Flavin-containing monooxygenase

Flavin-containing monooxygenase
Flavin-containing monooxygenase FMO
Symbol Flavin_mOase
Pfam PF00743
InterPro IPR000960

The flavin-containing monooxygenase (FMO) protein family consists of a group of enzymes that catalyze chemical reactions via the bound cofactor flavin. These reactions involve oxidation of heteroatoms, particularly nucleophilic atoms such as the nitrogen of amines.[1]

These enzymes metabolise xenobiotics[2]. Using an NADPH cofactor and FAD prosthetic group, these microsomal proteins catalyse the oxygenation of nucleophilic nitrogen, sulphur, phosphorus and selenium atoms in a range of structurally diverse compounds. FMOs have been implicated in the metabolism of a number of pharmaceuticals, pesticides and toxicants. In man, lack of hepatic FMO-catalysed trimethylamine metabolism results in trimethylaminuria (fish odour syndrome). Five mammalian forms of FMO are now known and have been designated FMO1-FMO5[3][4][5][6][7].

The best-known such protein is called FMO3 and is mutated in the vast majority of cases of trimethylaminuria, a genetic disease that causes deficiencies in breakdown of trimethylamine and gives the patient a fishy body odor.[8] In yeast, FMO proteins are associated with redox cycling of glutathione to glutathione disulfide, a system that maintains the redox state of the cell and heavily influences the protein folding rates of disulfide bond-containing proteins.[9]



  1. ^ Cashman JR (1995). "Structural and catalytic properties of the mammalian flavin-containing monooxygenase". Chem Res Toxicol 8 (2): 166–81. PMID 7766799. 
  2. ^ Lawton MP, Cashman JR, Cresteil T, Dolphin CT, Elfarra AA, Hines RN, Hodgson E, Kimura T, Ozols J, Phillips IR (1994). "A nomenclature for the mammalian flavin-containing monooxygenase gene family based on amino acid sequence identities". Arch. Biochem. Biophys. 308 (1): 254–257. doi:10.1006/abbi.1994.1035. PMID 8311461. 
  3. ^ Phillips IR, Shephard EA, Ziegler DM, Povey S, Smith RL, Ayesh R, Dolphin C, Palmer CN (1991). "Cloning, primary sequence, and chromosomal mapping of a human flavin-containing monooxygenase (FMO1)". J. Biol. Chem. 266 (19): 12379–12385. PMID 1712018. 
  4. ^ Lawton MP, Hodgson E, Philpot RM, Gasser R, Tynes RE (1990). "The flavin-containing monooxygenase enzymes expressed in rabbit liver and lung are products of related but distinctly different genes". J. Biol. Chem. 265 (10): 5855–5861. PMID 2318837. 
  5. ^ Cashman JR, Gu Q, Lomri N (1992). "Molecular cloning of the flavin-containing monooxygenase (form II) cDNA from adult human liver". Proc. Natl. Acad. Sci. U.S.A. 89 (5): 1685–1689. doi:10.1073/pnas.89.5.1685. PMC 48517. PMID 1542660. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=48517. 
  6. ^ Dolphin CT, Phillips IR, Shephard EA, Povey S, Smith RL (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. PMC 1133153. PMID 1417778. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1133153. 
  7. ^ Lawton MP, Philpot RM, Atta-Asafo-Adjei E (1993). "Cloning, sequencing, distribution, and expression in Escherichia coli of flavin-containing monooxygenase 1C1. Evidence for a third gene subfamily in rabbits". J. Biol. Chem. 268 (13): 9681–9689. PMID 8486656. 
  8. ^ Hernandez D, Addou S, Lee D, Orengo C, Shephard EA, Phillips IR (September 2003). "Trimethylaminuria and a humanFMO3 mutation database". Human Mutation 22 (3): 209–13. doi:10.1002/humu.10252. PMID 12938085. 
  9. ^ Suh JK, Poulsen LL, Ziegler DM, Robertus JD (1999). "Yeast flavin-containing monooxygenase generates oxidizing equivalents that control protein folding in the endoplasmic reticulum". Proc Natl Acad Sci 96 (6): 2687–91. doi:10.1073/pnas.96.6.2687. PMC 15830. PMID 10077572. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=15830. 

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