Research Center for Medical Glycoscience, National Institute of Advanced Industrial Science and Technology, Central 6, 1-1-1 Higashi, Tsukuba, Ibaraki 305-8566, Japan.
Research Center for Medical Glycoscience, National Institute of Advanced Industrial Science and Technology, Central 6, 1-1-1 Higashi, Tsukuba, Ibaraki 305-8566, Japan.
J Biol Chem. 2012 Mar 23;287(13):10032-10038. doi: 10.1074/jbc.M111.324244. Epub 2012 Feb 6.
Although selenium is an essential element, its excessive uptake is detrimental to living organisms. The significance of selenium for living organisms has been exploited for various purposes. However, the molecular basis of selenium toxicity is not completely understood. Here, we applied a capillary electrophoresis time-of-flight mass spectrometry-based metabolomics approach to analysis of yeast cells treated with selenomethionine. The data indicated that intracellular thiol compounds are significantly decreased, and diselenide and selenosulfide compounds are increased in selenomethionine-treated cells. The growth defect induced by selenomethionine was recovered by extracellular addition of cysteine and by genetic modification of yeast cells that have an additional de novo synthetic pathway for cysteine. Because cysteine is an intermediate of thiol compounds, these results suggested that the loss of a reduced form of thiol compounds due to selenomethionine causes a growth defect of yeast cells.
尽管硒是一种必需元素，但摄入过量对生物体有害。人们已经利用硒对生物体的重要性来达到各种目的。然而，硒毒性的分子基础尚未完全阐明。在这里，我们应用基于毛细管电泳飞行时间质谱的代谢组学方法分析了用硒代蛋氨酸处理的酵母细胞。数据表明，细胞内巯基化合物显著减少，而硒代蛋氨酸处理的细胞中二硒化物和硒代亚砜化合物增加。通过细胞外添加半胱氨酸和通过酵母细胞的遗传修饰（酵母细胞具有从头合成半胱氨酸的额外途径）恢复了由硒代蛋氨酸引起的生长缺陷。由于半胱氨酸是巯基化合物的中间体，这些结果表明，由于硒代蛋氨酸的存在导致还原型巯基化合物的损失会导致酵母细胞的生长缺陷。
