Orphans in the human cytochrome P450 superfamily: Approaches to discovering functions and relevance in pharmacology

Pharmacological Reviews

Volumn 63, Issue 3, 2011, Pages 684-699

  Peter Guengerich, F ^a   Cheng, Qian ^a  

^a VANDERBILT UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CARCINOGEN; CYTOCHROME P450; CYTOCHROME P450 20A1; CYTOCHROME P450 27C1; CYTOCHROME P450 2A7; CYTOCHROME P450 2S1; CYTOCHROME P450 2U1; CYTOCHROME P450 2W1; CYTOCHROME P450 3A43; CYTOCHROME P450 4A22; CYTOCHROME P450 4F11; CYTOCHROME P450 4F22; CYTOCHROME P450 4V2; CYTOCHROME P450 4X1; CYTOCHROME P450 4Z1; ESCHERICHIA COLI PROTEIN; FATTY ACID; SACCHAROMYCES CEREVISIAE PROTEIN; SCHIZOSACCHAROMYCES POMBE PROTEIN; UNCLASSIFIED DRUG; VITAMIN D; XENOBIOTIC AGENT;

ARTICLE; BINDING KINETICS; BIOINFORMATICS; BIOTRANSFORMATION; CATALYSIS; ENZYME ACTIVE SITE; ENZYME METABOLISM; ENZYME SUBSTRATE; ESCHERICHIA COLI; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; HUMAN; HYDROXYLATION; LIQUID CHROMATOGRAPHY; METABOLOMICS; MOLECULAR BIOLOGY; NONHUMAN; PRIORITY JOURNAL; PROTEIN ANALYSIS; PROTEIN FUNCTION; SACCHAROMYCES CEREVISIAE; SCHIZOSACCHAROMYCES POMBE; SINGLE NUCLEOTIDE POLYMORPHISM; TANDEM MASS SPECTROMETRY;

ANIMALS; BIOCHEMISTRY; CYTOCHROME P-450 ENZYME SYSTEM; HUMANS; ISOENZYMES; ORGAN SPECIFICITY; PHARMACOLOGY; SUBSTRATE SPECIFICITY;

EID: 79960657926     PISSN: 00316997     EISSN: 15210081     Source Type: Journal    
DOI: 10.1124/pr.110.003525     Document Type: Article

References (105)

1. Agarwal V, Kommaddi RP, Valli K, Ryder D, Hyde TM, Kleinman JE, Strobel HW, and Ravindranath V (2008) Drug metabolism in human brain: high levels of cytochrome P4503A43 in brain and metabolism of anti-anxiety drug alprazolam to its active metabolite. PLos One 3: e2337.
2. Bollard ME, Stanley EG, Lindon JC, Nicholson JK, and Holmes E (2005) NMR-based metabonomic approaches for evaluating physiological influences on biofluid composition. NMR Biomed 18: 143-162.
3. Bui PH and Hankinson O (2009) Functional characterization of human cytochrome P450 2S1 using a synthetic gene-expressed protein in Escherichia coli. Mol Pharmacol 76: 1031-1043.
4. Bui PH, Hsu EL, and Hankinson O (2009) Fatty acid hydroperoxides support cytochrome P450 2S1-mediated bioactivation of benzo[a]pyrene-7,8-dihydrodiol. Mol Pharmacol 76: 1044-1052.
5. Bui P, Imaizumi S, Beedanagari SR, Reddy ST, and Hankinson O (2010) Human CYP2S1 metabolizes cyclooxygenase-and lipoxygenase-derived eicosanoids. Drug Metab Dispos 39: 180-190.
6. Bylund J, Zhang C, and Harder DR (2002) Identification of a novel cytochrome P450, CYP4X1, with unique localization specific to the brain. Biochem Biophys Res Commun 296: 677-684.
7. Cheng Q, Lamb DC, Kelly SL, Lei L, and Guengerich FP (2010) Cyclization of a cellular dipentaenone by Streptomyces coelicolor cytochrome P450 154A1 without oxidation/reduction. J Am Chem Soc 132: 15173-15175.
