Effects of genetic variants of human P450 oxidoreductase on catalysis by CYP2D6 in vitro

Pharmacogenetics and Genomics

Volumn 20, Issue 11, 2010, Pages 677-686

  Sandee, Duanpen ^a   Morrissey, Kari ^b   Agrawal, Vishal ^a   Tam, Harrison K ^c   Kramer, Melissa A ^c   Tracy, Timothy S ^c   Giacomini, Kathleen M ^b   Miller, Walter L ^a  

^a UNIVERSITY OF CALIFORNIA   (United States)

^b San Francisco   (United States)

^c UNIVERSITY OF MINNESOTA   (United States)

Author keywords

bufuralol; cytochrome P450; dextromethorphan; drug metabolism; electron transfer; enzyme kinetics; pharmacogenetics

Indexed keywords

7 (ETHOXYMETHOXY) 2 OXO 2H 1 BENZOPYRAN 3 CARBONITRILE; BENZOPYRAN DERIVATIVE; BUFURALOL; CYTOCHROME P450 2D6; CYTOCHROME P450 REDUCTASE; DEXTROMETHORPHAN; DEXTRORPHAN; UNCLASSIFIED DRUG;

ARTICLE; BACTERIAL MEMBRANE; CATALYSIS; DRUG ACTIVITY; DRUG METABOLISM; ENZYME ACTIVITY; ENZYME METABOLISM; GENE FREQUENCY; GENETIC POLYMORPHISM; GENETIC VARIABILITY; IN VITRO STUDY; MUTATION; PRIORITY JOURNAL; PROTEIN EXPRESSION; STEROIDOGENESIS;

BENZOPYRANS; CATALYSIS; CYTOCHROME P-450 CYP2D6; DEXTROMETHORPHAN; ETHANOLAMINES; GENETIC VARIATION; HUMANS; METABOLIC DETOXICATION, DRUG; MUTATION; NADPH-FERRIHEMOPROTEIN REDUCTASE; OXIDOREDUCTASES; POLYMORPHISM, GENETIC;

BACTERIA (MICROORGANISMS); ESCHERICHIA COLI;

EID: 77958581296     PISSN: 17446872     EISSN: 17446880     Source Type: Journal    
DOI: 10.1097/FPC.0b013e32833f4f9b     Document Type: Article

References (46)

