Mechanism of nitric oxide release from S-nitrosothiols
Mechanism of nitric oxide release from S-nitrosothiols
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DOI：
10.1074/jbc.271.31.18596
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发表时间：
1996-08-02
影响因子：
4.8
通讯作者：
Kalyanaraman, B
中科院分区：
文献类型：
--
作者：
Singh, RJ;Hogg, N;Kalyanaraman, B
S-亚硝基硫醇具有多种生物活性，被认为是信号转导的中间体。S-亚硝基硫醇分解的机理和产物对理解一氧化氮（（NO）-N-.）生物化学S-亚硝基硫醇在37 ℃和pH 7.4下在过渡金属离子螯合剂存在下是稳定的化合物。痕量过渡金属离子（存在于所有缓冲液中）的存在刺激S-亚硝基硫醇催化分解为（NO）-N-。和二硫化物。在这个过程中，巯基不是作为中间体形成的; S-亚硝基硫醇的光解导致（NO）-N-的形成。和二硫化物通过中间的硫基自由基。还原的金属离子（例如Cu+）比氧化的金属离子（例如Cu 2+）更快地分解S-亚硝基硫醇，这表明还原剂如谷胱甘肽和抗坏血酸盐可以通过污染过渡金属离子的化学还原来刺激S-亚硝基硫醇的分解。如果产物S-亚硝基硫醇比母体S-亚硝基硫醇更易受过渡金属离子催化分解的影响，则反亚硝化也可刺激S-亚硝基硫醇分解。还原型谷胱甘肽与S-亚硝基-N-乙酰基-DL-青霉胺或S-亚硝基-L-半胱氨酸的转亚硝化反应的平衡常数表明S-亚硝基谷胱甘肽的形成是有利的。S-亚硝基硫醇分解的生物相关性进行了讨论。
S-Nitrosothiols have many biological activities and have been suggested to be intermediates in signal transduction. The mechanism and products of S-nitrosothiol decomposition are of great significance to the understanding of nitric oxide ((NO)-N-.) biochemistry. S-Nitrosothiols are stable compounds at 37 degrees C and pH 7.4 in the presence of transition metal ion chelators. The presence of trace transition metal ions (present in all buffers) stimulates the catalytic breakdown of S-nitrosothiols to (NO)-N-. and disulfide. Thiyl radicals are not formed as intermediates in this process; Photolysis of S-nitrosothiols results in the formation of (NO)-N-. and disulfide via the intermediacy of thiyl radicals. Reduced metal ion (e.g, Cu+) decomposes S-nitrosothiols more rapidly than oxidized metal ion (e.g. Cu2+) indicating that reducing agents such as glutathione and ascorbate can stimulate decomposition of S-nitrosothiol by chemical reduction of contaminating transition metal ions. Transnitrosation can also stimulate S-nitrosothiol decomposition if the product S-nitrosothiol is more susceptible to transition metal ion-catalyzed decomposition than the parent S-nitrosothiol. Equilibrium constants for the transnitrosation reactions of reduced glutathione, either with S-nitroso-N-acetyl-DL-penicillamine or with S-nitroso-L-cysteine indicate that S-nitrosoglutathione formation is favored. The biological relevance of S-nitrosothiol decomposition is discussed.