Hepatic CYP2B6 is altered by genetic, physiologic, and environmental factors but plays little role in nicotine metabolism

Xenobiotica

Volumn 40, Issue 6, 2010, Pages 381-392

  Al Koudsi, N ^a   Tyndale, R F ^a  

^a UNIVERSITY OF TORONTO   (Canada)

Author keywords

Age; CYP2A6; CYP2B6; Gender; Nicotine; Pharmacogenetics

Indexed keywords

CYTOCHROME P450 2B6; DEXAMETHASONE; NICOTINE; PHENOBARBITAL;

ADOLESCENT; ADULT; AGE DISTRIBUTION; ARTICLE; CONTROLLED STUDY; ENVIRONMENTAL FACTOR; ENZYME ACTIVITY; ENZYME ANALYSIS; EXPOSURE; FEMALE; GENOTYPE; HUMAN; HUMAN TISSUE; LIVER LEVEL; LIVER MICROSOME; LIVER PARENCHYMA; MALE; MOLECULAR GENETICS; MUTATIONAL ANALYSIS; OXIDATION; PROTEIN EXPRESSION; RESTRICTION FRAGMENT LENGTH POLYMORPHISM; SEX DIFFERENCE; SINGLE NUCLEOTIDE POLYMORPHISM; XENOBIOTIC METABOLISM;

ADOLESCENT; ADULT; AGE FACTORS; ARYL HYDROCARBON HYDROXYLASES; FEMALE; GENOTYPE; HUMANS; LINEAR MODELS; LIVER; MALE; MIDDLE AGED; NICOTINE; OXIDATION-REDUCTION; OXIDOREDUCTASES, N-DEMETHYLATING; SEX FACTORS; YOUNG ADULT;

EID: 77952278911     PISSN: 00498254     EISSN: 13665928     Source Type: Journal    
DOI: 10.3109/00498251003713958     Document Type: Article

References (66)

