Scientific background: |
FMO3(Flavin-containing Monooxygenase 3) is an enzyme that in humans is encoded by
the FMO3 gene. The mammalian flavin-containing monooxygenases (FMO) represent a multigene
family whose gene products are localized in the endoplasmic reticulum of many
tissues. The FMO3 gene contains 1 noncoding and 8 coding exons. The FMO3 gene is mapped on
1q24.3. Using quantitative RNase protection assays, FMO3 is present in low abundance in fetal liver
and lung and in adult kidney and lung, and in much greater abundance in adult liver. By Western blot
analysis of human liver microsomal samples ranging from 8 weeks gestation to 18 years of age, FMO1
is the major fetal isoform and FMO3 is the major adult isoform. FMO3 was expressed at intermediate
levels until 11 years of age when a gender-independent increase in FMO3 expression was observed
during puberty. Sufferers of trimethylaminuria may display a reduced ability to metabolize substrates
for FMO3 such as nicotine. FMO3 metabolizes a number of drugs, including amphetamine, clozapine,
deprenyl, metamphetamine, tamoxifen, ethionamide, thiacetazone, and sulindac sulfide. |
References: |
Akerman, B. R., Chow, L., Forrest, S., Youil, R., Cashman, J., Treacy, E. P. Mutations in the
flavin-containing monoxygenase (sic) form 3 (FMO3) gene cause trimethylaminuria, fish odour
syndrome. (Abstract) Am. J. Hum. Genet. 61 (suppl.): A53 only, 1997.
2. Cashman, J. R., Zhang, J. Interindividual differences of human flavin-containing monooxygenase 3:
genetic polymorphisms and functional variation. Drug Metab. Dispos. 30: 1043-1052, 2002.
3. Dolphin, C. T., Janmohamed, A., Smith, R. L., Shephard, E. A., Phillips, I. R. Missense mutation in
flavin-containing mono-oxygenase 3 gene, FMO3, underlies fish-odour syndrome. Nature Genet. 17:
491-494, 1997. |