8. Chuang SS, Helvig C, Taimi M, Ramshaw HA, Collop AH, Amad M, White JA, Petkovich M, Jones G, and Korczak B (2004) CYP2U1, a novel human thymus-and brain-specific cytochrome P450, catalyzes ω-and (ω-1)-hydroxylation of fatty acids. J Biol Chem 279: 6305-6314.
9. Cui X, Nelson DR, and Strobel HW (2000) A novel human cytochrome P450 4F isoform (CYP4F11): cDNA cloning, expression, and genomic structural characterization. Genomics 68: 161-166.
10. Dhar M, Sepkovic DW, Hirani V, Magnusson RP, and Lasker JM (2008) Omega oxidation of 3-hydroxy fatty acids by the human CYP4F gene subfamily enzyme CYP4F11. J Lipid Res 49: 612-624.
11. Ding S, Lake BG, Friedberg T, and Wolf CR (1995) Expression and alternative splicing of the cytochrome P-450 CYP2A7. Biochem J 306: 161-166.
12. Domanski TL, Finta C, Halpert JR, and Zaphiropoulos PG (2001) cDNA cloning and initial characterization of CYP3A43, a novel human cytochrome P450. Mol Pharmacol 59: 386-392.
13. Downie D, McFadyen MC, Rooney PH, Cruickshank ME, Parkin DE, Miller ID, Telfer C, Melvin WT, and Murray GI (2005) Profiling cytochrome P450 expression in ovarian cancer: identification of prognostic markers. Clin Cancer Res 11: 7369-7375.
14. Du L, Neis MM, Ladd PA, Lanza DL, Yost GS, and Keeney DS (2006) Effects of the differentiated keratinocyte phenotype on expression levels of CYP1-4 family genes in human skin cells. Toxicol Appl Pharmacol 213: 135-144.
15. Dunayevskiy YM, Vouros P, Wintner EA, Shipps GW, Carell T, and Rebek J, Jr. (1996) Application of capillary electrophoresis-electrospray ionization mass spectrometry in the determination of molecular diversity. Proc Natl Acad Sci USA 93: 6152-6157.
16. Duran AL, Yang J, Wang L, and Sumner LW (2003) Metabolomics spectral formatting, alignment and conversion tools (MSFACTs). Bioinformatics 19: 2283-2293.
17. Gerlt JA and Babbitt PC (2001) Divergent evolution of enzymatic function: mechanistically diverse superfamilies and functionally distinct suprafamilies. Annu Rev Biochem 70: 209-246.
18. Godoy W, Albano RM, Moraes EG, Pinho PR, Nunes RA, Saito EH, Higa C, Filho IM, Kruel CD, Schirmer CC, et al. (2002) CYP2A6/2A7 and CYP2E1 expression in human oesophageal mucosa: regional and inter-individual variation in expression and relevance to nitrosamine metabolism. Carcinogenesis 23: 611-616.
19. Gomez A, Nekvindova J, Travica S, Lee MY, Johansson I, Edler D, Mkrtchian S, and Ingelman-Sundberg M (2010) Colorectal cancer-specific cytochrome P450 2W1: intracellular localization, glycosylation, and catalytic activity. Mol Pharmacol 78: 1004-1011.
20. Gonzalez FJ and Nebert DW (1990) Evolution of the P450 gene superfamily: animalplant 'warfare', molecular drive and human genetic differences in drug oxidation. Trends Genet 6: 182-186.
21. Gonzalez FJ and Yu AM (2006) Cytochrome P450 and xenobiotic receptor humanized mice. Annu Rev Pharmacol Toxicol 46: 41-64.
22. Gu J, Weng Y, Zhang QY, Cui H, Behr M, Wu L, Yang W, Zhang L, and Ding X (2003) 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 278: 25895-25901.
