Flavin containing monooxygenase 1 explained

Dimethylaniline monooxygenase [N-oxide-forming] 1 is an enzyme that in humans is encoded by the FMO1 gene.^[1]

Metabolic N-oxidation of the diet-derived amino-trimethylamine (TMA) is mediated by flavin-containing monooxygenase and is subject to an inherited FMO3 polymorphism in humans resulting in a small subpopulation with reduced TMA N-oxidation capacity resulting in fish odor syndrome Trimethylaminuria. Three forms of the enzyme, FMO1 found in fetal liver, FMO2 found in adult liver, and FMO3 are encoded by genes clustered in the 1q23-q25 region. Flavin-containing monooxygenases are NADPH-dependent flavoenzymes that catalyzes the oxidation of soft nucleophilic heteroatom centers in xenobiotics such as pesticides and drugs.

Further reading

• Hines RN . The mammalian flavin-containing monooxygenases: molecular characterization and regulation of expression . Toxicol. Appl. Pharmacol. . 125 . 1 . 1–6 . 1994 . 8128486 . 10.1006/taap.1994.1042 . Cashman JR . Philpot RM . Williams . DE . Ziegler . DM .
• Cashman JR . The implications of polymorphisms in mammalian flavin-containing monooxygenases in drug discovery and development . Drug Discov. Today . 9 . 13 . 574–581 . 2004 . 15203093 . 10.1016/S1359-6446(04)03136-8 .
• Dolphin C . Cloning, primary sequence, and chromosomal mapping of a human flavin-containing monooxygenase (FMO1) . J. Biol. Chem. . 266 . 19 . 12379–85 . 1991 . 1712018 . Shephard EA . Povey S . Palmer . CN . Ziegler . DM . Ayesh . R . Smith . RL . Phillips . IR . 10.1016/S0021-9258(18)98908-8 . free .
• Phillips IR . The molecular biology of the flavin-containing monooxygenases of man . Chem. Biol. Interact. . 96 . 1 . 17–32 . 1995 . 7720101 . 10.1016/0009-2797(94)03580-2 . Dolphin CT . Clair P . Hadley . MR . Hutt . AJ . McCombie . RR . Smith . RL . Shephard . EA . 1995CBI....96...17P .
• Lawton MP . A nomenclature for the mammalian flavin-containing monooxygenase gene family based on amino acid sequence identities . Arch. Biochem. Biophys. . 308 . 1 . 254–257 . 1994 . 8311461 . 10.1006/abbi.1994.1035 . Cashman JR . Cresteil T . Dolphin . CT . Elfarra . AA . Hines . RN . Hodgson . E . Kimura . T . Ozols . J .
• Shephard EA . Localization of genes encoding three distinct flavin-containing monooxygenases to human chromosome 1q . Genomics . 16 . 1 . 85–89 . 1993 . 8486388 . 10.1006/geno.1993.1144 . Dolphin CT . Fox MF . Povey . S . Smith . R . Phillips . IR .
• Hay JC, Chao DS, Kuo CS, Scheller RH . Protein interactions regulating vesicle transport between the endoplasmic reticulum and Golgi apparatus in mammalian cells . Cell . 89 . 1 . 149–158 . 1997 . 9094723 . 10.1016/S0092-8674(00)80191-9 . 8682509 . free .
• Yeung CK, Lang DH, Thummel KE, Rettie AE . Immunoquantitation of FMO1 in human liver, kidney, and intestine . Drug Metab. Dispos. . 28 . 9 . 1107–11 . 2000 . 10950857 .
• Washio T, Arisawa H, Kohsaka K, Yasuda H . Identification of human drug-metabolizing enzymes involved in the metabolism of SNI-2011 . Biol. Pharm. Bull. . 24 . 11 . 1263–1266 . 2002 . 11725960 . 10.1248/bpb.24.1263 . free .
• Koukouritaki SB . Human hepatic flavin-containing monooxygenases 1 (FMO1) and 3 (FMO3) developmental expression . Pediatr. Res. . 51 . 2 . 236–243 . 2002 . 11809920 . 10.1203/00006450-200202000-00018 . Simpson P . Yeung CK . Rettie . Allan E. . Hines . Ronald N. . free.
• Strausberg RL . Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences . Proc. Natl. Acad. Sci. U.S.A. . 99 . 26 . 16899–16903 . 2003 . 12477932 . 10.1073/pnas.242603899 . 139241 . Feingold EA . Grouse LH . Derge . JG . Klausner . RD . Collins . FS . Wagner . L . Shenmen . CM . Schuler . GD . 2002PNAS...9916899M . free .
• Furnes B, Feng J, Sommer SS, Schlenk D . Identification of novel variants of the flavin-containing monooxygenase gene family in African Americans . Drug Metab. Dispos. . 31 . 2 . 187–193 . 2003 . 12527699 . 10.1124/dmd.31.2.187 . 6619389 .
• Attar M, Dong D, Ling KH, Tang-Liu DD . Cytochrome P450 2C8 and flavin-containing monooxygenases are involved in the metabolism of tazarotenic acid in humans . Drug Metab. Dispos. . 31 . 4 . 476–481 . 2003 . 12642475 . 10.1124/dmd.31.4.476 .
• Hines RN . Genetic variability at the human FMO1 locus: significance of a basal promoter yin yang 1 element polymorphism (FMO1*6) . J. Pharmacol. Exp. Ther. . 306 . 3 . 1210–1218 . 2003 . 12829732 . 10.1124/jpet.103.053686 . Luo Z . Hopp KA . Cabacungan . ET . Koukouritaki . SB . McCarver . DG . 25093628 .
• Ota T . Complete sequencing and characterization of 21,243 full-length human cDNAs . Nat. Genet. . 36 . 1 . 40–45 . 2004 . 14702039 . 10.1038/ng1285 . Suzuki Y . Nishikawa T . Otsuki . Tetsuji . Sugiyama . Tomoyasu . Irie . Ryotaro . Wakamatsu . Ai . Hayashi . Koji . Sato . Hiroyuki . free .
• Gerhard DS . The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC) . Genome Res. . 14 . 10B . 2121–2127 . 2004 . 15489334 . 10.1101/gr.2596504 . 528928 . Wagner L . Feingold EA . Shenmen . CM . Grouse . LH . Schuler . G . Klein . SL . Old . S . Rasooly . R .
• Zhang J, Cashman JR . Quantitative analysis of FMO gene mRNA levels in human tissues . Drug Metab. Dispos. . 34 . 1 . 19–26 . 2006 . 16183778 . 10.1124/dmd.105.006171 . 1784074 .
• Bartsch M . Salicylic acid-independent ENHANCED DISEASE SUSCEPTIBILITY1 signaling in Arabidopsis immunity and cell death is regulated by the monooxygenase FMO1 and the Nudix hydrolase NUDT7 . Plant Cell . 18 . 4 . 1038–1051 . 2006 . 16531493 . 10.1105/tpc.105.039982 . 1425861 . Gobbato E . Bednarek P . Debey . S . Schultze . JL . Bautor . J . Parker . JE .

Notes and References

1. Web site: Entrez Gene: FMO1 flavin containing monooxygenase 1.