Characterization of the oxidation products of the reaction between reduced glutathione and hypochlorous acid
Characterization of the oxidation products of the reaction between reduced glutathione and hypochlorous acid
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DOI：
10.1042/bj3260087
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发表时间：
1997-08-15
影响因子：
4.1
通讯作者：
Brennan, SO
中科院分区：
文献类型：
--
作者：
Winterbourn, CC;Brennan, SO
还原性谷胱甘肽（GSH）是骨髓过氧化物酶衍生的次氯酸的首选生物底物之一，是中性粒细胞氧化剂的可能靶点。我们用高效液相色谱法表明，次氯酸氧化谷胱甘肽，除了谷胱甘肽二硫化（GSSG）外，还产生两种主要的稳定产物。最常见的产物缺乏游离胺和巯基，电喷雾质谱显示其分子质量为337 Da。这对应于谷胱甘肽获得了两个氧原子而失去了两个氢原子，并且与产物是内部磺胺相一致。另一种新产物分子量为644 Da，含有胺基，但不含游离硫醇。这些性质与它是谷胱甘肽硫代磺酸盐一致。虽然细胞中的GSSG是酶循环的，但这些高氧化产物的形成可能是不可逆的。因此，次氯酸可以通过消耗谷胱甘肽来损害细胞。假定的磺胺可能是唯一的被次氯酸氧化的，因此提供了一个有用的中性粒细胞氧化活性标记。
Reduced glutathione (GSH) is one of the most preferred biological substrates of myeloperoxidase-derived hypochlorous acid and is a likely target for neutrophil oxidants. We have used HPLC to show that the oxidation of GSH by hypochlorous acid gives two major, stable products in addition to glutathione disulphide (GSSG). The most prevalent product lacks free amine and thiol groups, and was shown by electrospray MS to have a molecular mass of 337 Da. This corresponds to GSH with a gain of two oxygen atoms and a loss of two hydrogen atoms, and is consistent with the product being an internal sulphonamide. The other novel product has a molecular mass of 644 Da, and has amine groups but no free thiols. These properties are consistent with it being glutathione thiolsulphonate. Whereas GSSG in the cell is recycled enzymically, formation of these higher oxidation products is likely to be irreversible. Hypochlorous acid, therefore, could compromise the cell by depleting GSH. The putative sulphonamide may be unique for oxidation by hypochlorous acid and thus provide a useful marker of neutrophil oxidant activity.