23. Guengerich FP (1999) Human cytochrome P-450 3A4: regulation and role in drug metabolism. Annu Rev Pharmacol Toxicol 39: 1-17.
24. Guengerich FP (2001) Common and uncommon cytochrome P450 reactions related to metabolism and chemical toxicity. Chem Res Toxicol 14: 611-650.
25. Guengerich FP (2005) Human cytochrome P450 enzymes, in Cytochrome P450: Structure Mechanism, and Biochemistry, 3rd ed (Ortiz de Montellano PR ed) pp 377-530, Kluwer Academic/Plenum Publishers, New York.
26. Guengerich FP, Ballou DP, and Coon MJ (1976) Spectral intermediates in the reaction of oxygen with purified liver microsomal cytochrome P-450. Biochem Biophys Res Commun 70: 951-956.
27. Guengerich FP and Isin EM (2011) Unusual metabolic reactions and pathways, in Handbook of Metabolic Pathways of Xenobiotics (Prakash C, Gau L, Zhong D, Aizawa H, and Lee P, eds), vol. 1, John Wiley & Sons, New York. In press.
28. Guengerich FP, Tang Z, Cheng Q, and Salamanca-Pinzón SG (2011) Approaches to deorphanization of human and microbial cytochrome P450 enzymes. Biochem Biophys Acta 1814: 139-145.
29. Guengerich FP, Tang Z, Salamanca-Pinzón SG, and Cheng Q (2010) Characterizing proteins of unknown function: orphan cytochrome P450 enzymes as a paradigm. Mol Interv 10: 153-163.
30. Guengerich FP and Turvy CG (1991) Comparison of levels of several human microsomal cytochrome P-450 enzymes and epoxide hydrolase in normal and disease states using immunochemical analysis of surgical liver samples. J Pharmacol Exp Ther 256: 1189-1194.
31. Hanson AD, Pribat A, Waller JC, and de Crécy-Lagard V (2010) 'Unknown' proteins and 'orphan' enzymes: the missing half of the engineering parts list-and how to find it. Biochem J 425: 1-11.
32. Humphreys JM and Chapple C (2000) Molecular 'pharming' with plant P450s. Trends Plant Sci 5: 271-272.
33. Isin EM and Guengerich FP (2007) Complex reactions catalyzed by cytochrome P450 enzymes. Biochim Biophys Acta 1770: 314-329.
34. Jakoby WB (1980) Detoxication enzymes, in Enzymatic Basis of Detoxication (Jakoby WB ed), vol. 1, pp 1-6, Academic Press, New York.
35. Kalsotra A, Turman CM, Kikuta Y, and Strobel HW (2004) Expression and characterization of human cytochrome P450 4F11: putative role in the metabolism of therapeutic drugs and eicosanoids. Toxicol Appl Pharmacol 199: 295-304.
36. Kameda S, Maruyama H, Higuchi N, Nakamura G, Iino N, Nishikawa Y, Miyazaki J, and Gejyo F (2003) Hydrodynamics-based transfer of PCR-amplified DNA fragments into rat liver. Biochem Biophys Res Commun 309: 929-936.
37. Karlgren M, Backlund M, Johansson I, Oscarson M, and Ingelman-Sundberg M (2004) Characterization and tissue distribution of a novel human cytochrome P450-CYP2U1. Biochem Biophys Res Commun 315: 679-685.
38. Karlgren M, Gomez A, Stark K, Svärd J, Rodriguez-Antona C, Oliw E, Bernal ML, Ramón y Cajal S, Johansson I, and Ingelman-Sundberg M (2006) Tumor-specific expression of the novel cytochrome P450 enzyme, CYP2W1. Biochem Biophys Res Commun 341: 451-458.
39. Karlgren M, Stark K, Oliw E, and Ingelman-Sundberg M (2005) A novel human cytochrome P450 enzyme, CYP2W1. Analysis of function and distribution. Drug Metab Rev 37: 51.