1. Al Koudsi N, Hofmann EB, Assadzadeh A, Tyndale RF. (2010). Hepatic CYP2A6 levels and nicotine metabolism: impact of genetic, physiological, environmental, and epigenetic factors. Eur J Clin Pharmacol 66 (3) : 239-51.
2. Aoyama T, Yamano S, Guzelian PS, Gelboin HV, Gonzalez FJ. (1990). Five of 12 forms of vaccinia virus-expressed human hepatic cytochrome P450 metabolically activate aflatoxin B1. Proc Natl Acad Sci USA 87 (12) : 4790-3.
3. Benowitz NL. (2009). Pharmacology of nicotine: addiction, smokinginduced disease, and therapeutics. Annu Rev Pharmacol Toxicol 49: 57-71.
4. Benowitz NL, Jacob P, III. (1994). Metabolism of nicotine to cotinine studied by a dual stable isotope method. Clin Pharmacol Ther 56 (5) : 483-93.
5. Burger D, van der Heiden I, la Porte C, van der Ende M, Groeneveld P, Richter C, Koopmans P, Kroon F, Sprenger H, Lindemans J, Schenk P, Van Schaik R (2006). Interpatient variability in the pharmacokinetics of the HIV non-nucleoside reverse transcriptase inhibitor efavirenz: the effect of gender, race, and CYP2B6 polymorphism. Br J Clin Pharmacol 61 (2) : 148-54.
6. Campbell ME, Grant DM, Inaba T, Kalow W. (1987). Biotransformation of caffeine, paraxanthine, theophylline, and theobromine by polycyclic aromatic hydrocarbon-inducible cytochrome (s) P-450 in human liver microsomes. Drug Metab Dispos 15 (2) : 237-49.
7. Chang TK, Bandiera SM, Chen J. (2003). Constitutive androstane receptor and pregnane X receptor gene expression in human liver: interindividual variability and correlation with CYP2B6 mRNA levels. Drug Metab Dispos 31 (1) : 7-10.
8. Court MH, Duan SX, Hesse LM, Venkatakrishnan K, Greenblatt DJ. (2001). Cytochrome P-450 2B6 is responsible for interindividual variability of propofol hydroxylation by human liver microsomes. Anesthesiology 94 (1) : 110-19.
9. Croom EL, Stevens JC, Hines RN, Wallace AD, Hodgson E. (2009). Human hepatic CYP2B6 developmental expression: the impact of age and genotype. Biochem Pharmacol 78 (2) : 184-90.
10. Csajka C, Marzolini C, Fattinger K, Decosterd LA, Fellay J, Telenti A, Biollaz J, Buclin T. (2003). Population pharmacokinetics and effects of efavirenz in patients with human immunodeficiency virus infection. Clin Pharmacol Ther 73 (1) : 20-30.
11. Desta Z, Saussele T, Ward B, Blievernicht J, Li L, Klein K, Flockhart DA, Zanger UM. (2007). Impact of CYP2B6 polymorphism on hepatic efavirenz metabolism in vitro. Pharmacogenomics 8 (6) : 547-58.
12. Dhir RN, Dworakowski W, Thangavel C, Shapiro BH. (2006). Sexually dimorphic regulation of hepatic isoforms of human cytochrome p450 by growth hormone. J Pharmacol Exp Ther 316 (1) : 87-94.
13. Donato MT, Viitala P, Rodriguez-Antona C, Lindfors A, Castell JV, Raunio H, Gomez-Lechon MJ, Pelkonen O. (2000). CYP2A5/CYP2A6 expression in mouse and human hepatocytes treated with various in vivo inducers. Drug Metab Dispos 28 (11) : 1321-6.
14. Faucette SR, Hawke RL, Lecluyse EL, Shord SS, Yan B, Laethem RM, Lindley CM. (2000). Validation of bupropion hydroxylation as a selective marker of human cytochrome P450 2B6 catalytic activity. Drug Metab Dispos 28 (10) : 1222-30.
15. Faucette SR, Wang H, Hamilton GA, Jolley SL, Gilbert D, Lindley C, Yan B, Negishi M, LeCluyse EL. (2004). Regulation of CYP2B6 in primary human hepatocytes by prototypical inducers. Drug Metab Dispos 32 (3) : 348-58.
16. Forrester LM, Henderson CJ, Glancey MJ, Back DJ, Park BK, Ball SE, Kitteringham NR, McLaren AW, Miles JS, Skett P, Wolf CR. (1992). Relative expression of cytochrome P450 isoenzymes in human liver and association with the metabolism of drugs and xenobiotics. Biochem J 281 (Pt 2) : 359-68.
