A mutation in the flavin-containing monooxygenase 3 gene and its effects on catalytic activity for N-oxidation of trimethylamine in vitro.
To clarify the mutation of the flavin-containing monooxygenase (FMO) 3 gene causing fish-odor syndrome, we analyzed the FMO3 gene of a Thai subject who possibly suffered from fish-odor syndrome. A novel mutation, a single-base substitution from G to A at the position of 265 (G265A), was identified in exon 3. The mutation caused an amino acid substitution from valine to isoleucine at residue 58 (V58I). The mutated FMO3 protein with V58I exhibited the reduced trimethylamine N-oxidase activity when it was expressed in E. coli. The V(max)/K(m) value for the activity of the mutant-type FMO3 was about 5 times lower than that for the wild-type FMO3.
Kubota
Megumi
M
Laboratory of Drug Metabolism, Division of Pharmacobio-dynamics, Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan.
Nakamoto
Yoko
Y
Nakayama
Kazuo
K
Ujjin
Pailin
P
Satarug
Soisungwan
S
Mushiroda
Taisei
T
Yokoi
Tsuyoshi
T
Funayama
Masato
M
Kamataki
Tetsuya
T