Cytochrome P450s and other enzymes in drug metabolism and toxicity

AAPS Journal

Volumn 8, Issue 1, 2006, Pages E101-E111

  Guengerich, F Peter ^a  

^a VANDERBILT UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

Cytochrome P450; Drug metabolism; Reactive metabolites; Toxicity

Indexed keywords

AFLATOXIN B1; BENOXAPROFEN; BETA LACTAM ANTIBIOTIC; CORTICOTROPIN; CYTOCHROME P450; DACARBAZINE; DANTROLENE; DAUNORUBICIN; DIHYDRALAZINE; DRUG; DRUG METABOLITE; DRUG METABOLIZING ENZYME; EPOXIDE; FELBAMATE; FEXOFENADINE; FLUTAMIDE; IPRONIAZID; ISONIAZID; KETOCONAZOLE; METHOXYRESORUFIN; NEFAZODONE; PARACETAMOL; PENICILLIN DERIVATIVE; RESORUFIN DERIVATIVE; TERFENADINE; TIENILIC ACID; TOLCAPONE; TRICHLOROETHYLENE; TROGLITAZONE; UNCLASSIFIED DRUG; UNINDEXED DRUG;

ARTICLE; CATALYST; DRUG ABSORPTION; DRUG ACTIVATION; DRUG BINDING; DRUG BIOAVAILABILITY; DRUG BLOOD LEVEL; DRUG DISTRIBUTION; DRUG EFFECT; DRUG EXCRETION; DRUG HYPERSENSITIVITY; DRUG MANUFACTURE; DRUG METABOLISM; DRUG RESEARCH; DRUG STRUCTURE; DRUG TOXICITY; GENOTOXICITY; HUMAN; IMMUNE RESPONSE; NONHUMAN; PATHOPHYSIOLOGY; TOXIC HEPATITIS; TOXICOKINETICS; UNSPECIFIED SIDE EFFECT; ANIMAL; CHEMICALLY INDUCED DISORDER; CHEMISTRY; CLASSIFICATION; METABOLISM; METHODOLOGY; PHARMACEUTICS; REVIEW;

ANIMALS; CYTOCHROME P-450 ENZYME SYSTEM; DRUG TOXICITY; HUMANS; PHARMACEUTICAL PREPARATIONS; TECHNOLOGY, PHARMACEUTICAL;

EID: 33645050104     PISSN: 15507416     EISSN: None     Source Type: Journal    
DOI: 10.1208/aapsj080112     Document Type: Article

References (58)