17. *26. Clin Infect Dis 45 (9) : 1230-7.
18. Gervot L, Rochat B, Gautier JC, Bohnenstengel F, Kroemer H, de Berardinis V, Martin H, Beaune P, de Waziers I. (1999). Human CYP2B6: expression, inducibility and catalytic activities. Pharmacogenetics 9 (3) : 295-306.
19. Haberl M, Anwald B, Klein K, Weil R, Fuss C, Gepdiremen A, Zanger UM, Meyer UA, Wojnowski L. (2005). Tree haplotypes associated with CYP2A6 phenotypes in Caucasians. Pharmacogenet Genomics 15 (9) : 609-24.
20. Hanna IH, Reed JR, Guengerich FP, Hollenberg PF. (2000). Expression of human cytochrome P450 2B6 in Escherichia coli: characterization of catalytic activity and expression levels in human liver. Arch Biochem Biophys 376 (1) : 206-16.
21. Hesse LM, He P, Krishnaswamy S, Hao Q, Hogan K, von Moltke LL, Greenblatt DJ, Court MH. (2004). Pharmacogenetic determinants of interindividual variability in bupropion hydroxylation by cytochrome P450 2B6 in human liver microsomes. Pharmacogenetics 14 (4) : 225-38.
22. Ho MK, Tyndale RF. (2007). Overview of the pharmacogenomics of cigarette smoking. Pharmacogenomics J 7 (2) : 81-98.
23. Hoffman SM, Nelson DR, Keeney DS. (2001). Organization, structure and evolution of the CYP2 gene cluster on human chromosome 19. Pharmacogenetics 11 (8) : 687-98.
24. *6, is responsible for decreased expression and activity of CYP2B6 in liver. J Pharmacol Exp Ther 325 (1) : 284-92.
25. Hukkanen J, Jacob P, III, Benowitz NL. (2005). Metabolism and disposition kinetics of nicotine. Pharmacol Rev 57 (1) : 79-115.
26. Jaffe CA, Turgeon DK, Lown K, Demott-Friberg R, Watkins PB. (2002). Growth hormone secretion pattern is an independent regulator of growth hormone actions in humans. Am J Physiol Endocrinol Metab 283 (5) : E1008-15.
27. Jinno H, Tanaka-Kagawa T, Ohno A, Makino Y, Matsushima E, Hanioka N, Ando M. (2003). Functional characterization of cytochrome P450 2B6 allelic variants. Drug Metab Dispos 31 (4) : 398-403.
28. Kreth K, Kovar K, Schwab M, Zanger UM. (2000). Identification of the human cytochromes P450 involved in the oxidative metabolism of 'Ecstasy'-related designer drugs. Biochem Pharmacol 59 (12) : 1563-71.
29. Lamba V, Lamba J, Yasuda K, Strom S, Davila J, Hancock ML, Fackenthal JD, Rogan PK, Ring B, Wrighton SA, Schuetz EG. (2003). Hepatic CYP2B6 expression: gender and ethnic differences and relationship to CYP2B6 genotype and CAR (constitutive androstane receptor) expression. J Pharmacol Exp Ther 307 (3) : 906-22.
30. Lang T, Klein K, Fischer J, Nussler AK, Neuhaus P, Hofmann U, Eichelbaum M, Schwab M, Zanger UM. (2001). Extensive genetic polymorphism in the human CYP2B6 gene with impact on expression and function in human liver. Pharmacogenetics 11 (5) : 399-415.
31. Lee AM, Jepson C, Hoffmann E, Epstein L, Hawk LW, Lerman C, Tyndale RF. (2007a). CYP2B6 genotype alters abstinence rates in a bupropion smoking cessation trial. Biol Psychiatry 62 (6) : 635-41.
32. Lee AM, Jepson C, Shields PG, Benowitz N, Lerman C, Tyndale RF. (2007b). CYP2B6 genotype does not alter nicotine metabolism, plasma levels, or abstinence with nicotine replacement therapy. Cancer Epidemiol Biomarkers Prev 16 (6) : 1312-4.
33. Liddle C, Goodwin BJ, George J, Tapner M, Farrell GC. (1998). Separate and interactive regulation of cytochrome P450 3A4 by triiodothyronine, dexamethasone, and growth hormone in cultured hepatocytes. J Clin Endocrinol Metab 83 (7) : 2411-16.
34. Madan A, Graham RA, Carroll KM, Mudra DR, Burton LA, Krueger LA, Downey AD, Forster J, Ribadeneira MD, Gan LS, LeCluyse EL, Zech K, Robertson P Jr, Koch P, Antonian L, Wagner G, Yu L, Parkinson A. (2003). Effects of prototypical microsomal enzyme inducers on cytochrome P450 expression in cultured human hepatocytes. Drug Metab Dispos 31 (4) : 421-31.
