The flavin-containing monoooxygenases (FMOs): Genetic variation and its consequences for the metabolism of therapeutic drugs

Current Pharmacogenomics

Volumn 5, Issue 4, 2007, Pages 292-313

  Philips, Ian R ^a   Francois, Asvi A ^b   Shephard, Elizabeth A ^b  

^a QUEEN MARY UNIVERSITY OF LONDON   (United Kingdom)

^b UNIVERSITY COLLEGE LONDON   (United Kingdom)

Author keywords

Coding variants; Cytochrome P450; FMO2 expression; Human FMO1 gene; Trimethylaminuria

Indexed keywords

5 (2,4 DIOXO 5 THIAZOLIDINYLMETHYL) 2 METHOXY N [4 (TRIFLUOROMETHYL)BENZYL]BENZAMIDE; ANTIBIOTIC AGENT; ANTIRHEUMATIC AGENT; BENZYDAMINE; CHLORPROMAZINE; CLOZAPINE; DIMETHYLANILINE MONOOXYGENASE; DIMETHYLANILINE MONOOXYGENASE 1; DIMETHYLANILINE MONOOXYGENASE 2; DIMETHYLANILINE MONOOXYGENASE 3; DIMETHYLANILINE MONOOXYGENASE 4; DIMETHYLANILINE MONOOXYGENASE 5; ETHIONAMIDE; IMIPRAMINE; ITOPRIDE; N (2 DIMETHYLAMINOETHYL) 9 HYDROXY 5,6 DIMETHYL 6H PYRIDO[4,3 B]CARBAZOLE 1 CARBOXAMIDE; OLOPATADINE; PLACEBO; RANITIDINE; S METHYL ESONARIMOD; SELEGILINE; SULINDAC; SULINDAC SULFIDE; TAMOXIFEN; TAZAROTENE; THIAMAZOLE; THIOACETAZONE; TRIFLUOPERAZINE; UNCLASSIFIED DRUG; UNINDEXED DRUG; UNSPECIFIC MONOOXYGENASE;

ADENOMATOUS POLYP; AFRICAN AMERICAN; AMINO ACID SEQUENCE; BREAST CANCER; CATALYSIS; CLINICAL TRIAL; DIET RESTRICTION; DNA FLANKING REGION; DRUG EFFICACY; DRUG METABOLISM; DRUG OXIDATION; DRUG RESPONSE; ENZYME ACTIVITY; ENZYME ANALYSIS; ENZYME SPECIFICITY; EVIDENCE BASED MEDICINE; GENE EXPRESSION PROFILING; GENE MUTATION; GENETIC ORGANIZATION; GENETIC POLYMORPHISM; GENETIC VARIABILITY; HOMOZYGOSITY; HUMAN; LIVER TOXICITY; METABOLIC DISORDER; MUTATIONAL ANALYSIS; NONHUMAN; NUCLEOTIDE SEQUENCE; PHARMACOGENETICS; PROTEIN EXPRESSION; RACE DIFFERENCE; REVIEW; SINGLE NUCLEOTIDE POLYMORPHISM; SPECIES COMPARISON; TISSUE DISTRIBUTION; TISSUE SPECIFICITY; TRIMETHYLAMINURIA; TUBERCULOSIS;

EID: 37249028167     PISSN: 15701603     EISSN: None     Source Type: Journal    
DOI: 10.2174/157016007782793683     Document Type: Review

References (162)

1. Akerman, B. R.; Lemass, H.; Chow, L. M.; Lambert, D. M.; Greenberg, C.; Bibeau, C.; Mamer, O. A. and Treacy, E. P. (1999a) Trimethy-laminuria is Caused by Mutations of the FMO3 Gene in a North American Cohort. Mol. Genet. Metab. 68, 24-31.
2. Akerman, B. R.; Forrest, S.; Chow, L.; Youil, R.; Knight, M. and Treacy, E. P. (1999b) Two Novel Mutations of the FMO3 Gene in a Proband with Trimethylaminuria. Hum. Mutat. 13, 376-379.
3. Allerston, C. K.; Shimizu, M.; Fujieda, M.; Shephard, E. A.; Yamazaki, H. and Phillips, I. R. (2007) Molecular Evolution and Balancing Selection in the Flavin-Containing Monooxygenase 3 Gene (FMO3). Pharmacogenet. Genomics 17, 827-839.
4. Al-Waiz, M.; Ayesh, R.; Mitchell, S. C.; Idle, J. R. and Smith, R. L. (1988) Trimethylaminuria fFish-Odour Syndrome'): A Study of an Affected Family. Clin. Sci. 74, 231-236.
5. Attar, M.; Dong, D.; Ling, K. H. and Tang-Liu, D. D. (2003) Cytochrome P450 2C8 and Flavin-Containing Monooxygenases Are Involved in the Metabolism of Tazarotenic Acid in Humans. Drug Metab. Dispos. 31, 476-481.
6. Basarab, T.; Ashton, G. H.; Menage, H. P. and McGrath, J. A. (1999) Sequence Variations in the Flavin-Containing Mono-Oxygenase 3 Gene (FMO3) in Fish Odour Syndrome. Br. J. Dermatol. 140, 164-167.
7. Bieche, I.; Girault, I.; Urbain, E.; Tozlu, S. and Lidereau, R. (2004) Relationship between Intratumoral Expression of Genes Coding for Xenobiotic-Metabolizing Enzymes and Benefit from Adjuvant Tamoxifen in Estrogen Receptor Alpha-Positive Postmenopausal Breast Carcinoma. Breast Cancer Res. 6, R252-263.
8. Brunelle, A.; Bi, Y. A.; Lin, J.; Russell, B.; Loy, L.; Berkman, C. and Cashman, J. (1997) Characterization of Two Human Flavin-Containing Monooxygenase (Form 3) Enzymes Expressed in Escherichia Coli as Maltose Binding Protein Fusions. Drug Metab. Dispos. 25, 1001-1007.
9. Cashman, J. R. (2002) Human Flavin-Containing Monooxygenase (Form 3): Polymorphisms and Variations in Chemical Metabolism. Pharmacogenomics 3, 325-329.
10. Cashman, J. R. (2004) The Implications of Polymorphisms in Mammalian Flavin-Containing Monooxygenases in Drug Discovery and Development. Drug Discov. Today 9, 574-581.
11. Cashman, J. R. and Zhang, J. (2002) Interindividual Differences of Human Flavin-Containing Monooxygenase 3: Genetic Polymorphisms and Functional Variation. Drug Metab. Dispos. 30, 1043-1052.
12. Cashman, J. R. and Zhang, J. (2006) Human Flavin-Containing Monooxygenases. Ann. Rev. Pharmacol. Toxicol. 46, 65-100.
