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Gene Review

Fmo1  -  flavin containing monooxygenase 1

Mus musculus

Synonyms: Dimethylaniline oxidase 1, FMO 1, Fmo-1, Hepatic flavin-containing monooxygenase 1
 
 
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Disease relevance of Fmo1

 

High impact information on Fmo1

  • OBJECTIVES: To date, six flavin-containing monooxygenase (FMO) genes have been identified in humans, FMOs 1, 2, 3, 4 and 6, which are located within a cluster on chromosome 1, and FMO5, which is located outside the cluster [3].
  • The objectives were to review and update current knowledge of the structure and expression profiles of these genes and of their mouse counterparts and to determine, via a bioinformatics approach, whether other FMO genes are present in the human and mouse genomes [3].
  • Organization and evolution of the flavin-containing monooxygenase genes of human and mouse: identification of novel gene and pseudogene clusters [3].
  • In addition, we describe a novel human FMO gene cluster on chromosome 1, located 4 Mb telomeric of the original cluster [3].
  • RNase protection assays showed that the most abundant isoform in newborn liver, lung, kidney and brain, and in adult lung and kidney is FMO1, but in adult liver FMO5 is present in greatest amounts [4].
 

Biological context of Fmo1

 

Anatomical context of Fmo1

 

Associations of Fmo1 with chemical compounds

  • In addition, testosterone administration to females (sexually intact and gonadectomized animals) reduced FMO1 expression and obviated FMO3 expression [10].
  • Interestingly, FMO1 protein levels were increased in sexually intact males following treatment with 17 beta-estradiol; however, only a slight increase in FMO3 protein level was observed [10].
  • The Km value for tamoxifen is 1.2 mM for mouse FMO1 (human FMO1 is not expressed in adults) and 1.4 mM for human FMO3, with no detectable activity being expressed toward tamoxifen by FMO5 from either mouse or human [11].
  • Molecular cloning of mouse liver flavin containing monooxygenase (FMO1) cDNA and characterization of the expression product: metabolism of the neurotoxin, 1,2,3,4-tetrahydroisoquinoline (TIQ) [12].
  • The expressed FMO1 protein showed activity toward methimazole, and FMO5 was active toward noctylamine [1].
 

Other interactions of Fmo1

 

Analytical, diagnostic and therapeutic context of Fmo1

References

  1. Molecular cloning, sequence, and expression of mouse flavin-containing monooxygenases 1 and 5 (FMO1 and FMO5). Cherrington, N.J., Falls, J.G., Rose, R.L., Clements, K.M., Philpot, R.M., Levi, P.E., Hodgson, E. J. Biochem. Mol. Toxicol. (1998) [Pubmed]
  2. Evidence for the involvement of N-methylthiourea, a ring cleavage metabolite, in the hepatotoxicity of methimazole in glutathione-depleted mice: structure-toxicity and metabolic studies. Mizutani, T., Yoshida, K., Murakami, M., Shirai, M., Kawazoe, S. Chem. Res. Toxicol. (2000) [Pubmed]
  3. Organization and evolution of the flavin-containing monooxygenase genes of human and mouse: identification of novel gene and pseudogene clusters. Hernandez, D., Janmohamed, A., Chandan, P., Phillips, I.R., Shephard, E.A. Pharmacogenetics (2004) [Pubmed]
  4. Cell-, tissue-, sex- and developmental stage-specific expression of mouse flavin-containing monooxygenases (Fmos). Janmohamed, A., Hernandez, D., Phillips, I.R., Shephard, E.A. Biochem. Pharmacol. (2004) [Pubmed]
  5. Physiological factors affecting protein expression of flavin-containing monooxygenases 1, 3 and 5. Cherrington, N.J., Cao, Y., Cherrington, J.W., Rose, R.L., Hodgson, E. Xenobiotica (1998) [Pubmed]
  6. Gender differences in hepatic expression of flavin-containing monooxygenase isoforms (FMO1, FMO3, and FMO5) in mice. Falls, J.G., Blake, B.L., Cao, Y., Levi, P.E., Hodgson, E. J. Biochem. Toxicol. (1995) [Pubmed]
  7. Quantitative analysis of FMO gene mRNA levels in human tissues. Zhang, J., Cashman, J.R. Drug Metab. Dispos. (2006) [Pubmed]
  8. Effects of N-methylmercaptoimidazole on the disposition of MPTP and its metabolites in mice. Chiba, K., Horii, H., Kubota, E., Ishizaki, T., Kato, Y. Eur. J. Pharmacol. (1990) [Pubmed]
  9. Purification of the flavin-containing monooxygenase from mouse and pig liver microsomes. Sabourin, P.J., Smyser, B.P., Hodgson, E. Int. J. Biochem. (1984) [Pubmed]
  10. Regulation of mouse liver flavin-containing monooxygenases 1 and 3 by sex steroids. Falls, J.G., Ryu, D.Y., Cao, Y., Levi, P.E., Hodgson, E. Arch. Biochem. Biophys. (1997) [Pubmed]
  11. Flavin-containing monooxygenase isoform specificity for the N-oxidation of tamoxifen determined by product measurement and NADPH oxidation. Hodgson, E., Rose, R.L., Cao, Y., Dehal, S.S., Kupfer, D. J. Biochem. Mol. Toxicol. (2000) [Pubmed]
  12. Molecular cloning of mouse liver flavin containing monooxygenase (FMO1) cDNA and characterization of the expression product: metabolism of the neurotoxin, 1,2,3,4-tetrahydroisoquinoline (TIQ). Itoh, K., Nakamura, K., Kimura, T., Itoh, S., Kamataki, T. The Journal of toxicological sciences. (1997) [Pubmed]
  13. Characterization of hepatic microsomal metabolism as an in vivo detoxication pathway of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine in mice. Chiba, K., Kubota, E., Miyakawa, T., Kato, Y., Ishizaki, T. J. Pharmacol. Exp. Ther. (1988) [Pubmed]
  14. Polyamine effects on cytochrome P-450- and flavin-containing monooxygenase-mediated oxidation of xenobiotics. Osimitz, T.G., Kulkarni, A.P. Drug Metab. Dispos. (1985) [Pubmed]
  15. Spectrophotometric assay of the flavin-containing monooxygenase and changes in its activity in female mouse liver with nutritional and diurnal conditions. Dixit, A., Roche, T.E. Arch. Biochem. Biophys. (1984) [Pubmed]
  16. Role of metabolism by flavin-containing monooxygenase in thioacetamide-induced immunosuppression. Lee, J.W., Shin, K.D., Lee, M., Kim, E.J., Han, S.S., Han, M.Y., Ha, H., Jeong, T.C., Koh, W.S. Toxicol. Lett. (2003) [Pubmed]
 
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