35. Marzolini C, Telenti A, Decosterd LA, Greub G, Biollaz J, Buclin T. (2001). Efavirenz plasma levels can predict treatment failure and central nervous system side-effects in HIV-1-infected patients. AIDS 15 (1) : 71-5. (Pubitemid 32055781)
36. Maurice M, Emiliani S, Dalet-Beluche I, Derancourt J, Lange R. (1991). Isolation and characterization of a cytochrome P450 of the IIA subfamily from human liver microsomes. Eur J Biochem 200 (2) : 511-17.
37. Meier PJ, Mueller HK, Dick B, Meyer UA. (1983). Hepatic monooxygenase activities in subjects with a genetic defect in drug oxidation. Gastroenterology 85 (3) : 682-92.
38. Messina ES, Tyndale RF, Sellers EM. (1997). A major role for CYP2A6 in nicotine C-oxidation by human liver microsomes. J Pharmacol Exp Ther 282 (3) : 1608-14.
39. Miles JS, Bickmore W, Brook JD, McLaren AW, Meehan R, Wolf CR. (1989). Close linkage of the human cytochrome P450IIA and P450IIB gene subfamilies: implications for the assignment of substrate specificity. Nucleic Acids Res 17 (8) : 2907-17.
40. Mimura M, Baba T, Yamazaki H, Ohmori S, Inui Y, Gonzalez FJ, Guengerich FP, Shimada T. (1993). Characterization of cytochrome P-450 2B6 in human liver microsomes. Drug Metab Dispos 21 (6) : 1048-56.
41. Mo SL, Liu YH, Duan W, Wei MQ, Kanwar JR, Zhou SF. (2009). Substrate Specificity, Regulation, and Polymorphism of Human Cytochrome P450 2B6. Curr Drug Metab.
42. Murayama N, Shimada M, Yamazoe Y, Kato R. (1991). Difference in the susceptibility of two phenobarbital-inducible forms, P450IIB1 and P450IIB2, to thyroid hormone-and growth hormone-induced suppression in rat liver: phenobarbital-inducible P450IIB2 suppression by thyroid hormone acting directly, but not through the pituitary system. Mol Pharmacol 39 (6) : 811-17.
43. Nakajima M, Yamamoto T, Nunoya K, Yokoi T, Nagashima K, Inoue K, Funae Y, Shimada N, Kamataki T, Kuroiwa Y. (1996a). Characterization of CYP2A6 involved in 3'-hydroxylation of cotinine in human liver microsomes. J Pharmacol Exp Ther 277 (2) : 1010-15.
44. Nakajima M, Yamamoto T, Nunoya K, Yokoi T, Nagashima K, Inoue K, Funae Y, Shimada N, Kamataki T, Kuroiwa Y. (1996b). Role of human cytochrome P4502A6 in C-oxidation of nicotine. Drug Metab Dispos 24 (11) : 1212-17.
45. Nelson DR, Koymans L, Kamataki T, Stegeman JJ, Feyereisen R, Waterman MR, Gotoh O, Coon MJ, Estabrook RW, Gunsalus IC, Nebert DW. (1996). P450 superfamily: update on new sequences, gene mapping, accession numbers and nomenclature. Pharmacogenetics 6 (1) : 1-42.
46. Parkinson A, Mudra DR, Johnson C, Dwyer A, Carroll KM. (2004). The effects of gender, age, ethnicity, and liver cirrhosis on cytochrome P450 enzyme activity in human liver microsomes and inducibility in cultured human hepatocytes. Toxicol Appl Pharmacol 199 (3) : 193-209.
47. Pelkonen O, Rautio A, Raunio H, Pasanen M. (2000). CYP2A6: a human coumarin 7-hydroxylase. Toxicology 144(1-3):139-47.
48. Ring HZ, Valdes AM, Nishita DM, Prasad S, Jacob P, III, Tyndale R F, Swan GE, Benowitz NL. (2007). Gene-gene interactions between CYP2B6 and CYP2A6 in nicotine metabolism. Pharmacogenet Genomics 17 (12) : 1007-15.
49. Rotger M, Tegude H, Colombo S, Cavassini M, Furrer H, Decosterd L, Blievernicht J, Saussele T, Gunthard HF, Schwab M, Eichelbaum M, Telenti A, Zanger UM. (2007). Predictive value of known and novel alleles of CYP2B6 for efavirenz plasma concentrations in HIV-infected individuals. Clin Pharmacol Ther 81 (4) : 557-66.