13. Cashman, J. R.; Bi, Y. A.; Lin, J.; Youil, R.; Knight, M.; Forrest, S. and Treacy, E. (1997) Human Flavin-Containing Monooxygenase Form 3: cDNA Expression of the Enzymes Containing Amino Acid Substitutions Observed in Individuals with Trimethylaminuria. Chem. Res. Toxicol. 10, 837-841.
14. Cashman, J. R.; Xiong, Y. N.; Xu, L. and Janowsky, A. (1999) N-Oxygenation of Amphetamine and Methamphetamine by the Human Flavin-Containing Monooxygenase (Form 3): Role in Bioactivation and Detoxication. J. Pharmacol. Exp. Ther. 288, 1251-1260.
15. Cashman, J. R.; Zhang, J.; Leushner, J. and Braun, A. (2001) Population Distribution of Human Flavin-Containing Monooxygenase Form 3: Gene Polymorphisms. Drug Metab. Dispos. 29, 1629-1637.
16. Cereda, C.; Gabanti, E.; Corato, M.; de Silvestri, A.; Alimonti, D.; Cova, E.; Malaspina, A. and Ceroni, M. (2006) Increased Incidence of FMO1 Gene Single Nucleotide Polymorphisms in Sporadic Amyotrophic Lateral Sclerosis. Amyotroph. Lateral Scler. 7, 227-234.
17. Chen, Q. M.; Alexander, D.; Sun, H.; Xie, L.; Lin, Y.; Terrand, J.; Morrissy, S. and Purdom, S. (2005) Corticosteroids Inhibit Cell Death Induced by Doxorubicin in Cardiomyocytes: Induction of Antiapoptosis, Antioxidant, and Detoxification Genes. Mol. Pharmacol. 67, 1861-1873.
18. Cherrington, N. J.; Falls, J. G.; Rose, R. L.; Clements, K. M.; Philpot, R. M.; Levi, P. E. and Hodgson, E. (1998a) Molecular Cloning, Sequence, and Expression of Mouse Flavin-Containing Mon0oxygenases 1 and 5 (FMO1 and FMO5). J. Biochem. Mol. Toxicol. 12, 205-212.
19. Cherrington, N. J.; Cao, Y.; Cherrington, J. W.; Rose, R. L. and Hodgson, E. (1999b) Physiological Factors Affecting Protein Expression of Flavin-Containing Monooxygenases 1, 3 and 5. Xenobiotica 28, 673-682.
20. Chung, W. G.; Park, C. S.; Roh, H. K. and Cha, Y. N. (1997) Induction of Flavin-containing Monooxygenase (FMO1) by a Polycyclic Aromatic Hydrocarbon, 3-Methylcholandimne, in Rat Liver. Mol. Cells 7, 738-741.
21. Chung, W. G.; Park, C. S.; Roh, H. K.; Lee, W. K. and Cha, Y. N. (2000) Oxidation of Ranitidine by Isozymes of Flavin-Containing Monooxygenase and Cytochrome P450. Jpn. J. Pharmacol. 84, 213-220.
22. Dolphin, C.; Shephard, E. A.; Povey, S.;,Palmer, C. N.; Ziegler, D. M.; Ayesh, R.; Smith, R. L. and Phillips, I. R. (1991) Cloning, Primary Sequence, and Chromosomal Mapping of a Human Flavin-Containing Monooxygenase (FMO1). J. Biol. Chem. 266, 12379-12385.
23. Dolphin, C. T.; Shephard, E. A.; Povey, S.; Smith, R. L. and Phillips, I. R. (1992) Cloning, Primary Sequence and Chromosomal Localization of Human FMO2, a New Member of the Flavin-Containing Mono-Oxygenase Family. Biochem. J. 287, 261-267.
24. Dolphin, C. T.; Cullingford, T. E.; Shephard, E. A.; Smith, R. L. and Phillips, I. R. (1996) Differential Developmental and Tissue-Specific Regulation of Expression of the Genes Encoding Three Members of the Flavin-Containing Monooxygenase Family of Man, FMO1, FMO3 and FMO4. Eur. J. Biochem. 235, 683-689.
25. Dolphin, C. T.; Riley, J. H.; Smith, R. L.; Shephard, E. A. and Phillips, I. R. (1997a) Structural Organization of the Human Flavin-Containing Monooxygenase 3 Gene (FMO3), the Favored Candidate for Fish-Odor Syndrome, Determined Directly from Genomic DNA. Genomics 46, 260-267.
26. Dolphin, C. T.; Jamnohamed, A.; Smith, R. L.; Shephard, E. A. and Phillips, I. R. (1997b) Missense Mutation in Flavin-Containing Mono-Oxygenase 3 Gene, FMO3, Underlies Fish-Odour Syndrome. Nat. Genet. 17, 491-494.
27. Dolphin, C. T.; Beckett, D. J.; Janmohamed, A.; Cullingford, T. E.; Smith, R. L.; Shephard, E. A. and Phillips, I. R. (1998) The Flavin-Containing Monooxygenase 2 Gene (FMO2) of Humans, but Not of Other Primates, Encodes a Truncated, Nonfunctional Protein. J. Biol. Chem. 273, 30599-30607.
28. Dolphin, C. T.; Janmohamed, A.; Smith, R. L.; Shephard, E. A. and Phillips, I. R. (2000) Compound Heterozygosity for Missense Mutations in the Flavin-Containing Monooxygenase 3 (FMO3) Gene in Patients with Fish-Odour Syndrome. Pharmacogenetics 10, 799-807.
29. Duescher, R. J.; Lawton, M. P.; Philpot, R. M. and Elfarra, A. A. (1994) Flavin-Containing Monooxygenase (FMO)-Dependent Metabolism of Methionine and Evidence for FMO3 Being the Major FMO Involved in Methionine Sulfoxidation in Rabbit Liver and Kidney Microsomes. J. Blol. Chem. 269, 17525-17530.
30. Duggan, D. E.; Hooke, K. F.; Risley, E. A.; Shen, T. Y. and Arman, C. G. (1977) Identification of the Biologically Active Form of Sulindac. J. Pharmacol. Exp. Ther. 201, 8-13.
31. Eswaramoorthy, S.; Bonanno, J. B.; Burley, S. K. and Swaminathan, S. (2006). Mechanism of Action of a Flavin-Containing Monooxygenase. Proc. Natl. Acad. Sci. USA 103, 9832-9837.
32. Etienne, F.; Resnick, L.; Sagher, D.; Brot, N. and Weissbach, H. (2003) Reduction of Sulindac to Its Active Metabolite, Sulindac Sulfide: Assay and Role of the Methionine Sulfoxide Reductase System. Biochem. Biophys. Res. Commun. 312, 1005-1010.
33. Fang, J.; Coutts, R. T.; McKenna, K. F. and Baker, G. B. (1998) Elucidation of Individual Cytochrome P450 Enzymes Involved in the Metabolism of Clozapine. Naunyn Schmiedebergs Archiv. Pharmacol. 358, 592-599.