40. Katajamaa M, Miettinen J, and Oresic M (2006) MZmine: toolbox for processing and visualization of mass spectrometry based molecular profile data. Bioinformatics 22: 634-636.
41. Katajamaa M and Oresic M (2005) Processing methods for differential analysis of LC/MS profile data. BMC Bioinformatics 6: 179.
42. Koskela S, Hakkola J, Hukkanen J, Pelkonen O, Sorri M, Saranen A, Anttila S, Fernandez-Salguero P, Gonzalez F, and Raunio H (1999) Expression of CYP2A genes in human liver and extrahepatic tissues. Biochem Pharmacol 57: 1407-1413.
43. Lai TY, Chu KO, Chan KP, Ng TK, Yam GH, Lam DS, and Pang CP (2010) Alterations in serum fatty acid concentrations and desaturase activities in Bietti crystalline dystrophy unaffected by CYP4V2 genotypes. Invest Ophthalmol Vis Sci 51: 1092-1097.
44. Lamb DC, Guengerich FP, Kelly SL, and Waterman MR (2006) Exploiting Streptomyces coelicolor A3(2) P450s as a model for application in drug discovery. Expert Opin Drug Metab Toxicol 2: 27-40.
45. Lamb DC, Zhao B, Guengerich FP, Kelly SL, and Waterman MR (2011) Genomics of streptomyces cytochrome P450, in Streptomyces: Molecular Biology and Biotechnology, Horizon Press, Hethersett, UK. In press.
46. Lefèvre C, Bouadjar B, Ferrand V, Tadini G, Mégarbané A, Lathrop M, Prud'homme JF, and Fischer J (2006) Mutations in a new cytochrome P450 gene in lamellar ichthyosis type 3. Hum Mol Genet 15: 767-776.
47. Li A, Jiao X, Munier FL, Schorderet DF, Yao W, Iwata F, Hayakawa M, Kanai A, Shy Chen M, Alan Lewis R, et al. (2004) Bietti crystalline corneoretinal dystrophy is caused by mutations in the novel gene CYP4V2. Am J Hum Genet 74: 817-826.
48. Li W, Schuler MA, and Berenbaum MR (2003) Diversification of furanocoumarinmetabolizing cytochrome P450 monooxygenases in two papilionids: specificity and substrate encounter rate. Proc Natl Acad Sci USA 100 (Suppl 2): 14593-14598.
49. Mangelsdorf DJ and Evans RM (1995) The RXR heterodimers and orphan receptors. Cell 83: 841-850.
50. Mansuy D, Bartoli JF, and Momenteau M (1982) Alkane hydroxylation catalyzed by metalloporphyrins: evidence for different active oxygen species with alkylhydroperoxides and iodosobenzene as oxidants. Tetrahedron Lett 23: 2781-2784.
51. McLean KJ, Dunford AJ, Neeli R, Driscoll MD, and Munro AW (2007) Structure, function and drug targeting in Mycobacterium tuberculosis cytochrome P450 systems. Arch Biochem Biophys 464: 228-240.
52. Morant M, Bak S, Møller BL, and Werck-Reichhart D (2003) Plant cytochromes P450: tools for pharmacology, plant protection and phytoremediation. Curr Opin Biotechnol 14: 151-162.
53. Mueller GC and Miller JA (1948) The metabolism of 4-dimethylaminoazobenzene by rat liver homogenates. J Biol Chem 176: 535-544.
54. Nakano M, Kelly EJ, and Rettie AE (2009) Expression and characterization of CYP4V2 as a fatty acid ω-hydroxylase. Drug Metab Dispos 37: 2119-2122.
55. Nebert DW and Russell DW (2002) Clinical importance of the cytochromes P450. Lancet 360: 1155-1162.
56. Nilsson T, Ivanov IV, and Oliw EH (2010) LC-MS/MS analysis of epoxyalcohols and epoxides of arachidonic acid and their oxygenation by recombinant CYP4F8 and CYP4F22. Arch Biochem Biophys 494: 64-71.
