The chemistry of the S-nitrosoglutathione glutathione system
The chemistry of the S-nitrosoglutathione glutathione system
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DOI：
10.1073/pnas.93.25.14428
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发表时间：
1996-12-10
影响因子：
11.1
通讯作者：
Tannenbaum, SR
中科院分区：
文献类型：
--
作者：
Singh, SP;Wishnok, JS;Tannenbaum, SR
S-亚硝基硫醇由于其作为一氧化氮（NO）供体的能力以及由于其可能参与生物调节系统（例如，无转移反应。阐明S-亚硝基硫醇修饰巯基的反应途径对于理解S-亚硝基化合物在体内的作用是重要的。以谷胱甘肽（GSH）在S-亚硝基谷胱甘肽（GSNO）存在下的修饰反应为模型反应。在磷酸盐缓冲液（pH7.4）中孵育GSNO（1 mM）和各种浓度（1-10 mM）的GSH产生氧化型谷胱甘肽、亚硝酸盐、一氧化二氮和氨作为终产物。产物产率取决于GSH和氧气的浓度。通过电喷雾电离质谱鉴定了与GSH缀合物对应的瞬态信号，当用N-15标记的GSNO进行反应时，GSH缀合物增加一个质量单位。当反应体系中存在吗啉时。生成N-亚硝基吗啉。增加浓度的磷酸盐或GSH导致较低的N-亚硝基吗啉的产量。磷酸盐的抑制作用可能是由于与亚硝化剂，亚硝酸酐（N2 O3），通过NO的氧化形成的反应。这支持在GSNO与GSH反应过程中NO的释放。上述产物定量地解释了反应过程中消耗的几乎所有GSNO氮，现在可以为GSNO + GSH产生的复杂转化构建一套完整的途径。
S-Nitrosothiols have generated considerable interest due to their ability to act as nitric oxide (NO) donors and due to their possible involvement in bioregulatory systems-e.g., NO transfer reactions. Elucidation of the reaction pathways involved in the modification of the thiol group by S-nitrosothiols is important for understanding the role of S-nitroso compounds in vivo. The modification of glutathione (GSH) in the presence of S-nitrosoglutathione (GSNO) was examined as a model reaction. Incubation of GSNO (1 mM) with GSH at various concentrations (1-10 mM) in phosphate buffer (pH 7.4) yielded oxidized glutathione, nitrite, nitrous oxide, and ammonia as end products. The product yields were dependent on the concentrations of GSH and oxygen. Transient signals corresponding to GSH conjugates, which increased br one mass unit when the reaction was carried out with N-15-labeled GSNO, were identified by electrospray ionization mass spectrometry. When morpholine was present in the reaction system. N-nitrosomorpholine was formed. Increasing concentrations of either phosphate or GSH led to lower yields of N-nitrosomorpholine. The inhibitory effect of phosphate may be due to reaction with the nitrosating agent, nitrous anhydride (N2O3), formed by oxidation of NO. This supports the release of NO during the reaction of GSNO with GSH. The products noted above account quantitatively for virtually all of the GSNO nitrogen consumed during the reaction, and it is now possible to construct a complete set of pathways for the complex transformations arising from GSNO + GSH.