34. Forrest, S. M.; Knight, M.; Akerman, B. R.; Cashman, J. R. and Treacy, E. P. (2001) A Novel Deletion in the Flavin-Containing Monooxygenase Gene (FMO3) in a Greek Patient with Trimethylaminuria. Pharmacogenetics 11, 169-174.
35. Fujieda, M.; Yamazaki, H.; Togashi, M.; Saito, T. and Kamataki, T. (2003) Two Novel Single Nucleotide Polymorphisms (SNPs) of the FMO3 Gene in Japanese. Drug Metab. Pharmacokinet. 18, 333-335.
36. Furnes, B. and Schlenk, D. (2004) Evaluation of Xenobiotic N- and S-Oxidation by Variant Flavin-Containing Monooxygenase 1 (FMO1) Enzymes. Toxicol Sci. 78, 196-203.
37. Furnes, B.; Feng, J.; Sommer, S. S. and Schlenk, D. (2003) Identification of Novel Variants of the Flavin-Containing Monooxygenase Gene Family in African Americans. Drug Metab. Dispos. 31, 187-193.
38. Gasser, R.; Tynes, R. E.; Lawton, M. P.; Korsmeyer, K. K.; Ziegler, D. M. and Philpot, R. M. (1990) The Flavin-Containing Monooxygenase Expressed in Pig Liver. Primary Sequence, Distribution, and Evidence for a Single Gene. Biochemistry 29, 119-124.
39. Hadidi, H. F.; Cholerton, S.; Atkinson, S.; Irshaid, Y. M.; Rawashdeh, N. M. and Idle, J. R. (1995) The N-Oxidation of Trimethylamine in a Jordanian Population. Br. J. Clin. Pharmacol. 39, 179-181.
40. Hamman, M. A.; Haehner-Daniels, B. D.; Wrighton, S. A.; Rettie, A. E. and Hall, S. D. (2000) Stereoselective Sulfoxidation of Sulindac Sulfide by Flavin-Containing Monaoxygensses. Comparison of Human Liver and Kidney Microsomes and Mammalian Enzymes. Biochem. Pharmacol. 60, 7-17.
41. Henderson, M. C.; Krueger, S. K.; Siddens, L. K.; Stevens, J. F. and Williams, D. E. (2004a) S-Oxygenation of the Thioether Organophosphate Insecticides Phorate and Disulfoton by Human Lung Flavin-Containing Monooxygenase 2. Biochem. Pharmacol. 68, 959-967.
42. Henderson, M. C.; Krueger, S. K.; Stevens, J. F. and Williams, D. E. (2004b) Human Flavin-Contaming Monooxygenase Form 2 S-Oxygenation: Sulfenic Acid Formation from Thioureas and Oxidation of Glutathionc. Chem. Res. Toxicol. 17, 633-640.
43. Hernandez, D.; Addou, S.; Lee, D.; Orengo, C.; Shephard, E. A. and Phillips, I. R. (2003) Trimethylaminuria and a Human FMO3 Mutation Database. Hum. Mut. 22, 209-213.
44. Hernandez, D.; Janmohamed, A.; Chandan, P.; Phillips, I. R. and Shephard, E. A. (2004) Organization and Evolution of the Flavin-Containing Monooxygenase Genes of Human and Mouse: Identification of Novel Gene and Pseudogene Clusters. Pharmacogenetics 14, 117-130.
45. Hines, R. N.; Hopp, K. A.; Franco, J.; Saeian, K. and Begun, F. P. (2002) Alternative Processing of the Human FMO6 Gene Renders Transcripts Incapable of Encoding a Functional Flavin-Containing Monooxygenase. Mol. Pharmacol. 62, 320-325.
46. Hines, R. N.; Luo, Z.; Hopp, K. A.; Cabacungan, E. T.; Koukouritaki, S. B. and McCarver, D. G. (2003) Genetic Variability at the Human FMO1 Locus: Significance of a Basal Promoter Yin Yang 1 Element Polymorphism (FMO1*6). J. Pharmacol. Exp. Ther. 306, 1210-1218.
47. Hisamuddin, I. M.; Wehbi, M. A.; Chao, A.; Wyre, H. W.; Hylind, L. M.; Giardiello, F. M. and Yang, V. W. (2004) Genetic Polymorphisms of Human Flavin Monooxygenase 3 in Sulindac-Mediated Primary Chemoprevention of Familial Adenomatous Polyposis. Clin. Cancer Res. 10, 8357-8362.
48. Hisamuddin, I. M.; Wehbi, M. A.; Schmintzer, B.; Easley, K. A.; Hylind, L. M.; Giardiello, F. M. and Yang, V. W. (2005) Genetic Polymorphisms of Flavin Monooxygenase 3 in Sulindac-Induced Regression of Colorectal Adenomas in Familial Adenomatous Polyposis. Cancer Epidemiol. Biomarkers Prev. 14, 2366-2369.
49. Hodgson, E.; Rose, R. L.; Cao, Y.; Dehal, S. S. and Kupfer, D. (2000) Flavin-Containing Monooxygenase Isoform Specificity for the N-Oxidation of Tamoxifen Determined by Product Measurement and Nadph Oxidation. J. Biochem. Mol. Toxicol. 14, 118-120.
50. Hugonnard, M.; Benoit, E.; Longin-Sauvageon, C. and Lattard, V. (2004) Identification and Characterization of the FMO2 Gene in Rattus Norvegicus: A Good Model to Study Metabolic and Toxicological Consequences of the FMO2 Polymorphism. Pharmacogenetics 14, 647-655.
51. Itagaki, K.; Carver, G. T. and Philpot, R. M. (1996) Expression and Characterization of a Modified Flavin-Containing Monooxygenase 4 from Humans. J. Biol. Chem. 271, 20102-20107.
52. Jacobsen, W.; Christians, U. and Benet, L. Z. (2000) In Vitro Evaluation of the Disposition of a Novel Cysteine Protease Inhibitor [in Process Citation]. Drug Metab. Dispos. 28, 1343-1351.
53. Jakobsson, S. V. and Cintig, D. L. (1973) Studies on the Cytochrome P450-Containing Mono-Oxygenase System in Human Kidney Cortex Microsomes. J. Pharmacol. Exp. Ther. 185, 226-234.
54. Janmohamed, A.; Dolphin, C. T.; Phillips, I. R. and Shephard, E. A. (2001) Quantification and Cellular Localization of Expression in Human Skin of Genes Encoding Flavin-Containing Monooxygenases and Cytochromes P450. Biochem. Pharmacol. 62, 777-786.
55. Janmohamed, A.; Hernandez, D.; Phillips, I. R. and Shephard, E. A. (2004) Cell-, Tissue-, Sex- and Developmental Stage-Specific Expression of Mouse Flavin-Containing Monooxygenases (FMOs). Biochem. Pharmacol. 68, 73-83.