57. Nishida CR, Lee M, and de Montellano PR (2010) Efficient hypoxic activation of the anticancer agent AQ4N by CYP2S1 and CYP2W1. Mol Pharmacol 78: 497-502.
58. Niwa T, Murayama N, and Yamazaki H (2009) Oxidation of endobiotics mediated by xenobiotic-metabolizing forms of human cytochrome P450. Curr Drug Metab 10: 700-712.
59. Ortiz de Montellano PR (1995) Oxygen activation and reactivity, in Cytochrome P450: Structure, Mechanism, and Biochemistry, 2nd ed (Ortiz de Montellano PR ed) pp 245-303, Plenum Press, New York.
60. Oscarson M, McLellan RA, Asp V, Ledesma M, Bernal Ruiz ML, Sinues B, Rautio A, and Ingelman-Sundberg M (2002) Characterization of a novel CYP2A7/CYP2A6 hybrid allele (CYP2A6*12) that causes reduced CYP2A6 activity. Hum Mutat 20: 275-283.
61. Poulos TL and Johnson EF (2005) Structures of cytochrome P450 enzymes, in Cytochrome P450: Structure Mechanism, and Biochemistry, 3rd Ed (Ortiz de Montellano PR ed) pp 87-114, Kluwer Academic/Plenum Publishers, New York.
62. Remmer H (1959) [The acceleration of evipan oxidation and the demethylation of methylaminopyrine by barbiturates.] Naunyn Schmiedebergs Arch Exp Pathol Pharmakol 237: 296-307.
63. Rieger MA, Ebner R, Bell DR, Kiessling A, Rohayem J, Schmitz M, Temme A, Rieber EP, and Weigle B (2004) Identification of a novel mammary-restricted cytochrome P450, CYP4Z1, with overexpression in breast carcinoma. Cancer Res 64: 2357-2364.
64. Rivera SP, Saarikoski ST, and Hankinson O (2002) Identification of a novel dioxininducible cytochrome P450. Mol Pharmacol 61: 255-259.
65. Rivera SP, Wang F, Saarikoski ST, Taylor RT, Chapman B, Zhang R, and Hankinson O (2007) A novel promoter element containing multiple overlapping xenobiotic and hypoxia response elements mediates induction of cytochrome P4502S1 by both dioxin and hypoxia. J Biol Chem 282: 10881-10893.
66. Ryan KJ (1958) Conversion of androstenedione to estrone by placental microsomes. Biochim Biophys Acta 27: 658-662.
67. Rylander T, Neve EP, Ingelman-Sundberg M, and Oscarson M (2001) Identification and tissue distribution of the novel human cytochrome P450 2S1 (CYP2S1). Biochem Biophys Res Commun 281: 529-535.
68. Saarikoski ST, Rivera SP, Hankinson O, and Husgafvel-Pursiainen K (2005a) CYP2S1: a short review. Toxicol Appl Pharmacol 207: 62-69.
69. Saarikoski ST, Wikman HA, Smith G, Wolff CH, and Husgafvel-Pursiainen K (2005b) Localization of cytochrome P450 CYP2S1 expression in human tissues by in situ hybridization and immunohistochemistry. J Histochem Cytochem 53: 549-556.
70. Salamanca-Pinzón GS and Guengerich FP (2011) A tricistronic human adrenodoxin reductase-adrenodoxin-cytrochrome P450 27A1 vector system for substrate hydroxylation in Escherichia coli. Protein Expr Purif doi:10.1016/j.pep.2011.05.008.
71. Sanchez-Ponce R and Guengerich FP (2007) Untargeted analysis of mass spectrometry data for elucidation of metabolites and function of enzymes. Anal Chem 79: 3355-3362.
72. Sansen S, Yano JK, Reynald RL, Schoch GA, Griffin KJ, Stout CD, and Johnson EF (2007) Adaptations for the oxidation of polycyclic aromatic hydrocarbons exhibited by the structure of human P450 1A2. J Biol Chem 282: 14348-14355.
