Lee P W, Neal R A
Drug Metab Dispos. 1978 Sep-Oct;6(5):591-600.
The incubation of methimazole (1-methyl-2-thioimidazole, MMI) with rat hepatic microsomes led to the formation of 3-methyl-2-thiohydantoin and N-methylimidazole. In addition, an NADPH-stimulated binding of 14C and 35S from [14C]- and [35s]MMI to microsomal macromolecules was seen. Both the NADPH-stimulated N-methylimidazole formation and binding of radioactivity from [14C]- and [35S]MMI to microsomal macromolecules appeared to be catalyzed largely by the cytocrhome P-450 to monoxygenase systems of rat hepatic microsomes. A portion of the radioactivity bound to microsomes incubated with [14C]- and [35S]MMI was released as unchanged MMI on prolonged incubation under acid conditions; this suggests that strong binding of MMI to microsomes occurred. A portion of the 35S bound to microsomes incubated with [35S]MMI can be released as 35SCN- on incubation of the 35S-labeled microsomes with CN-. These data suggest that a portion of the sulfur released in the metabolism of MMI to N-methylimidazole is in the form of atomic sulfur (S), which binds to cysteine sulfhydryl groups (R-S-H) in microsomal proteins to form a hydrodisulfide (R-S-S-H).
甲巯咪唑（1-甲基-2-硫代咪唑，MMI）与大鼠肝脏微粒体孵育会生成3-甲基-2-硫代乙内酰脲和N-甲基咪唑。此外，还观察到NADPH刺激下，[14C]-和[35S]MMI中的14C和35S与微粒体大分子结合。NADPH刺激下N-甲基咪唑的形成以及[14C]-和[35S]MMI的放射性与微粒体大分子的结合，似乎主要由大鼠肝脏微粒体的细胞色素P-450单加氧酶系统催化。在酸性条件下长时间孵育后，与[14C]-和[35S]MMI孵育的微粒体结合的一部分放射性以未变化的MMI形式释放；这表明MMI与微粒体发生了强烈结合。与[35S]MMI孵育的微粒体结合的一部分35S在35S标记的微粒体与CN-孵育时可作为35SCN-释放。这些数据表明，MMI代谢为N-甲基咪唑过程中释放的一部分硫是以原子硫（S）的形式存在，它与微粒体蛋白中的半胱氨酸巯基（R-S-H）结合形成二硫氢化物（R-S-S-H）。
