{"title":"[The Role of Supersulfide in Methylmercury Detoxification].","authors":"Takashi Toyama, Runa Kudo, Yoshiro Saito","doi":"10.1248/yakushi.23-00162-1","DOIUrl":null,"url":null,"abstract":"<p><p>Methylmercury is a ubiquitous neurotoxic substance present in the environment, and health concerns, especially through the consumption of seafood, remain. Glutathione (GSH)-mediated detoxification and the excretion of methylmercury are known metabolic detoxification pathways. We have also discovered a mechanism by which endogenous super-sulfides convert methylmercury to nontoxic metabolites such as bis-methylmercury sulfide. However, these metabolites are present in very small quantities, and the significance of the detoxification of methylmercury by super-sulfides is not well understood. Methylmercury binds to thiol groups in vivo but can also react with highly reactive selenols (selenocysteine residues). Such covalent bonds (S-mercuration and Se-mercuration) are broken by nucleophilic substitution reactions with other thiol and selenols, however, the contribution of super-sulfides to this substitution reaction is not well understood. Interestingly, a recent study suggested that selenoprotein P, the major selenium transport protein in plasma, binds to methylmercury, however, Se-mercuration was not determined. In this review, we introduce these series of reactions and discuss their involvement with super-sulfides in methylmercury toxicity.</p>","PeriodicalId":23810,"journal":{"name":"Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan","volume":null,"pages":null},"PeriodicalIF":0.3000,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1248/yakushi.23-00162-1","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
引用次数: 0
Abstract
Methylmercury is a ubiquitous neurotoxic substance present in the environment, and health concerns, especially through the consumption of seafood, remain. Glutathione (GSH)-mediated detoxification and the excretion of methylmercury are known metabolic detoxification pathways. We have also discovered a mechanism by which endogenous super-sulfides convert methylmercury to nontoxic metabolites such as bis-methylmercury sulfide. However, these metabolites are present in very small quantities, and the significance of the detoxification of methylmercury by super-sulfides is not well understood. Methylmercury binds to thiol groups in vivo but can also react with highly reactive selenols (selenocysteine residues). Such covalent bonds (S-mercuration and Se-mercuration) are broken by nucleophilic substitution reactions with other thiol and selenols, however, the contribution of super-sulfides to this substitution reaction is not well understood. Interestingly, a recent study suggested that selenoprotein P, the major selenium transport protein in plasma, binds to methylmercury, however, Se-mercuration was not determined. In this review, we introduce these series of reactions and discuss their involvement with super-sulfides in methylmercury toxicity.
甲基汞是一种普遍存在于环境中的神经毒性物质,其健康问题,尤其是通过食用海产品引起的健康问题仍然存在。谷胱甘肽(GSH)介导的解毒和甲基汞的排泄是已知的代谢解毒途径。我们还发现了内源性超硫化物将甲基汞转化为双甲基硫化汞等无毒代谢物的机制。然而,这些代谢物的含量非常小,而且人们对超硫化物对甲基汞解毒的意义还不甚了解。甲基汞在体内会与硫醇基团结合,但也会与高活性硒醇(硒代半胱氨酸残基)发生反应。这种共价键(S-巯基化和 Se-巯基化)会通过与其他硫醇和硒醇的亲核置换反应而断裂,然而,人们对超硫化物在这种置换反应中的作用还不甚了解。有趣的是,最近的一项研究表明,血浆中主要的硒转运蛋白硒蛋白 P 可与甲基汞结合,但硒化作用并未确定。在本综述中,我们将介绍这一系列反应,并讨论它们与超硫化物在甲基汞毒性中的关系。