50. Roy P, Yu LJ, Crespi CL, Waxman DJ. (1999). Development of a substrate-activity based approach to identify the major human liver P-450 catalysts of cyclophosphamide and ifosfamide activation based on cDNA-expressed activities and liver microsomal P-450 profiles. Drug Metab Dispos 27 (6) : 655-66.
51. Shimada T, Yamazaki H, Mimura M, Inui Y, Guengerich FP. (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 (1) : 414-23.
52. Staszewski S, Morales-Ramirez J, Tashima KT, Rachlis A, Skiest D, Stanford J, Stryker R, Johnson P, Labriola DF, Farina D, Manion DJ, Ruiz NM. (1999). Efavirenz plus zidovudine and lamivudine, efavirenz plus indinavir, and indinavir plus zidovudine and lamivudine in the treatment of HIV-1 infection in adults. Study 006 Team. N Engl J Med 341 (25) : 1865-73.
53. Stresser DM, Kupfer D. (1999). Monospecific antipeptide antibody to cytochrome P-450 2B6. Drug Metab Dispos 27 (4) : 517-25.
54. Strom SC, Pisarov LA, Dorko K, Tompson MT, Schuetz JD, Schuetz EG. (1996). Use of human hepatocytes to study P450 gene induction. Methods Enzymol 272: 388-401.
55. Sueyoshi T, Kawamoto T, Zelko I, Honkakoski P, Negishi M. (1999). The repressed nuclear receptor CAR responds to phenobarbital in activating the human CYP2B6 gene. J Biol Chem 274 (10) : 6043-6.
56. Tateishi T, Nakura H, Asoh M, Watanabe M, Tanaka M, Kumai T, Takashima S, Imaoka S, Funae Y, Yabusaki Y, Kamataki T, Kobayashi S. (1997). A comparison of hepatic cytochrome P450 protein expression between infancy and postinfancy. Life Sci 61 (26) : 2567-74. (Pubitemid 28035581)
57. Telenti A, Zanger UM. (2008). Pharmacogenetics of anti-HIV drugs. Annu Rev Pharmacol Toxicol 48: 227-56.
58. Turpeinen M, Raunio H, Pelkonen O. (2006). The functional role of CYP2B6 in human drug metabolism: substrates and inhibitors in vitro, in vivo and in silico. Curr Drug Metab 7 (7) : 705-14.
59. Wang J, Sonnerborg A, Rane A, Josephson F, Lundgren S, Stahle L, Ingelman-Sundberg M. (2006). Identification of a novel specific CYP2B6 allele in Africans causing impaired metabolism of the HIV drug efavirenz. Pharmacogenet Genomics 16 (3) : 191-8.
60. Ward BA, Gorski JC, Jones DR, Hall SD, Flockhart DA, Desta Z. (2003). The cytochrome P450 2B6 (CYP2B6) is the main catalyst of efavirenz primary and secondary metabolism: implication for HIV/AIDS therapy and utility of efavirenz as a substrate marker of CYP2B6 catalytic activity. J Pharmacol Exp Ther 306 (1) : 287-300.
61. Waxman DJ, O'Connor C. (2006). Growth hormone regulation of sex-dependent liver gene expression. Mol Endocrinol 20 (11) : 2613-29.
62. Wortham M, Czerwinski M, He L, Parkinson A, Wan YJ. (2007). Expression of constitutive androstane receptor, hepatic nuclear factor 4 alpha, and P450 oxidoreductase genes determines interindividual variability in basal expression and activity of a broad scope of xenobiotic metabolism genes in the human liver. Drug Metab Dispos 35 (9) : 1700-10.
63. Yamazaki H, Inoue K, Hashimoto M, Shimada T. (1999). Roles of CYP2A6 and CYP2B6 in nicotine C-oxidation by human liver microsomes. Arch Toxicol 73 (2) : 65-70.
64. Yanagihara Y, Kariya S, Ohtani M, Uchino K, Aoyama T, Yamamura Y, Iga T. (2001). Involvement of CYP2B6 in n-demethylation of ketamine in human liver microsomes. Drug Metab Dispos 29 (6) : 887-90.
65. Zanger UM, Klein K, Saussele T, Blievernicht J, Hofmann MH, Schwab M. (2007). Polymorphic CYP2B6: molecular mechanisms and emerging clinical significance. Pharmacogenomics 8 (7) : 743-59.
66. Zukunft J, Lang T, Richter T, Hirsch-Ernst KI, Nussler AK, Klein K, Schwab M, Eichelbaum M, Zanger UM. (2005). A natural CYP2B6 TATA box polymorphism (-82T → C) leading to enhanced transcription and relocation of the transcriptional start site. Mol Pharmacol 67 (5) : 1772-82.