1. Guengerich FP. Cytochrome P450: what have we learned and what are the future issues? 2003 North American Region ISSX Scientific Achievement Award. Drug Metab Rev. 2004;36:159-197.
2. Guengerich FP. Human cytochrome P450 enzymes. In: Ortiz de Montellano PR, ed. Cytochrome P450: Structure, Mechanism, and Biochemistry. 3rd ed. New York, NY: Kluwer Academic/Plenum Press; 2005:377-531.
3. Guengerich FP, Wu Z-L, Bartleson CJ. Function of human cytochrome P450s: characterization of the remaining orphans. Biochem Biophys Res Commun. 2005;338:465-469.
4. Nebert DW, Russell DW. Clinical importance of the cytochromes P450. Lancet. 2002;360:1155-1162.
5. i/AUC ratios. Drug Metab Dispos. 2004;32:1201-1208.
6. Wienkers LC, Heath TG. Predicting in vivo drug interactions from in vitro drug discovery data. Nat Rev Drug Discov. 2005;4:825-833.
7. Guengerich FP. Cytochrome P450 oxidations in the generation of reactive electrophiles: epoxidations and related reactions. Arch Biochem Biophys. 2003;409:59-71.
8. Josephy PD, Guengerich FP, Miners JO. Phase 1 and phase 2 drug metabolism: terminology that we should phase out. Drug Metab Dispos. 2005;37:579-584.
9. Fahey JW, Zhang Y, Talalay P. Broccoli sprouts: an exceptionally rich source of inducers of enzymes that protect against chemical carcinogens. Proc Natl Acad Sci USA. 1997;94:10367-10372.
10. Monks TJ, Anders MW, Dekant W, Stevens JL, Lau SS, van Bladeren PJ. Glutathione conjugate mediated toxicities. Toxicol Appl Pharmacol. 1990; 106:1-19.
11. Wood AW, Levin W, Lu AYH, et al. Metabolism of benzo[a]pyrene and benzo[a]pyrene derivatives to mutagenic products by highly purified hepatic microsomal enzymes. J Biol Chem. 1976;251:4882-4890.
12. Miyata M, Kudo G, Lee YH, et al. Targeted disruption of the microsomal epoxide hydrolase gene: microsomal epoxide hydrolase is required for the carcinogenic activity of 7,12-dimethylbenz[a]anthracene. J Biol Chem. 1999;274:23963-23968.
13. Guengerich FP. Activation of dihaloalkanes by thiol-dependent mechanisms. J Biochem Mol Biol. 2003;36:20-27.
14. Miller JA, Surh YJ. Historical perspectives on conjugation-dependent bioactivation of foreign compounds. Adv Pharmacol. 1994;27:1-16.
15. Liebler DC, Guengerich FP. Elucidating mechanisms of drug-induced toxicity. Nat Rev Drug Discov. 2005;4:410-420.
16. Johnson TE, Zhang X, Bleicher KB, et al. Statins induce apoptosis in rat and human myotube cultures by inhibiting protein geranylgeranylation but not ubiquinone. Toxicol Appl Pharmacol. 2004;200:237-250.
17. Uetrecht JP. New concepts in immunology relevant to idiosyncratic drug reactions: the "danger hypothesis" and innate immune system. Chem Res Toxicol. 1999;12:387-395.
18. Kalgutkar AS, Soglia JR. Minimising the potential for metabolic activation in drug discovery. Expert Opin Drug Metab Toxicol. 2005;1:91-141.
19. 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.
20. Woosley RL, Chen Y, Freiman JP, Gillis RA. Mechanism of the cardiotoxic actions of terfenadine. JAMA. 1993;269:1532-1536.
21. Thompson D, Oster G. Use of terfenadine and contraindicated drugs. JAMA. 1996;275:1339-1341.
22. Kivistö KT, Neuvonen PJ, Klotz U. Inhibition of terfenadine metabolism: pharmacokinetic and pharmacodynamic consequences. Clin Pharmacokinet. 1994;27:1-5.
23. Bourdi M, Larrey D, Nataf J, et al. A new anti-liver endoplasmic reticulum antibody directed against human cytochrome P-450 IA2: a specific marker of dihydralazine-induced hepatitis. J Clin Invest. 1990;85:1967-1973.
24. Kalgutkar AS, Gardner I, Obach RS, et al. A comprehensive listing of bioactivation pathways of organic functional groups. Curr Drug Metab. 2005;6:161-225.
25. Guengerich FP. Principles of covalent binding of reactive metabolites and examples of activation of bis-electrophiles by conjugation. Arch Biochem Biophys. 2005;433:369-378.
26. Borzelleca JF. Profiles in toxicology. Paracelsus: herald of modern toxicology. Toxicol Sci. 2000;53:2-4.
27. Jollow DJ, Mitchell JR, Potter WZ, Davis DC, Gillette JR, Brodie BB. Acetaminophen-induced hepatic necrosis, II: role of covalent binding in vivo. J Pharmacol Exp Ther. 1973;187:195-202.
28. Evans DC, Watt AP, Nicoll-Griffith DA, Baillie TA. Drug-protein adducts: an industry perspective on minimizing the potential for drug bioactivation in drug discovery and development. Chem Res Toxicol. 2004;17:3-16.
29. Streeter AJ, Bjorge SM, Axworthy DB, Nelson SD, Baillie TA. The microsomal metabolism and site of covalent binding to protein of 3′-hydroxyacetanilide, a nonhepatotoxic positional isomer of acetaminophen. Drug Metab Dispos. 1984;12:565-576.
30. Roberts SA, Price VF, Jollow DJ. Acetaminophen structure-toxicity studies: in vivo covalent binding of a nonhepatotoxic analog, 3-hydroxyacetanilide. Toxicol Appl Pharmacol. 1990;105:195-208.
