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首页> 外文期刊>Analytical and bioanalytical chemistry >Formation of methylated oxyarsenicals and thioarsenicals in wild-type and arsenic (+3 oxidation state) methyltransferase knockout mice exposed to arsenate
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Formation of methylated oxyarsenicals and thioarsenicals in wild-type and arsenic (+3 oxidation state) methyltransferase knockout mice exposed to arsenate

机译：在暴露于砷酸盐的野生型和砷（+3氧化态）甲基转移酶敲除小鼠中甲基化氧化砷和硫砷的形成

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Arsenic (+3 oxidation state) methyltransferase (As3mt) plays a central role in the enzymatically catalyzed conversion of inorganic arsenic into methylated metabolites. Most studies of the metabolism and disposition of arsenicals following exposure to inorganic arsenic focus on the formation and fate of methylated oxyarsenicals. However, recent research has shown methylated thioarsenicals to be another important class of metabolites of inorganic arsenic. Here, we report on the presence of methylated oxy- and thioarsenicals in urine and liver from wild-type mice that efficiently methylate inorganic arsenic and from As3mt knockout mice that lack arsenic methyltransferase activity. Following a single oral dose of 0.5 mg of arsenic as arsenate/kg body weight, urine from wild-type mice contained methylated oxyarsenicals and unknown arsenicals. Further analysis identified one unknown arsenical in urine of wild-type mice as dimethylmonothioarsinic acid. In addition, another unknown arsenical in urine of wild-type mice that occurred in the urine of about 20 % of arsenate-treated mice. The presence of low levels of methylated arsenicals in liver digests of As3mt knockout mice may reflect the activity of other methyltransferases or the absorption of methylated arsenicals formed by the microbiota of the gastrointestinal tract. The lack of methylated thioarsenicals in urine of As3mt knockout mice suggests a close link between the processes that form methylated oxy- and thioarsenicals.
机译：砷（+3氧化态）甲基转移酶（As3mt）在酶催化下将无机砷转化为甲基化代谢物发挥重要作用。接触无机砷后，有关砷的代谢和处置的大多数研究都集中在甲基化含氧砷的形成和命运上。但是，最近的研究表明，甲基化的硫代砷化物是另一类重要的无机砷代谢产物。在这里，我们报道了尿液和肝脏中甲基化的氧和硫代砷化物的存在，它们来自有效地使无机砷甲基化的野生型小鼠和缺乏砷甲基转移酶活性的As3mt基因敲除小鼠。在单次口服0.5 mg砷砷/ kg体重后，来自野生型小鼠的尿液中含有甲基化的氧化砷和未知的砷。进一步的分析确定了野生型小鼠尿液中一种未知的砷，为二甲基单硫代ar麻酸。此外，野生型小鼠尿液中的另一种未知砷，在大约20％的砷酸盐处理小鼠的尿液中出现。 As3mt基因敲除小鼠肝脏消化物中甲基化砷含量较低，可能反映了其他甲基转移酶的活性或胃肠道微生物形成的甲基化砷的吸收。 As3mt基因敲除小鼠尿液中甲基化硫代砷的缺乏表明了形成甲基化氧代和硫代砷的过程之间的紧密联系。

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