73. Savas U, Hsu MH, Griffin KJ, Bell DR, and Johnson EF (2005) Conditional regulation of the human CYP4X1 and CYP4Z1 genes. Arch Biochem Biophys 436: 377-385.
74. Savas U, Hsu MH, and Johnson EF (2003) Differential regulation of human CYP4A genes by peroxisome proliferators and dexamethasone. Arch Biochem Biophys 409: 212-220.
75. Schuler MA (1996) The role of cytochrome P450 monooxygenases in plant-insect interactions. Plant Physiol 112: 1411-1419.
76. Shen AL, O'Leary KA, and Kasper CB (2002) Association of multiple developmental defects and embryonic lethality with loss of microsomal NADPH-cytochrome P450 oxidoreductase. J Biol Chem 277: 6536-6541.
77. Shimada T, Hayes CL, Yamazaki H, Amin S, Hecht SS, Guengerich FP, and Sutter TR (1996) Activation of chemically diverse procarcinogens by human cytochrome P450 1B1. Cancer Res 56: 2979-2984.
78. Shinkyo R and Guengerich FP (2011) Cytochrome P450 7A1 cholesterol 7α-hydroxylation: individual reaction steps in the catalytic cycle and rate-limiting ferric iron reduction. J Biol Chem 286: 4632-4643.
79. Smith CA, Want EJ, O'Maille G, Abagyan R, and Siuzdak G (2006) XCMS: processing mass spectrometry data for metabolite profiling using nonlinear peak alignment, matching, and identification. Anal Chem 78: 779-787.
80. Smith G, Wolf CR, Deeni YY, Dawe RS, Evans AT, Comrie MM, Ferguson J, and Ibbotson SH (2003) Cutaneous expression of cytochrome P450 CYP2S1: individuality in regulation by therapeutic agents for psoriasis and other skin diseases. Lancet 361: 1336-1343.
81. Stark K, Dostalek M, and Guengerich FP (2008a) Expression and purification of orphan cytochrome P450 4X1 and oxidation of anandamide. FEBS J 275: 3706-3717.
82. Stark K, Wu ZL, Bartleson CJ, and Guengerich FP (2008b) Heterologous expression and mRNA distribution of orphan cytochrome P450 20A1. Drug Metab Dispos 36: 1930-1937.
83. Stoilov I, Akarsu AN, and Sarfarazi M (1997) Identification of three different truncating mutations in cytochrome P4501B1 (CYP1B1) as the principal cause of primary congenital glaucoma (Buphthalmos) in families linked to the GLC3A locus on chromosome 2p21. Hum Mol Genet 6: 641-647.
84. Takei K, Yamaya T, and Sakakibara H (2004) Arabidopsis CYP735A1 and CYP735A2 encode cytokinin hydroxylases that catalyze the biosynthesis of transzeatin. J Biol Chem 279: 41866-41872.
85. Tang Z and Guengerich FP (2010) Dansylation of unactivated alcohols for improved mass spectral sensitivity and application to analysis of cytochrome P450 oxidation products in tissue extracts. Anal Chem 82: 7706-7712.
86. Tang Z, Martin MV, and Guengerich FP (2009) Elucidation of functions of human cytochrome P450 enzymes: identification of endogenous substrates in tissue extracts using metabolomic and isotopic labeling approaches. Anal Chem 81: 3071-3078.
87. Tang Z, Salamanca-Pinzón SG, Wu ZL, Xiao Y, and Guengerich FP (2010) Human cytochrome P450 4F11: heterologous expression in bacteria, purification, and characterization of catalytic function. Arch Biochem Biophys 494: 86-93.
88. Taylor M, Lamb DC, Cannell R, Dawson M, and Kelly SL (1999) Cytochrome P450105D1 (CYP105D1) from Streptomyces griseus: heterologous expression, activity, and activation effects of multiple xenobiotics. Biochem Biophys Res Commun 263: 838-842.