56. Jones, K. C. and Ballou, D. P. (1986) Reactions of the 4a-Hydroperoxide of Liver Microsomal Flavin-Containing Monooxygenase with Nucleophilic and Electrophilic Substrates. J. Mol. Chem. 261, 2553-2559.
57. Kajita, J.; Enano, K.; Fuse, E.; Kuwabara, T. and Kobayashi, H. (2002) Effects of Olopatadine, a New Antiallergic Agent, on Human Liver Microsomal Cytochrome P450 Activities. Drug Metab. Dispos. 30, 1504-1511.
58. Kang, J. H.; Chung, W. G.; Lee, K. H.; Park, C. S.; Kang, J. S.; Shin, I. C.; Roh, H. K.; Dong, M. S.; Baek, H. M. and Cha, Y. N. (2000) Phenotypes of Flavin-Containing Monooxygenase Activity Determined by Ranitidine N-Oxidation Are Positively Correlated with Genotypes of Linked FMO3 Gene Mutations in a Korean Population. Pharmacogenetics 10, 67-78.
59. Karanam, B. V.; Hop, C. E.; Liu, D. Q.; Wallace, M.; Dean, D.; Satoh, H.; Komuro, M.; Awano, K. and Vincent, S. H. (2004) In Vitro Metabolism of Mk-0767 [(+/-)-5-[(2,4-Dioxothiazohdin-5-Yl)Methyl]- 2-Methoxy-N-(4-Trifluoromet Hyl) Phenyl]Methyl]Benzamide], a Peroxisome Proliferator-Activated Receptor Alpha/Gamma Agonist. I. Role of Cytochrome P450, Methyltransferases, Flavin Monooxygenases, and Esterases. Drug Metab. Dispos. 32, 1015-1022.
60. Katchamart, S.; Stresser, D. M.; Dehal, S. S.; Kupfer, D. and Williams, D. E. (2000) Concurrent Flavin-containing Monooxygenase Down-regulation and Cytochrome P-450 Induction by Dietary Indoles in Rat: Implications for Drug-drug Interaction. Drug Metab. Dispos. 28, 930-936.
61. Kim, Y. H.; Lim, D. S.; Lee, J. H.; Shim, W. J.; Ro, Y. M.; Park, G. H.; Becker, K. G.; Cho-Chung, Y. S. and Kim, M. K. (2003) Gene Expression Profiling of Oxidative Stress on Atrial Fibrillation in Humans. Exp. Mol. Med. 35, 336-349.
62. Kim, Y. M. and Ziegler, D. M. (2000) Size Limits of Thiocarbamides Accepted as Substrates by Human Flavin- Containing Monooxygenase 1. Drug Metab. Dispos. 28, 1003-1006.
63. Kliewer, S. A.; Lehmann, J. M.; Milburn, M. V. and Willson, T. M. (1999) The PPARs and PXRs: Nuclear Xenobiotic Receptors That Define Novel Hormone Signaling Pathways. Recent Prog. Horm. Res. 54, 345-367.
64. Kobayashi, S.; Kim, J.; Lawley, H.; Tjoa, S.; Fennessey, P.; Preti, G. and Fakharzadeh, S. (2001) Identification of a Novel D132H Missense Mutation in the Flavin-Containing Monoosygenase 3 Gene in Trimethylaminuria. J. Invest. Dermatol. 117, 789.
65. Koukouritaki, S. B. and Hines, R. N. (2005) Flavin-Containing Monooxygenase Genetic Polymorphism: Impact on Chemical Metabolism and Drug Development. Pharmacogenomics 6, 807-822.
66. Koukouritaki, S. B.; Simpson, P.; Yeung, C. K.; Rettie, A. E. and Hines, R. N. (2002) Human Hepatic Flavin-Containing Monooxygenases 1 (FMO1) and 3 (FMO3) Developmental Expression. Pediarr. Res. 51, 236-243.
67. Koukouritaki, S. B.; Poch, M. T.; Cabacungan, E. T.; McCarver, D. G. and Hines, R. N. (2005) Discovery of Novel Flavin-Containing Monooxygenase 3 (FMO3) Single Nucleotide Polymorphisms and Functional Analysis of Upstream Haplotype Variants. Mol. Pharmacol. 68, 383-392.
68. Koukouritaki, S. B.; Poch, M. T.; Henderson, M. C.; Siddens, L. K.; Krueger, S. K.; VanDyke, J. E.; Williams, D. E.; Pajewski, N. M.; Wang, T. and Hines, R. N. (2007) Identification and Functional Analysis of Common Human Flavin-Containing Monooxygenase 3 Genetic Variants. J. Pharmacol. Exp. Ther. 320, 266-273.
69. Krause, R. J.; Lash, L. H. and Elfarra, A. A. (2003) Human Kidney Flavin-Containing Monooxygenases and Their Potential Roles in Cysteine S-Conjugate Metabolism and Nephrotoxicity. J. Pharmacol. Exp. Ther. 304, 185-191.
70. Krueger, S. K. and Williams, D. E. (2005) Mammalian Flavin-Containing Monooxygenases: Structure/Function, Genetic Polymorphisms and Role in Drug Metabolism. Pharmacol. Ther. 106, 357-387.
71. Krueger, S. K.; Williams, D. E.; Yueh, M. F.; Martin, S. R.; Hines, R. N.; Raucy, J. L.; Dolphin, C. T.; Shephard, E. A. and Phillips, I. R. (2002a) Genetic Polymorphisms of Flavin-Containing Monooxygenase (FMO). Drug Metab. Rev. 34, 523-532.
72. Krueger, S. K.; Martin, S. R.; Yueh, M. F.; Pereira, C. B. and Williams, D. E. (2002b) Identification of Active Flavin-Containing Monooxygenase Isoform 2 in Human Lung and Characterization of Expressed Protein. Drug Metab. Dispos. 30, 34-41.
73. Krueger, S. K.; Siddens, L. K.; Martin, S. R.; Yu, Z.; Pereira, C. B.; Cabacungan, E. T.; Hines, R. N.; Ardlie, K. G.; Raney, J. L. and Williams, D. E. (2004) Differences in FMO2*1 Alletic Frequency between Hispanics of Puerto Rican and Mexican Descent. Drug Metab. Dispos. 32, 1337-1340.
74. Krueger, S. K.; Siddens, L. K.; Henderson, M. C.; Andreasen, E. A.; Tanguay, R. L.; Pereira, C. B.; Cabacungan, E. T.; Hines, R. N.; Ardlie, K. G. and Williams, D. E. (2005) Haplotype and Functional Analysis of Four Flavin-Containing Monooxygenase Isoform 2 (FMO2) Potymorphisms in Hispanics. Pharmacogenet. Genomics 15, 245-256.
