In vitro and in vivo N-oxygenation of trimethylamine (TMA) in the suncus (S
uncus murinus) was investigated. The N-oxygenation of TMA has been thought
to be catalyzed by flavin-containing monooxygenase (FMO). In a previous stu
dy, we found that the levels of mRNAs for FMOs were extremely low in the su
ncus. Thus, we intended to evaluate the capacity of the suncus to N-oxygena
te TMA compared to the rat. Eadie-Hofstee plots of the TMA N-oxygenation by
suncus liver microsomes showed a biphasic pattern, suggesting that more th
an two enzymes were involved in this reaction. The low K-m component in the
suncus showed a twofold higher K-m (55 vs. 31 mu M) and a fourfold lower V
-max (0.61 vs 2.5 nmol/min/mg protein) values than those obtained using rat
Liver microsomes, resulting in a sevenfold lower V-max/K-m (11 vs 82 mu l/
min/mg protein) value. After an intraperitoneal administration of TMA (10 m
g/kg body wt), the suncus excreted 39.6% of the dose in 24-h urine as TMA,
whereas the rats excreted 6.3%. Metabolic ratio in the TMA N-oxygenation wa
s 1.42 and 0.11 in the suncus and the rat, respectively. These results indi
cate that the suncus can be an animal model for a poor metabolizer phenotyp
e in TMA metabolism. (C) 2000 Academic Press.