1. Nelson DR. Comparison of P450s from human and fugu: 420 million years of vertebrate P450 evolution. Arch Biochem Biophys 2003; 409:18-24.
2. Guengerich FP. Cytochrome P450: what have we learned and what are the future issues? Drug Metab Rev 2004; 36:159-197.
3. Miller WL. Minireview: regulation of steroidogenesis by electron transfer. Endocrinology 2005; 146:2544-2550.
4. Scott RR, Gomes LG, Huang N, Van Vliet G, Miller WL. Apparent manifesting heterozygosity in P450 oxidoreductase deficiency and its effect on coexisting 21-hydroxylase deficiency. J Clin Endocrinol Metab 2007; 92:2318-2322.
5. Wang M, Roberts DL, Paschke R, Shea TM, Masters BS, Kim JJ. Three-dimensional structure of NADPH-cytochrome P450 reductase: prototype for FMN-and FAD-containing enzymes. Proc Natl Acad Sci \USA 1997; 94:8411-8416.
6. Hubbard PA, Shen AL, Paschke R, Kasper CB, Kim JJ. NADPH-cytochrome P450 oxidoreductase. Structural basis for hydride and electron transfer. J Biol Chem 2001; 276:29163-29170.
7. Ellis J, Gutierrez A, Barsukov IL, Huang WC, Grossmann JG, Roberts GC. Domain motion in cytochrome P450 reductase: conformational equilibria revealed by NMR and small-angle X-ray scattering. J Biol Chem 2009; 284:36628-36637.
8. Shen AL, O'Leary KA, Kasper CB. Association of multiple developmental defects and embryonic lethality with loss of microsomal NADPH-cytochrome P450 oxidoreductase. J Biol Chem 2002; 277:6536-6541.
9. Otto DM, Henderson CJ, Carrie D, Davey M, Gundersen TE, Blomhoff R, et al. Identification of novel roles of the cytochrome P450 system in early embryogenesis: effects on vasculogenesis and retinoic acid homeostasis. Mol Cell Biol 2003; 23:6103-6116.
10. Henderson CJ, Otto DM, Carrie D, Magnuson MA, McLaren AW, Rosewell I, et al. Inactivation of the hepatic cytochrome P450 system by conditional deletion of hepatic cytochrome P450 reductase. J Biol Chem 2003; 278:13480-13486.
11. Gu J, Weng Y, Zhang QY, Cui H, Behr M, Wu L, 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.
12. Finn RD, McLaren AW, Carrie D, Henderson CJ, Wolf CR. Conditional deletion of cytochrome P450 oxidoreductase in the liver and gastrointestinal tract: a new model for studying the functions of the P450 system. J Pharmacol Exp Ther 2007; 322:40-47.
13. Fluck CE, Tajima T, Pandey AV, Arlt W, Okuhara K, Verge CF, et al. Mutant P450 oxidoreductase causes disordered steroidogenesis with and without Antley-Bixler syndrome. Nat Genet 2004; 36:228-230.
14. Antley R, Bixler D. Trapezoidocephaly, midfacial hypoplasia and cartilage abnormalities with multiple synostoses and skeletal fractures. Birth Defects Orig Artic Ser 1975; 11:397-401.
15. Huang N, Pandey AV, Agrawal V, Reardon W, Lapunzina PD, Mowat D, et al. Diversity and function of mutations in P450 oxidoreductase in patients with Antley-Bixler syndrome and disordered steroidogenesis. Am J Hum Genet 2005; 76:729-749.
16. Giacomini KM, Brett CM, Altman RB, Benowitz NL, Dolan ME, Flockhart DA, et al. The pharmacogenetics research network: from SNP discovery to clinical drug response. Clin Pharmacol Ther 2007; 81:328-345.
17. Bertz RJ, Granneman GR. Use of in vitro and in vivo data to estimate the likelihood of metabolic pharmacokinetic interactions. Clin Pharmacokinet 1997; 32:210-258.
18. Evans WE, Relling MV. Pharmacogenomics: translating functional genomics into rational therapeutics. Science 1999; 286:487-491.
19. Sachse C, Brockmoller J, Bauer S, Roots I. Cytochrome P450 2D6 variants in a Caucasian population: allele frequencies and phenotypic consequences. Am J Hum Genet 1997; 60:284-295.
20. Mahgoub A, Idle JR, Dring LG, Lancaster R, Smith RL. Polymorphic hydroxylation of Debrisoquine in man. Lancet 1977; 2:584-586.
21. Dalen P, Dahl ML, Eichelbaum M, Bertilsson L, Wilkinson GR. Disposition of debrisoquine in Caucasians with different CYP2D6-genotypes including those with multiple genes. Pharmacogenetics 1999; 9:697-706.
22. Dorado P, Berecz R, Caceres MC, Gonzalez I, Cobaleda J, Llerena A. Determination of debrisoquine and 4-hydroxydebrisoquine by high-performance liquid chromatography: application to the evaluation of CYP2D6 genotype and debrisoquine metabolic ratio relationship. Clin Chem Lab Med 2005; 43:275-279.
23. Huang N, Agrawal V, Giacomini KM, Miller WL. Genetics of P450 oxidoreductase: sequence variation in 842 individuals of four ethnicities and activities of 15 missense mutations. Proc Natl Acad Sci \USA 2008; 105:1733-1738.
