FMO4 explained

Dimethylaniline monooxygenase [N-oxide-forming] 4 is an enzyme that in humans is encoded by the FMO4 gene.^{[1] [2]}

Function

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 man 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 drugs, pesticides, and xenobiotics.

Cancer

FMO4 gene has been observed progressively downregulated in Human papillomavirus-positive neoplastic keratinocytes derived from uterine cervical preneoplastic lesions at different levels of malignancy. ^[3] For this reason, FMO4 is likely to be associated with tumorigenesis and may be a potential prognostic marker for uterine cervical preneoplastic lesions progression. ^[4]

Further reading

• Hines RN, Cashman JR, Philpot RM, Williams DE, Ziegler DM . 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 .
• Dolphin CT, Shephard EA, Povey S, Smith RL, Phillips IR . Cloning, primary sequence and chromosomal localization of human FMO2, a new member of the flavin-containing mono-oxygenase family . Biochem. J. . 287 (Pt 1) . Pt 1 . 261–7 . 1992 . 10.1042/bj2870261 . 1417778 . 1133153 .
• Phillips IR, Dolphin CT, Clair P, Hadley MR, Hutt AJ, McCombie RR, Smith RL, Shephard EA . 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 . 1995CBI....96...17P .
• Itagaki K, Carver GT, Philpot RM . Expression and characterization of a modified flavin-containing monooxygenase 4 from humans . J. Biol. Chem. . 271 . 33 . 20102–7 . 1996 . 8702731 . 10.1074/jbc.271.33.20102 . free .
• Janmohamed A, Dolphin CT, Phillips IR, Shephard EA . Quantification and cellular localization of expression in human skin of genes encoding flavin-containing monooxygenases and cytochromes P450 . Biochem. Pharmacol. . 62 . 6 . 777–86 . 2001 . 11551524 . 10.1016/S0006-2952(01)00718-3 .
• 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 . 187–93 . 2003 . 12527699 . 10.1124/dmd.31.2.187 . 6619389 .

Notes and References

1. Lawton MP, Cashman JR, Cresteil T, Dolphin CT, Elfarra AA, Hines RN, Hodgson E, Kimura T, Ozols J, Phillips IR . A nomenclature for the mammalian flavin-containing monooxygenase gene family based on amino acid sequence identities . Arch Biochem Biophys . 308 . 1 . 254–7 . Mar 1994 . 8311461 . 10.1006/abbi.1994.1035 .
2. Web site: Entrez Gene: FMO4 flavin containing monooxygenase 4.
3. Rotondo JC, Bosi S, Bassi C, Ferracin M, Lanza G, Gafà R, Magri E, Selvatici R, Torresani S, Marci R, Garutti P, Negrini M, Tognon M, Martini F . Gene expression changes in progression of cervical neoplasia revealed by microarray analysis of cervical neoplastic keratinocytes. . J Cell Physiol . 230. 4 . 802–812 . April 2015 . 25205602 . 10.1002/jcp.24808 . 11392/2066612 . 24986454 . free .
4. Rotondo JC, Bosi S, Bassi C, Ferracin M, Lanza G, Gafà R, Magri E, Selvatici R, Torresani S, Marci R, Garutti P, Negrini M, Tognon M, Martini F . Gene expression changes in progression of cervical neoplasia revealed by microarray analysis of cervical neoplastic keratinocytes. . J Cell Physiol . 230. 4 . 802–812 . April 2015 . 25205602 . 10.1002/jcp.24808 . 11392/2066612 . 24986454 . free .