxicol 6:38-45.
3. Chasserot-Golaz S, Ribeiro V, Genot G, Lechner MC and Beck G (1990) The steroid antagonist RU38486 is metabolized by the liver microsomal P450 monooxygenases. Biochem Biophys Res Commun 167:1271-1278.
4. Foroozesh M, Primrose G, Guo Z, Bell LC, Alworth WL and Guengerich FP (1997) Aryl acetylenes as mechanism-based inhibitors of cytochrome P450-dependent monooxygenase enzymes. Chem Res Toxicol 10:91-102.
5. Frye LL and Robinson CH (1990) Synthesis of potential mechanism-based inactivators of lanosterol 14α-demethylase. J Org Chem 55:1579-1584.
6. Gan LSL, Acebo AL and Alworth WL (1984) 1-Ethylnylpyrene, a suicide inhibitor of cytochrome P-450 dependent benzo(a)pyrene hydroxylase activity in liver microsomes. Biochemistry 23:3827-3836.
7. Gillam EM, Baba T, Kim BR, Ohmori S and Guengerich FP (1993) Expression of modified human cytochrome P450 3A4 in Escherichia coli. and purification and reconstitution of the enzyme. Arch Biochem Biophys 305:123-131.
8. Gruol DJ, Zee MC, Trotter J and Bourgeois S (1994) Reversal of multidrug resistance by RU486. Cancer Res 54:3088-3091.
9. Guengerich FP (1990) Mechanism-based inactivation of human liver microsomal cytochrome P-450 IIIA4 by gestodene. Chem Res Toxicol 3:363-371.
10. Halpert J, Hammond D and Neal RA (1980) Inactivation of purified rat liver cytochrome P-450 during the metabolism of parathion (diethyl p-nitrophenyl phosphorothionate). J Biol Chem 255:1080-1089.
11. Halpert J (1982) Further studies of the suicide inactivation of purified rat liver cytochrome P450 by chloramphenicol. Mol Pharmacol 21:166-172.
12. He K, Falick AM, Chen B, Nilsson F and Correia MA (1996a) Identification of the heme adduct and an active site peptide modified during mechanism-based inactivation of rat liver cytochrome P450 2B1 by secobarbital. Chem Res Toxicol 9:614-622.
13. He K, He YA, Szklarz GD, Halpert JR and Correia MA (1996b) Secobarbital-mediated inactivation of cytochrome P450 2B1 and its active site mutants: Partitioning between heme and protein alkylation and epoxidation. J Biol Chem 271: 25864-25872.
14. He K, Iyer KR, Hayes RN, Sinz MW, Woolf TF and Hollenberg PF (1998) Inactivation of cytochrome P450 3A4 by bergamottin, a component of grapefruit juice. Chem Res Toxicol 11:252-259
15. Helvig C, Alayrac C, Mioskowski C, Koop D, Poullain D, Durst F and Salaun JP (1997) Suicide inactivation of cytochrome P450 by midchain and terminal acetylenes - a mechanistic study of inactivation of a plant acid ω-hydroxylase. J Biol Chem 272:414-421.
16. Jang GR, Wrighton SA and Benet LZ (1996) Identification of CYP3A4 as the principle enzyme catalyzing mifepristone (RU486) oxidation in human liver microsomes. Biochem Pharmacol 52:753-761.
17. Kent UM, Bend JR, Charmberlin BA, Gage DA and Hollenberg PF (1997) Mechanism-based inactivation of cytochrome P450 2B1 by N-benzyl-1-aminobenzotriazole. Chem Res Toxicol 10:600-608.
18. Kunze KL, Mangold BLK, Wheeler C, Beilan HS and Ortiz de Montellano PR (1983) The cytochrome P450 active site: Regiospecificity of prosthetic heme alkylation by olefins and acetylenes. J Biol Chem 258:4202-4207.
19. Labbe G, Descatiore V, Beaune P, Letteron P, Larrey D and Pessayre D (1989) Suicide inactivation of cytochrome P-450 by methoxypsoralen: Evidence for the covalent binding of a reactive intermediate to the protein moiety. J Pharmacol Exp Ther 250:1034-1042.
20. Lecureur V, Fardel O and Guilouzo A (1994) The antiprogestin drug RU486 potentiates doxorubicin cytotoxicity in multidrug resistant cells through inhibition of P-glycoprotein function. FEBS Lett 355:187-1991.