31. Qiu Y, Benet LZ, Burlingame AL. Identification of the hepatic protein targets of reactive metabolites of acetaminophen in vivo in mice using two-dimensional gel electrophoresis and mass spectrometry. J Biol Chem. 1998;273:17940-17953.
32. Park JYK, Shigenaga MK, Ames BN. Induction of cytochrome P4501A1 by 2,3,7,8-tetrachlorodibenzo-p-dioxin or indolo(3,2-b) carbazole is associated with oxidative DNA damage. Proc Natl Acad Sci USA. 1996;93:2322-2327.
33. Cederbaum AI, Wu D, Mari M, Bai J. CYP2E1-dependent toxicity and oxidative stress in HepG2 cells. Free Radic Biol Med. 2001;31:1539-1543.
34. Henderson CJ, Otto DM, Carrie D, et al. Inactivation of the hepatic cytochrome P450 system by conditional deletion of hepatic cytochrome P450 reductase. J Biol Chem. 2003;278:13480-13486.
35. Gu J, Weng Y, Zhang QY, et al. Liver-specific deletion of the NADPH-cytochrome P450 reductase gene: impact on plasma cholesterol homeostasis and the function and regulation of microsomal cytochrome P450 and heme oxygenase. J Biol Chem. 2003;278:25895-25901.
36. 1 oxidation products with lysine. Chem Res Toxicol. 2002;15:780-792.
37. 1exo-8,9-oxide and rearrangement of the dihydrodiol. J Am Chem Soc. 1996;118:8213-8220.
38. 1exo-8,9-epoxide with DNA: kinetic analysis of covalent binding and DNA-induced hydrolysis. Proc Natl Acad Sci USA. 1997; 94:6121-6125.
39. 1 dialdehyde by rat and human aldo-keto reductases. Chem Res Toxicol. 2001;14:727-737.
40. Stewart RD, Dodd HC, Gay HH, Erley DS. Experimental human exposure to trichloroethylene. Arch Environ Health. 1970;20:64-71.
41. Agency for Toxic Substances and Disease Registry, Centers for Disease Control and Prevention. Toxicological Profile for Trichloroethylene. Available at: http://www.atsdr.cdc.gov/toxprofiles/tp19.html. Accessed February 16, 2006.
42. Huff JE. New evidence on the old problems of trichloroethylene. 1971;40:25-33.
43. Lockey JE, Kelly CR, Cannon GW, Colby TV, Aldrich V, Livingston GK. Progressive systemic sclerosis associated with exposure to trichloroethylene. J Occup Med. 1987;29:493-496.
44. Kilburn KH. Is neurotoxicity associated with environmental trichloroethylene (TCE)? Arch Environ Health. 2002;57:113-120.
45. Miller RE, Guengerich FP. Oxidation of trichloroethylene by liver microsomal cytochrome P-450: evidence for chlorine migration in a transition state not involving trichloroethylene oxide. Biochemistry. 1982;21:1090-1097.
46. Cai H, Guengerich FP. Mechanism of aqueous decomposition of trichloroethylene oxide. J Am Chem Soc. 1999;121:11656-11663.
47. Yoshioka T, Krauser JA, Guengerich FP. Microsomal oxidation of tribromoethylene and reactions of tribromoethylene oxide. Chem Res Toxicol. 2002;15:1414-1420.
48. Cai H, Guengerich FP. Reaction of trichloroethylene oxide with proteins and DNA: instability of adducts and modulation of functions. Chem Res Toxicol. 2001;14:54-61.
49. Yoshioka T, Krauser JA, Guengerich FP. Tetrachloroethylene oxide: hydrolytic products and reactions with phosphate and lysine. Chem Res Toxicol. 2002;15:1096-1105.
50. Turesky RJ, Constable A, Richoz J, et al. Differences in activation of heterocyclic aromatic amines by rat and human liver microsomes and by rat and human cytochromes P450 1A2. Chem Res Toxicol. 1998;11:925-936.
51. Reitz RH, Mendrala A, Guengerich FP. In vitro metabolism of methylene chloride in human and animal tissues: use in physiologically based pharmacokinetic models. Toxicol Appl Pharmacol. 1989;97:230-246.
52. Kirman CR, Hays SM, Gargas ML, et al. Using physiologically based pharmacokinetic modeling to assess non-linearity in the dose-response relationship for methylene chloride carcinogenesis. Toxicologist. 1999;48:83.
53. Rish W, Kirman CR, Hays SM, et al. Developing a physiologically based pharmacokinetic model to describe methylene chloride kinetics at the subcellular level. Toxicologist. 1999;48:143.
54. Dorne JL, Walton K, Slob W, Renwick AG. Human variability in polymorphic CYP2D6 metabolism: is the kinetic default uncertainty factor adequate? Food Chem Toxicol. 2002;40:1633-1656.
55. Dorne JL, Walton K, Renwick AG. Human variability in CYP3A4 metabolism and CYP3A4-related uncertainty factors for risk assessment. Food Chem Toxicol. 2003;41:201-224.
56. Walgren JL, Mitchell MD, Thompson DC. Role of metabolism in drug-induced idiosyncratic hepatotoxicity. Crit Rev Toxicol. 2005;35:325-361.
57. Food and Drug Administration, Center for Drug Evaluation and Research. Draft: Guidance for industry: Safety testing of drug metabolites. Available at: http://www.fda.gov/cder/guidance/6366dft.htm. Accessed February 16, 2006.
58. Kupfer D, Bulger WH. Metabolic activation of pesticides with proestrogenic activity. Fed Proc. 1987;46:1864-1869.