24. Sim SC, Miller WL, Zhong XB, Arlt W, Ogata T, Ding X, et al. Nomenclature for alleles of the cytochrome P450 oxidoreductase gene. Pharmacogenet Genomics 2009; 19:565-566.
25. Gomes LG, Huang N, Agrawal V, Mendonca BB, Bachega TA, Miller WL. The common P450 oxidoreductase variant A503V is not a modifier gene for 21-hydroxylase deficiency. J Clin Endocrinol Metab 2008; 93:2913-2916.
26. Agrawal V, Huang N, Miller WL. Pharmacogenetics of P450 oxidoreductase: effect of sequence variants on activities of CYP1A2 and CYP2C19. Pharmacogenet Genomics 2008; 18:569-576.
27. Agrawal V, Choi JH, Giacomini KM, Miller WL. Substrate-specific modulation of CYP3A4 activity by genetic variants of cytochrome P450 oxidoreductase (POR). Pharmacogenet Genomics 2010. doi: 10.1097/ FPC.0b013e328330cb5
28. Pandey AV, Kempna P, Hofer G, Mullis PE, Flück CE. Modulation of human CYP19A1 activity by mutant NADPH P450 oxidoreductase. Mol Endocrinol 2007; 21:2579-2595.
29. Barnes HJ, Arlotto MP, Waterman MR. Expression and enzymatic activity of recombinant cytochrome P450 17a-hydroxylase in Escherichia coli. Proc Natl Acad Sci \USA 1991; 88:5597-5601.
30. Halkier BA, Nielsen HL, Koch B, Moller BL. Purification and characterization of recombinant cytochrome P450TYR expressed at high levels in Escherichia coli. Arch Biochem Biophys 1995; 322:369-377.
31. Omura T, Sato R. The carbon monoxide-binding pigment of liver microsomes. I. Evidence for its hemoprotein nature. J Biol Chem 1964; 239:2370-2378.
32. Marks BD, Smith RW, Braun HA, Goossens TA, Christenson M, Ozers MS, et al. A high throughput screening assay to screen for CYP2E1 metabolism and inhibition using a fluorogenic vivid P450 substrate. Assay Drug Dev Technol 2002; 1:73-81.
33. Backes WL, Kelley RW. Organization of multiple cytochrome P450s with NADPH-cytochrome P450 reductase in membranes. Pharmacol Ther 2003; 98:221-233.
34. Deeni YY, Paine MJ, Ayrton AD, Clarke SE, Chenery R, Wolf CR. Expression, purification, and biochemical characterization of a human cytochrome P450 CYP2D6-NADPH cytochrome P450 reductase fusion protein. Arch Biochem Biophys 2001; 396:16-24.
35. Yu A, Kneller BM, Rettie AE, Haining RL. Expression, purification, biochemical characterization, and comparative function of human cytochrome P450 2D6.1, 2D6.2, 2D6.10, and 2D6.17 allelic isoforms. J Pharmacol Exp Ther 2002; 303:1291-1300.
36. 0-hydroxymethyl-a-pyrrolidinohexanophenone in fission yeast heterologously expressing human cytochrome P450 2D6-a versatile alternative to multistep chemical synthesis. J Anal Toxicol 2009; 33:190-197.
37. Fukami M, Horikawa R, Nagai T, Tanaka T, Naiki Y, Sato N, et al. Cytochrome P450 oxidoreductase gene mutations and Antley-Bixler syndrome with abnormal genitalia and/or impaired steroidogenesis: molecular and clinical studies in 10 patients. J Clin Endocrinol Metab 2005; 90:414-426.
38. Dierks EA, Davis SC, Ortiz de Montellano PR. Glu-320 and Asp-323 are determinants of the CYP4A1 hydroxylation regiospecificity and resistance to inactivation by 1-aminobenzotriazole. Biochemistry 1998; 37:1839-1847.
39. Nicolo C, Flück CE, Mullis PE, Pandey AV. Restoration of mutant cytochrome P450 reductase activity by external flavin. Mol Cell Endocrinol 2010; 321:245-252.
40. Hinkson JW. Azotobacter free-radical flavoprotein. Preparation and properties of the apoprotein. Biochemistry 1968; 7:2666-2672.
41. Hirth J, Watkins PB, Strawderman M, Schott A, Bruno R, Baker LH. The effect of an individual's cytochrome CYP3A4 activity on docetaxel clearance. Clin Cancer Res 2000; 6:1255-1258.
42. Mizutani T. PM frequencies of major CYPs in Asians and Caucasians. Drug Metab Rev 2003; 35:99-106.
43. Shuldiner AR, O'Connell JR, Bliden KP, Gandhi A, Ryan K, Horenstein RB, et al. Association of cytochrome P450 2C19 genotype with the antiplatelet effect and clinical efficacy of clopidogrel therapy. JAMA 2009; 302:849-857.
44. Dhir V, Ivison HE, Krone N, Shackleton CH, Doherty AJ, Stewart PM, et al. Differential inhibition of CYP17A1 and CYP21A2 activities by the P450 oxidoreductase mutant A287P. Mol Endocrinol 2007; 21:1958-1968.
45. Fluck CE, Mullis PE, Pandey AV. Modeling of human P450 oxidoreductase structure by in-silico mutagenesis and MD simulation. Mol Cell Endocrinol 2009; 313:17-22.
46. Evans WE, McLeod HL. Pharmacogenomics-drug disposition, drug targets, and side effects. N Engl J Med 2003; 348:538-549.