21. Lown K S, Bailey DG, Fontana RJ, Janardan SK, Adair CH, Fortlage LA, Brown MB, Guo W and Watkins PB (1997) Grapefruit juice increases felodipine oral bioavailability in humans by decreasing intestinal CYP3A protein expression. J Clin Invest 99:1-9.
22. Marcotte PA and Robinson CH (1982) Design of mechanism-based inactivators of human placental aromatase. Cancer Res 42:3322-3325.
23. Mays DC, Hilliard JB, Wong DD, Chambers MA, Park SS, Gelboin HV and Gerber N (1990) Bioactivation of 8-methoxypsoralen and irreversible inactivation of cytochrome P-450 in mouse liver microsomes: Modification by monoclonal antibodies, inhibition of drug metabolism and distribution of covalent adducts. J Pharmacol Exp Ther 254:720-731.
24. Nerurkar PV, Park SS, Thomas PE, Nims RW and Lubet RA (1993) Methoxyresorufin and benzyloxyresorufin: Substrates preferentially metabolized by cytochrome P450 1A2 and 2B, respectively, in the rat and mouse. Biochem Pharmacol 46:933-943.
25. Omura T and Sato R (1964) The carbon-monoxide binding pigment of liver microsomes. J Biol Chem 239:2370-2378.
26. Ortiz de Montellano PR and Correia MA (1995) Inhibition of cytochrome P450, in Cytochrome P450 - Structure, Mechanism and Biochemistry (Ortiz de Montellano PR ed) pp 305-366, Plenum Press, New York.
27. Ortiz de Montellano PR and Kunze KL (1981) Cytochrome P450 inactivation: structure of the prosthetic heme adduct with propyne. Biochemistry 20:7266-7271.
28. Reinke LA and Moyer MJ (1985) p-Nitrophenol hydroxylation, a microsomal oxidation which is highly inducible by ethanol. Drug Metab Dispos 13:548-552.
29. Roberts ES, Alworth WL and Hollenberg PF (1998) Mechanism-based inactivation of cytochrome P450 2E1 and 2B1 by 5-phenyl-1-pentyne. Arch Biochem Biophys 354:295-302.
30. Roberts ES, Hopkins NE, Alworth DA and Hollenberg PF (1993) Mechanism-based inactivation of cytochrome P450 2B1 by 2-ethynylnaphthalene: Identification of an active-site peptide. Chem Res Toxicol 6:470-479.
31. 3H-labeled 2-ethynylnaphthalene-inactivated P450 2B1 and 2B4 using amino acid sequencing and mass spectrometry. Biochemistry 33:3766-3771.
32. Sahali-Sahly Y, Balani SK, Lin JH and Baillie TA (1996) In vitro studies on the metabolic activation of the furanopyridine L-754,394, a highly potent and selective mechanism-based inhibitor of cytochrome P450 3A4. Chem Res Toxicol 9:1007-1012.
33. Schmiedlin-Ren P, Edwards DJ, Fitzsimmons ME, He K, Lown KS, Woster PM, Rahman A, Thummel KE, Fisher JM, Hollenberg PF and Watkins PB (1997) Mechanisms of enhanced oral availability of CYP3A4 substrates by grapefruit constituents - decreased enterocyte CYP 3A4 concentration and mechanism-based inactivation by furanocoumarins. Drug Metab Dispos 25:1228-1233
34. Sonderfan AJ, Arlotto MP, Dutton DR, McMillen SK and Parkinson A (1987) Regulation of testosterone hydroxylation by rat liver microsomal cytochrome P-450. Arch Biochem Biophys 255:27-41.
35. Spitz JM and Bardin CW (1993) Mifepristone (RU486) - a modulator of progestin and glucocorticoid action. N Engl J Med 329:404-486.
36. Strobel HW and Dignam JD (1978) Purification and properties of NADPH-cytochrome P450 reductase. Methods Enzymol 52:89-92.
37. Walsh CT (1984) Suicide substrates, mechanism-based enzyme inactivation: Recent developments. Ann Rev Biochem 53:493-535.
38. Waxman DJ and Walsh C (1982) Phenobarbital-induced rat liver cytochrome P450. J Biol Chem 257:10446-10457.
39. Yun CH, Hammons GJ, Jones G, Martin MV, Hopkins NE, Alworth WL and Guengerich FP (1992) Modification of cytochrome P450 1A2 enzymes by the mechanistic inactivator 2-ethynylnaphthalene and the photoaffinity label 4-azidobiphenyl. Biochemistry 33:3766-3771.