75. Krueger, S. K.; Vandyke, J. E.; Williams, D. E. and Hines, R. N. (2006) The Role of Flavin-Containing Monooxygenase (FMO) in the Metabolism of Tamoxifen and Other Tertiary Amines. Drug Metab. Rev. 38, 139-147.
76. Krusekopf, S. and Roots, I. (2005) St John's Wort and Its Constituent Hyperforin Concordantly Regulate Expression of Genes Encoding Enzymes Involved in Basic Cellular Pathways. Pharmacogenet. Genomics 15, 817-829.
77. Kubota, M.; Nakamoto, Y.; Nakayama, K.; Ujjin, P.; Satarug, S.; Mushiroda, T.; Yokoi, T.; Funayama, M. and Kamataki, T. (2002) A Mutation in the Flavin-Containing Monooxygenase 3 Gene and Its Effects on Catalytic Activity for N-Oxidation of Trimethylamine in Vitro. Drug Metab. Pharmacokinet. 17, 207-213.
78. Kulkarni, A. P. and Hodgson, E. (1984) The Metabolism of Insecticides: The Role of Monooxygenase Enzymes. Annu. Rev. Pharmacol. Toxicol. 24, 19-42.
79. Lang, D. H. and Rettie, A. E. (2000) In Vitro Evaluation of Potential in Vivo Probes for Human Flavin- Containing Monooxygenase (FMO): Metabolism of Benzydamine and Caffeine by FMO and P450 Isoforms. Br. J. Clin. Pharmacol. 50, 311-314.
80. Lang, D. H.; Yeung, C. K.; Peter, R. M.; Ibarra, C.; Gasser, R.; Itagaki, K.; Philpot, R. M. and Rettie, A. E. (1998) Isoform Specificity of Trimethylamine N-Oxygenation by Human Flavin-Containing Monooxygenase (FMO) and P450 Enzymes: Selective Catalysis by FMO3. Biochem. Pharmacol. 56, 1005-1012.
81. Lattard, V.; Longin-Sauvageon, C.; Lachuer, J.; Delatour, P. and Benoit, E. (2002a) Cloning, Sequencing, and Tissue-Dependent Expression of Flavin-Containing Monooxygenase (FMO) 1 and FMO3 in the Dog. Drug Metab. Dispos. 30, 119-128.
82. Lattard, V.; Longin-Sauvageon, C.; Krueger, S. K.; Williams, D. E. and Benoit, E. (2002b) The FMO2 Gene of Laboratory Rats, as in Most Humans, Encodes a Truncated Protein. Biochem. Biophys. Res. Commun. 292, 558-563.
83. Lattard, V.; Zhang, J.; Tran, Q.; Furnes, B.; Schlenk, D. and Cashman, J. R. (2003) Two New Polymorphisms of the FMO3 Gene in Caucasian and African-American Populations: Comparative Genetic and Functional Studies. Drug Metab. Dispos. 31, 854-860.
84. Lattard, V.; Zhang, J. and Cashman, J. R. (2004) Alternative Processing Events in Human FMO Genes. Mol. Pharmacol. 65, 1517-1525.
85. Lawton, M. P.; Gasser, R.; Tynes, R. E.; Hodgson, E. and Philpot, R. M. (1990) The Flavin-Containing Monooxygenase Enzymes Expressed in Rabbit Liver and Lung Are Products of Related but Distinctly Different Genes. J. Biol. Chem. 265, 5855-5861.
86. Lawton, M. P.; Cashman, J. R.; Cresteil, T.; Dolphin, C. T.; Elfarra, A. A.; Hines, R. N.; Hodgson, E.; Kimura, T.; Ozols, J.; Phillips, I. R.; Philpot, R. M.; Poulsen, L. L.; Rettie, A. E.; Shephard, E. A.; Williams, D. E. and Ziegler, D. M. (1994) A Nomenclature for the Mammalian Flavin-Containing Monooxygenase Gene Family Based on Amino Acid Sequence Identities. Arch. Biochem. Biophys. 308, 254-257.
87. Lien, E. A.; Solheim, E. and Ueland, P. M. (1991) Distribution of Tamoxifen and Its Metabolites in Rat and Human Tissues During Steady-State Treatment. Cancer Res. 51, 4837-4844.
88. Lomri, N.; Gu, Q. and Cashman, J. R. (1992) Molecular Cloning of the Flavin-Containing Monooxygenase (Form II) cDNA from Adult Human Liver. Proc. Natl. Acad. Sci. USA 89, 1685-1689.
89. Lomri, N.; Yang, Z. and Cashman, J. R. (1993) Regio- and Stereoselective Oxygenations by Adult Human Liver Flavin-Containing Monooxygenase 3. Comparison with Forms 1 and 2. Chem. Res. Toxicol. 6, 800-807.
90. Luo, Z. and Hines, R. N. (2001) Regulation of Flavin-Containing Monooxygenase 1 Expression by Ying Yang 1 and Hepatic Nuclear Factors 1 and 4. Mol. Pharmacol. 60, 1421-1430.
91. Malaspina, A.; Kaushik, N. and de Belleroche, J. (2001) Differential Expression of 14 Genes in Amyotrophic Lateral Sclerosis Spinal Cord Detected Using Gridded Cdna Arrays. J. Neurochem. 77, 132-145.
92. Mayatepek, E. and Kohlmüller, D. (1998) Transient Trimethylaminuria in Childhood. Acta Paediatr. 87, 1205-1207.
93. Mayatepek, E.; Flock, B. and Zschocke, J. (2004) Benzydamine Metabolism in vivo is Impaired in Patients with Deficiency of Flavin-Containing Monooxygenase 3. Pharmacogenetics 14, 775-777.
94. Mazon Ramos, A.; Gil-Setas, A.; Berrade Zubiri, S.; Bandres Echeverri, T.; Wevers, R.; Engelke, U. and Zschocke, J. (2003) Primary Trimethylaminuria or Fish Odor Syndrome. A Novel Mutation in the First Documented Case in Spain. Med. Clin. (Barc.) 120, 219-221.
95. M'Combie, R. R.; Dolphin, C. T.; Povey, S.; Phillips, I. R. and Shephard, E. A. (1996) Localization of Human Flavin-Containing Monooxygenase Genes FMO2 and FMO5 to Chromosome lq. Genomics 34, 426-429.
96. Miller, M. M.; James, R. A.; Richer, J. K.; Gordon, D. F.; Wood, W. M. and Horwitz, K. B. (1997) Progesterone Regulated Expression of Flavin-Containing Monooxygenase 5 by the B-Isoform of Progesterone one Receptors: Implications for Tamoxifen Carcinogenicity. J. Clin. Endocrinol. Metab. 82, 2956-2961.
97. Mitchell, S. C. and Smith, R. L. (2001) Trimethylaminuria: The Fish Malodor Syndrome. Drug Metab. Dispos. 29, 517-521.
