Cellular glutathione and thiols metabolism
Cellular glutathione and thiols metabolism
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DOI：
10.1016/s0006-2952(02)01172-3
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发表时间：
2002-09-01
影响因子：
5.8
通讯作者：
Forman, HJ
中科院分区：
文献类型：
--
作者：
Dickinson, DA;Forman, HJ
低分子量含硫醇化合物在许多生物化学和药理学反应中具有重要作用，这是由于它们各自容易被氧化，并且它们可以快速再生。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小分子量含巯基化合物，参与这些功能。了解硫醇代谢的机制对于了解细胞对毒物暴露的防御具有特殊意义，并且是氧化还原信号传导的焦点。然而，这篇评论将集中在GSH的消耗和合成，以及硫醇在信号传导中的作用。谷胱甘肽的化学反应，包括由谷胱甘肽S-转移酶（GST）介导的共轭反应和谷胱甘肽过氧化物酶介导的氧化反应将被描述。GSH合成的调节将说明从汇编的研究，旨在了解酶促GSH生物合成的控制，以及介导它们的信号通路的各个水平。将详细探讨细胞对4-羟基壬烯醛（4HNE）的反应，4-羟基壬烯醛是一种反应性醛，在炎症和各种空气污染物的生理反应中产生。最后，硫醇作为信号分子的直接作用将得到解决，特别注意“氧化还原状态”。“我们的目标是，这篇评论将引导读者认识到，研究硫醇代谢的信号传导和调节的研究决不能被泛化，硫醇代谢任何步骤的扰动都可能在遗传、病毒和环境传播的病理中起病因学作用。(C)2002年爱思唯尔科技有限公司All rights reserved.
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. (C) 2002 Elsevier Science Inc. All rights reserved.