Studies of zinc(II) and nickel(II) complexes of GSH, GSSG and their analogs shed more light on their biological relevance.
Studies of zinc(II) and nickel(II) complexes of GSH, GSSG and their analogs shed more light on their biological relevance.
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DOI：
10.1155/s1565363304000172
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发表时间：
2004
影响因子：
3.8
通讯作者：
Bal W
中科院分区：
文献类型：
--
作者：
Krezel A;Bal W
谷胱甘肽，Y-Glu-Cys-Gly，是生物圈中最丰富的小分子之一。其主要形式是还原单体（GSH），用于解毒外源物质和重金属、减少蛋白质硫醇、维持细胞膜和灭活自由基。其氧化二聚体（GSSG）控制金属硫蛋白的金属含量。结果提供了 Zn(II)-谷胱甘肽复合物的定量和结构描述，包括新型三元 Zn(II)-GSH-His 复合物。使用 2D-NMR 获得了该配合物的溶液结构。研究的复合物可能有助于锌和谷胱甘肽的生理学。在 Ni(II) 络合物的情况下，发现了配位模式对反应物比率的有趣依赖性。当GSH过量时，形成Ni(GSH) 2 络合物，其中Ni(II)通过S和N和/或O供体原子键合。该配合物可能以高自旋或低自旋物质的形式存在。研究的另一个目标是描述 Ni(II) 离子对 GSH 氧化的催化特性，这似乎是镍致癌的重要一步。氧化速率的 pH 依赖性可以确定 Ni(GSH)2 络合物是毒理学相关物种中最活跃的。还详细研究了无金属 GSH 及其类似物的质子化和氧化。 GSH 的单质子化形式 HL2- 是最容易氧化的形式，因为 S- 和 NH3+ 基团之间存在盐桥，从而激活硫醇。
Glutathione, Υ-Glu-Cys-Gly, is one of the most abundant small molecules in biosphere. Its main form is the reduced monomer (GSH), serving to detoxicate xenobiotics and heavy metals, reduce protein thiols, maintain cellular membranes and deactivate free radicals. Its oxidized dimer (GSSG) controls metal content of metallothionein. The results presented provided a quantitative and structural description of Zn(II)- glutathione complexes, including a novel ternary Zn(II)-GSH-His complex. A solution structure for this complex was obtained using 2D-NMR. The Complexes studied may contribute to both zinc and glutathione physiology. In the case of Ni(ll) complexes an interesting dependence of coordination modes on the ratios of reactants was found. At high GSH excess a Ni(GSH)2 complex is formed, with Ni(ll) bonded through S and N and/or O donor atoms. This complex may exist as a high- or low-spin species. Another goal of the studies presented was to describe the catalytic properties of Ni(II) ions towards GSH oxidation, which appeared to be an important step in nickel carcinogenesis. The pH dependence of oxidation rates allowed to determine the Ni(GSH)2 complex as the most active among the toxicologically relevant species. Protonation and oxidation of metal-free GSH and its analogues were also studied in detail. The monoprotonated form HL2- of GSH is the one most susceptible to oxidation, due to a salt bridge between S- and NH3+ groups, which activates the thiol.