98. Mitchell, S. C.; Zhang, A. Q.; Barrett, T.; Ayesh, R. and Smith, R. L. (1997) Studies on the Discontinuous N-Oxidation of Trimethylamine among Jordanian, Ecuadorian and New Guinean Populations. Pharmacogenetics 7, 45-50.
99. Moore, L. B.; Goodwin, B.; Jones, S. A.; Wisely, G. B.; Serabjit-Singh, C. J.; Willson, T. M.; Collins, J. L. and Kliewer, S. A. (2000) St. John's Wort Induces Hepatic Drug Metabolism through Activation of the Pregnane X Receptor. Proc. Natl. Acad. Sci. USA 97, 7500-7502.
100. Murphy, H. C.; Dolphin, C. T.; Janmohamed, A.; Holmes, H. C.; Michelakakis, H.; Shephard, E. A.; Chalmers, R. A.; Phillips, I. R. and Iles, R. A. (2000) A Novel Mutation in the Flavin-Containing Monooxygenase 3 Gene, FMO3, That Causes Fish-Odour Syndrome: Activity of the Mutant Enzyme Assessed by Proton NMR Spectroscopy, Pharmacogenetics 10, 439-451.
101. Mushiroda, T.; Douya, R.; Takahara, E. and Nagata, O. (2000) The Involvement of Flavin-Containing Monooxygenase but not CYP3A4 in Metabolism of Itopride Hydrochloride, a Gastroprokinetic Agent: Comparison with Cisapride and Mosapride Citrate. Drug Metab. Dispos. 28, 1231-1237.
102. Nikbakht, K. N.; Lawton, M. P. and Philpot, R. M. (1992) Guinea Pig or Rabbit Lung Flavin-Containing Monooxygenases with Distinct Mobilities in SDS-PAGE Are Allelic Variants That Differ at Only Two Positions. Pharmacogenetics 2, 207-216.
103. Ohmi, N.; Yoshida, H.; Endo, H.; Hasegawa, M.; Akimoto, M. and Higuchi, S. (2003) S-Oxidation of S-Methyl-Esonarimod by Flavin-Containing Monooxygenases in Human Liver Microsomes. Xenobiotica 33, 1221-1231.
104. Ohmiya, Y. and Mehendale, H. M. (1982) Metabolism of Chlorpromazine by Pulmonary Microsonial Enzymes in the Rat and Rabbit. Biochem. Pharmacol. 31, 157-162.
105. Overby, L. H.; Buckpitt, A. R.; Lawton, M. P.; Atta-Asafo-Adjei, E.; Schulze, J. and Philpot, R. M. (1995) Characterization of Flavin-Containing Monooxygenase 5 (FM05) Cloned from Human and Guinea Pig: Evidence That the Unique Catalytic Properties of FMO5 Are Not Confined to the Rabbit Ortholog. Arch. Biochem. Biophys. 317, 275-284.
106. Overby, L. H.; Carver, G. C. and Philpot, R. M. (1997) Quantitation and Kinetic Properties of Hepatic Microsomal and Recombinant Flavin-Containing Monooxygenases 3 and 5 from Humans. Chem. Biol. Interact. 106, 29-45.
107. Park, C. S., Chung, W. G.; Kang, J. H.; Roh, H. K.; Lee, K. H. and Cha, Y. N. (1999) Phenotyping of Flavin-Containing Monooxygenase Using Caffeine Metabolism and Genotyping of FMO3 Gene in a Korean Population. Pharmacogenetics 9, 155-164.
108. Park, C. S.; Kang, J. H.; Chung, W. G.; Yi, H. G.; Pie, J. E.; Park, D. K.; Hines, R. N.; McCarver, D. G. and Cha, Y. N. (2002) Ethnic Differences in Allelic Frequency of Two Flavin-Containing Monooxygenase 3 (FMO3) Polymorphisms: Linkage and Effects on in Vivo and in Vitro FMO Activities. Pharmacogenetics 12, 77-80.
109. Park, S. B.; Jacob, P.; Benowitz, N. L. and Cashman, J. R. (1993) Stereoselective Metabolism of (S)-(-)-Nicotine in Humans: Formation of Trans-(S)-(-)-Nicotine N-1′-Oxide. Chem. Res. Toxicol. 6, 880-888.
110. Parte, P. and Kupfer, D. (2005) Oxidation of Tamoxifen by Human Flavin-Containing Monooxygenase (FMO) 1 and FMO3 to Tamoxifen-N-Oxide and Its Novel Reduction Back to Tamoxifen by Human Cytochromes P450 and Hemoglobin. Drug Metab. Dispos. 33, 1446-1452.
111. Phillips, I. R. and Shephard, E. A. (2007) Trimethylaminuria. In: GeneReviews at GeneTests: Medical Genetics Information Resource (database online). Copyright, University of Washington, Seattle. 1997-2007. Available at http://www.genetests.org.
112. Phillips, I. R.; Dolphin, C. T.; Clair, P.; Hadley, M. R.; Hutt, A. J.; McCombie, R. R.; Smith, R. L. and Shephard, E. A. (1995) The Molecular Biology of the Flavin-Containing Monooxygenases of Man. Chem. Biol. Interact. 96, 17-32.
113. Pichard-Garcia, L.; Weaver, R. J.; Eckett; N.; Scarfe, G.; Fabre, J. M.; Lucas, C. and Maurel, P. (2004) The Olivacine Derivative S 16020 (9-Hydroxy-5, 6-Dimethyl-N-[2-(Dimethylamino)Ethyl)-6h-Pyrido(4, 3-B)-Carbaz Ole-1-Carboxamide) Induces CYP1A and Its Own Metabolism in Human Hepatocytes, in Primary Culture. Drug Metab. Dispos. 32, 80-98.
114. Poulsen, L. L.; Taylor, K.; Williams, D. E.; Masters, B. S. and Ziegler, D. M. (1986) Substrate Specificity of the Rabbit Lung Flavin-Containing Monooxygenase for Amines: Oxidation Products of Primary Alkylamines. Mol. Pharmacol. 30, 680-685.
115. Preti, G.; Ubriani, R.; Kim, J.; Lawley, H.; Tjoa, S.; Fennessey, P. and Fakharzadeh, S. (2002) Identification of a Novel R223Q Missense Mutation in the Flavin-Containing Monooxygenase 3 Gene in Trimethylaminuria. J. Invest. Dermatol. 119, 218.
116. Prough, R. A.; Freeman, P. C. and Hines, R. N. (1981) The Oxidation of Hydrazine Derivatives Catalyzed by the Purified Microsomal FAD-Containing Monooxygenase. J. Biol. Chem., 256, 4178-4184.
117. Qian, L. and Ortiz de Montellano, P. R. (2006) Oxidative Activation of Thiacetazone by the Mycobacterium Tuberculosis Flavin Monooxygenase EtaA and Human FM01 and FM03. Chem. Res. Toxicol. 19, 443-449.
