Dickinson Dale A, Forman Henry Jay
Department of Environmental Health Sciences, Center for Free Radical Biology, School of Public Health, University of Alabama at Birmingham, 1530 3rd Avenue S, RPHB-317, Birmingham, AL 35294-0022, USA.
Biochem Pharmacol. 2002 Sep;64(5-6):1019-26. doi: 10.1016/s0006-2952(02)01172-3.
Low molecular weight thiol-containing compounds have an essential role in many biochemical and pharmacological reactions due to the ease with each they are oxidized, and the rapidity with which they can be regenerated. Thioredoxin and glutathione (GSH) are two of the major small molecular weight thiol-containing compounds synthesized de novo in mammalian cells that participate in those functions. Understanding the mechanisms of thiol metabolism has special relevance to understanding the cell's defense against toxicant exposure and as the focal point in redox signaling. This commentary will, however, focus on GSH consumption and synthesis, and the role of thiols in signaling. The chemical reactions of GSH, including conjugation reactions mediated by glutathione S-transferases (GST) and oxidation reactions mediated by glutathione peroxidases will be described. The regulation of GSH synthesis will be illustrated from a compilation of studies designed to understand the various levels at which enzymatic GSH biosynthesis is controlled, and the signaling pathways that mediate them. The response of the cell to 4-hydroxynonenal (4HNE), a reactive aldehyde produced physiologically in response to inflammation and various air pollutants, will be explored in detail. Finally, the direct role of thiols as signaling molecules will be addressed, with particular attention given to "redox state." It is our aim that this commentary will lead the reader to appreciate that studies investigating the signaling for and regulation of thiol metabolism must never be generalized, and that perturbations in any of step of thiol metabolism may have etiological roles in genetically, virally, and environmentally borne pathologies.
低分子量含硫醇化合物在许多生物化学和药理反应中起着至关重要的作用，这是因为它们易于被氧化，且能够快速再生。硫氧还蛋白和谷胱甘肽（GSH）是哺乳动物细胞中从头合成的两种主要的低分子量含硫醇化合物，参与这些功能。了解硫醇代谢机制对于理解细胞对毒物暴露的防御以及作为氧化还原信号传导的焦点具有特殊意义。然而，本评论将重点关注谷胱甘肽的消耗和合成，以及硫醇在信号传导中的作用。将描述谷胱甘肽的化学反应，包括由谷胱甘肽S-转移酶（GST）介导的结合反应和由谷胱甘肽过氧化物酶介导的氧化反应。将通过一系列旨在了解酶促谷胱甘肽生物合成在各个水平上的控制以及介导这些控制的信号通路的研究汇编来说明谷胱甘肽合成的调节。将详细探讨细胞对4-羟基壬烯醛（4HNE）的反应，4HNE是一种在生理上响应炎症和各种空气污染物而产生的反应性醛。最后，将探讨硫醇作为信号分子的直接作用，特别关注“氧化还原状态”。我们的目的是，本评论将引导读者认识到，研究硫醇代谢信号传导和调节的研究绝不能一概而论，硫醇代谢任何一步的扰动都可能在遗传、病毒和环境引起的病理学中具有病因学作用。