89. Tolstikov VV, Lommen A, Nakanishi K, Tanaka N, and Fiehn O (2003) Monolithic silica-based capillary reversed-phase liquid chromatography/electrospray mass spectrometry for plant metabolomics. Anal Chem 75: 6737-6740.
90. Vasiliou V and Gonzalez FJ (2008) Role of CYP1B1 in glaucoma. Annu Rev Pharmacol Toxicol 48: 333-358.
91. Wang A, Savas U, Stout CD, and Johnson EF (2011) Structural characterization of the complex between α-naphthoflavone and human cytochrome P450 1B1. J Biol Chem 286: 5736-5743.
92. Westlind A, Malmebo S, Johansson I, Otter C, Andersson TB, Ingelman-Sundberg M, and Oscarson M (2001) Cloning and tissue distribution of a novel human cytochrome P450 of the CYP3A subfamily, CYP3A43. Biochem Biophys Res Commun 281: 1349-1355.
93. Wienkers LC and Heath TG (2005) Predicting in vivo drug interactions from in vitro drug discovery data. Nat Rev Drug Discov 4: 825-833.
94. i/AUC) ratios. Drug Metab Dispos 32: 1201-1208.
95. Wu ZL, Bartleson CJ, Ham AJ, and Guengerich FP (2006a) Heterologous expression, purification, and properties of human cytochrome P450 27C1. Arch Biochem Biophys 445: 138-146.
96. Wu ZL, Sohl CD, Shimada T, and Guengerich FP (2006b) Recombinant enzymes over-expressed in bacteria show broad catalytic specificity of human cytochrome P450 2W1 and limited activity of human cytochrome P450 2S1. Mol Pharmacol 69: 2007-2014.
97. Xiao Y, Shinkyo R, and Guengerich FP (2011) Cytochrome P450 2S1 is reduced by NADPH-cytochrome P450 reductase. Drug Metab Dispos 39: 944-946.
98. Yamano S, Tatsuno J, and Gonzalez FJ (1990) The CYP2A3 gene product catalyzes coumarin 7-hydroxylation in human liver microsomes. Biochemistry 29: 1322-1329.
99. Yang X, Zhang B, Molony C, Chudin E, Hao K, Zhu J, Gaedigk A, Suver C, Zhong H, Leeder JS, et al. (2010) Genetic and genomic analysis of cytochrome P450 enzyme activities in human liver. Genome Res 20: 1020-1036.
100. Yoshioka H, Kasai N, Ikushiro S, Shinkyo R, Kamakura M, Ohta M, Inouye K, and Sakaki T (2006) Enzymatic properties of human CYP2W1 expressed in Escherichia coli. Biochem Biophys Res Commun 345: 169-174.
101. Yu AM, Idle JR, and Gonzalez FJ (2004) Polymorphic cytochrome P450 2D6: humanized mouse model and endogenous substrates. Drug Metab Rev 36: 243-277.
102. Yu AM, Idle JR, Herraiz T, Küpfer A, and Gonzalez FJ (2003) Screening for endogenous substrates reveals that CYP2D6 is a 5-methoxyindolethylamine O-demethylase. Pharmacogenetics 13: 307-319.
103. Yokoi Y, Nakazawa M, Mizukoshi S, Sato K, Usui T, and Takeuchi K (2010) Crystal deposits on the lens capsules in Bietti crystalline corneoretinal dystrophy associated with a mutation in the CYP4V2 gene. Acta Ophthalmol 88: 607-609.
104. Yuan X, Ta TC, Lin M, Evans JR, Dong Y, Bolotin E, Sherman MA, Forman BM, and Sladek FM (2009) Identification of an endogenous ligand bound to a native orphan nuclear receptor. PloS one 4: e5609.
105. Zöllner A, Dragan CA, Pistorius D, Müller R, Bode HB, Peters FT, Maurer HH, and Bureik M (2009) Human CYP4Z1 catalyzes the in-chain hydroxylation of lauric acid and myristic acid. Biol Chem 390: 313-317.