118. Rae, J. M.; Johnson, M. D.; Lippman, M. E. and Flockhart, D. A. (2001) Rifampin Is a Selective, Pleiotropic Inducer of Drug Metabolism Genes in Human Hepatocytes: Studies with cDNA and Oligonucleotide Expression Arrays. J. Pharmacol. Exp. Ther. 299, 849-857.
119. Reid, J. M.; Walker, D. L.; Miller, J. K.; Benson, L. M.; Tomlinson, A. J.; Naylor, S.; Blajeski, A. L.; LoRusso, P. M. and Ames, M. M. (2004) The Metabolism of Pyrazoloacridine (NSC 366140) by Cytochromes P450 and Flavin Monooxygenase in Human Liver Microsomes. Clin. Cancer Res. 10, 1471-1480.
120. Rettie, A. E.; Lawton, M. P.; Sadeque, A. J.; Meier, G. P. and Philpot, R. M. (1994) Prochiral Sulfoxidation as a Probo for Multiple Forms of the Microsomal Flavin-Containing Monooxygenase: Studies with Rabbit FMO1, FMO2, FMO3, and FMO5 Expressed in Escherichia coli. Arch. Biochem. Biophys. 311, 369-377.
121. Ring, B. J.; Wrighton, S. A.; Aldridge, S. L.; Hansen, K.; Haehner, B. and Shipley, L. A. (1999) Flavin-Containing Monooxygenase-Mediated N-Oxidation of the M(1)-Muscarinic Agonist Xanomeline. Drug Metab. Dispos. 27, 1099-1103.
122. Ripp, S. L.; Itagaki, K.; Philpot, R. M. and Elfarra, A. A. (1999) Methionine S-oxidation in Human and Rabbit Liver Microsomes: Evidence for a High-affinity Methionine S-Oxidase Activity that is Distinct from Flavin-containing Monooxygenase 3. Arch. Biochem. Biophys. 367, 322-332.
123. Rodriguez, R. J. and Miranda, C. L. (2000) Isoforin Specificity of N-Deacetyl Ketoconazole by Human and Rabbit Flavin-Containing Monooxygenases. Drug Metab. Dispos. 28, 1083-1086.
124. Ruse, M. J. and Waring, R. H. (1991a) The Effect of Methimazole on Thioamide Bioactivation and Toxicity. Toxicol. Lett. 58, 37-41.
125. Ruse, M. J. and Waring, R. H. (1991b) The S-oxidation of Thioamides in Rat Liver Microsomes. Biochem. Soc. Trans. 19, 233S.
126. Sachse, C.; Ruschen, S.; Dettling, M.; Schley, J.; Bauer, S.; Muller-Oerlinghausen, B.; Roots, I. and Brockmoller, J. (1999) Flavin Monooxygenase 3 (FMO3) Polymorphism in a White Population: Allele Frequencies, Mutation Linkage, and Functional Effects on Clozapine and Caffeine Metabolism. Clin. Pharmacol. Ther. 66, 431-438.
127. Shephard, E. A.; Dolphin, C. T.; Fox, M. F,; Povey, S.; Smith, R. and Phillips, I. R. (1993) Localization of Genes Encoding Three Distinct Flavin-Containing Monooxygenases to Human Chromosome 1q. Genomics 16, 85-89.
128. Shephard, E. A.; Chandan, P.; Stevanovic-Walker, M.; Edwards, M. and Phillips, I. R. (2007) Alternative Promoters and Repetitive DNA Elements Define the Species-dependent Tissue-specific Expression of the FMO1 Genes of Human and Mouse. Biochem. J. 406, 491-499.
129. Shibutani, S.; Suzuki, N.; Laxmi, Y. R.; Schild, L. J.; Divi, R. L.; Grollman, A. P. and Poirier, M. C. (2003) Identification of Tamoxifen-DNA Adducts in Monkeys Treated with Tamoxifen. Cancer Res. 63, 4402-4406.
130. Shimada, T.; Yamiazaki, H.; Mimura, M.; Inui, Y. and Guengerich, F. P. (1994) Interindividual Variations in Human Liver Cytochrome P450 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, 414-423.
131. Shimizu, M.; Fujita, H.; Aoyama, T. and Yamazaki, H. (2006) Three Novel Single Nucleotide Polymorphisms of the FMO3 Gene in a Japanese Population. Drug Metab. Pharmacokinet. 21, 245-247.
132. Shimizu, M.; Cashman, J. R. and Yamazaki, H. (2007a) Transient Trimethylaminuria Related to Menstruation. BMC Med. Genet. 8, 2.
133. Shimizu, M.; Yano, H.; Nagashima, S.; Murayama, N.; Zhang, J.; Cashman, J. R. and Yamazaki, H. (2007b) Effect of Genetic Variants of the Human Flavin-Containing Monooxygenase 3 on N- and S- Oxygenation Activities. Drug Metab. Dispos. 35, 328-330.
134. Shimizu, M.; Tomioka, S.; Murayama, N. and Yamazaki, H. (2007c) Missense and Nonsense Mutations of the Flavin-Containing Monooxy-genase 3 Gene in a Japanese Cohort. Drug Metab. Pharmacokinet. 22, 61-64.
135. Smyser, B. P. and Hodgson, E. (1985) Metabolism of Phosphorous-Containing Compounds by Pig Liver Microsomal FAD-Containing Monooxgenase. Biochem. Pharmacol. 34, 1145-1150.
136. Stevens, J. C.; Melton, R. J.; Zaya, M. J. and Engel, L. C. (2003) Expression and Characterization of Functional Dog Flavin-Containing Monooxygenase 1. Mol. Pharmacol. 63, 271-275.
137. Stormer, E.; Roots, I. and Brockmoller, J. (2000) Benzydamine N-Oxidation as an Index Reaction Reflecting FMO Activity in Human Liver Microsomes and Impact of FMO3 Polymorphisms on Enzyme Activity [in Process Citation]. Br. J. Clin. Pharmacol. 50, 553-561.
138. Szoko, E.; Tabi, T.; Borbas, T.; Dalmadi, B.; Tihanyi, K. and Magyar, K. (2004) Assessment of the N-Oxidation of Deprenyl, Methamphetamine, and Amphetamine Enantiomers by Chiral Capillary Electrophoresis: An in Vitro Metabolism Study. Electrophoresis 25, 2866-2875.
139. Takamura, T.; Sakurai, M.; Ota, T.; Ando, H.; Honda, M. and Kaneko, S. (2004) Genes for Systemic Vascular Complications Are Differentially Expressed in the Livers of Type 2 Diabetic Patients. Diabetologia 47, 638-647.
