The suncus (Suncus murinus) shows poor metabolic phenotype for trimethylamine N-oxygenation

In vitro and in vivo N-oxygenation of trimethylamine (TMA) in the suncus (Suncus murinus) was investigated. The N-oxygenation of TMA has been thought to be catalyzed by flavin-containing monooxygenase (FMO). In a previous study, we found that the levels of mRNAs for FMOs were extremely low in the suncus. Thus, we intended to evaluate the capacity of the suncus to N-oxygenate TMA compared to the rat. Eadie-Hofstee plots of the TMA N-oxygenation by suncus liver microsomes showed a biphasic pattern, suggesting that more than two enzymes were involved in this reaction. The low K(m) component in the suncus showed a twofold higher K(m) (55 vs. 31 microM) 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 microl/min/mg protein) value. After an intraperitoneal administration of TMA (10 mg/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 was 1.42 and 0.11 in the suncus and the rat, respectively. These results indicate that the suncus can be an animal model for a poor metabolizer phenotype in TMA metabolism.