140. Teresa, E.; Lonardo, F.; Fiumara, A.; Lombardi, C.; Russo, P.; Zuppi, C.; Scarano, G.; Musumeci, S. and Gianfrancesco, F. (2006) A Spectrum of Molecular Variation in a Cohort of Italian Families with Trimethylaminuria: Identification of Three Novel Mutations of the FMO3 Gene. Mol. Genet. Metab. 88, 192-195.
141. Tijet, N.; Boutros, P. C.; Moffat I. D.; Okey, A. B.; Tuomisto, J. and Pohjanvirta, R. (2006) Aryl Hydrocarbon Receptor Regulates Distinct Dioxin-Dependent and Dioxin-Independent Gene Batteries. Mol. Pharmacol. 69, 140-153.
142. Treacy, E. P.; Akerman, B. R.; Chow, L. M. L.; Youil, R.; Bibeau, C.; Lin, J.; Bruce, A. G.; Knight M.; Danks, D. M.; Cashman, J. R. and Forrest, S. M. (1998) Mutations of the Flavin-Containing Monooxygenase Gene (FMO3) Cause Trimethylaminuria, a Defect in Detoxication. Hum. Mol. Genet. 7, 839-845.
143. Tugnait, M.; Hawes, E. M.; McKay, G.; Rettie, A. E.; Haining, R. L. and Midha, K. K. (1997) N-Oxygenation of Clozapine by Flavin-Containing Monooxygenase. Drug Metab. Dispos. 25, 524-527.
144. Tynes, R. E.; Sabourin, P. J.; Hodgson, E. and Philpot, R. M. (1986) Formation of Hydrogen Peroxide and N-Hydroxylated Amines Catalyzed by Pulmonary Flavin-Containing Monooxygenases in the Presence of Primary Alkylamines. Arch. Biochem. Biophys. 251, 654-664.
145. Washio, T.; Kohsaka, K.; Arisawa, H. and Masunaga, H. (2003) Pharmacokinetics and Metabolism of the Novel Muscarinic Receptor Agonist Sni-2011 in Rats and Dogs. Arzneimitte/forschung 53, 26-33.
146. Whetstine, J. R.; Yueh, M.; McCarver, D. G.; Williams, D. E.; Park, C.; Kang, J. H.; Cha, Y.; Dolphin, C. T.; Shephard, E. A.; Phillips, I. R. and Hines, R. N. (2000) Ethnic Differences in Human Flavin-Containing Monooxygenase 2 (FMO2) Polymorphisms: Detection of Expressed Protein in African-Americans. Toxicol. Appl. Pharmacol. 168, 216-224.
147. Wierenga, R. K.; De Maeyer, M. C. H. and Hol, W. G. J. (1985) Interactions of Pyrophospate Moieties with α-Helixes in Dinucleotide Binding Proteins. Biochemistry 24, 1346-1357.
148. Williams, D. E.; Ziegler, D. M.; Nordin, D. J.; Hale, S. E. and Masters, B. S. (1984) Rabbit Lung Flavin-Containing Monooxygenase Is Immunochemically and Catalytically Distinct from the Liver Enzyme. Biochem. Biophys. Res. Commun. 125, 116-122.
149. Yamazaki, H.; Fujieda, M.; Togashi, M.; Saito, T.; Preti, G.; Cashman, J. R. and Kamataki, T. (2004) Effects of the Dietary Supplements, Activated Charcoal and Copper Chlorophyllin, on Urinary Excretion of Trimethylamine in Japanese Trimethylaminuria Patients. Life Sci. 74, 2739-2747.
150. Yamazaki, H.; Fujita, H.; Gunji, T.; Zhang, J.; Kamataki, T.; Cashman, J. R. and Shimizu, M. (2007) Stop Codon Mutations in the Flavin-Containing Monooxygenase, 3 (FMO3) Gene Responsible for Trimethylaminuria. in a Japanese Population. Mol. Genet. Metab. 90, 58-63.
151. Yeung, C. K.; Lang, D. H.; Thummel, K. E. and Rettie, A. E. (2000) Immunoquantitation of FMO1 in Human Liver, Kidney, and Intestine. Drug Metab. Dispos. 28, 1107-1111.
152. Yueh, M. F.; Krueger, S. K. and Williams, D. E. (1997) Pulmonary Flavin-Containing Monooxygenase (FMO) in Rhesus Macaque: Expression of FMO2 Protein, mRNA and Analysis of the cDNA. Biochim. Biophys. Acta 1350, 267-271.
153. Zhang, A. Q.; Mitchell, S. C. and Smith, R. L. (1996) Exacerbation of Symptoms of Fish-Odour Syndrome During Menstruation. Lancet 348, 1740-1741.
154. Zhang, J. and Cashman, J. R. (2006) Quantitative Analysis of FMO Gene mRNA Levels in Human Tissues. Drug Metab. Dispos. 34, 19-26.
155. Zhang, J.; Tran, Q.; Lattard, V. and Cashman, J. R. (2003) Deleterious Mutations in the Flavin-Containing Monooxygenase 3 (FMO3) Gene Causing Trimethylaminuria. Pharmacogenetics 13, 495-500.
156. Ziegler,D. M. (1980) Microsomal Flavin-Containing Monooxygenase: Oxygenation of Nucleophilic Nitrogen and Sulfur Compounds. In Enzymatic Basis of Detoxication; Jakoby, W. B., Ed.; Academic Press: New York, pp. 201-277.
157. Ziegler, D. M. (1991) The 1990 Bernard B. Brodie Award Lecture. Unique Properties of the Enzymes of Detoxication. Drug Metab. Dispos. 19, 847-852.
158. Ziegler, D. M. (1993) Recent Studies on the Structure and Function of Multisubstrate Flavin-Containing Monooxygenases. Annu. Rev. Pharmacol. Toxicol. 33, 179-199.
159. Ziegler, D. M.; Poulsen, L. L. and McKee, E. M. (1971) Interaction of Primary Amines with a Mixed-Function Amine Oxidase Isolated from Pig Liver Microsomes. Xenobiotica 1, 523-531.
160. Ziegler, D. M.; Graf, P.; Poulsen, L. L.; Stahl, W. and Sies, H. (1992) Nadph-Dependent Oxidation of Reduced Ebselen, 2-Selenylbenzanilide, and of 2-(Methylseleno)Benzanilide Catalyzed by Pig Liver Flavin-Containing Monooxygenase. Chem. Res. Toxicol. 5, 163-166.
161. Ziegler-Skylakakis, K.; Nill, S.; Pan, J. F. and Andrae, U. (1998) S-Oxygenation of Thiourea Results in the Formation of Genotoxic Products. Environ. Mol. Mutagen 31, 362-373.
162. Zschocke, J.; Kohlmueller, D.; Quak, E.; Meissner, T.; Hoffmann, G. F. and Mayatepek, E. (1999) Mild Trimethylaminuria Caused by Common Variants in FMO3 Gene. Lancet 354, 834-835.