A novel reaction mechanism for the formation of S-nitrosothiol in vivo
A novel reaction mechanism for the formation of S-nitrosothiol in vivo
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DOI：
10.1074/jbc.272.5.2841
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发表时间：
1997-01-31
影响因子：
4.8
通讯作者：
Ischiropoulos, H
中科院分区：
文献类型：
--
作者：
Gow, AJ;Buerk, DG;Ischiropoulos, H
本研究的目的是探讨在生理条件下S-亚硝基硫醇的形成机制。一氧化氮（（NO）-N-。）直接与还原硫醇反应生成自由基中间体R-S-N-。哦该中间体还原电子受体以产生S-亚硝基硫醇。在有氧条件下，O-2作为电子受体，被还原产生超氧化物（O-2（自由基阴离子））。下面的实验证据提供了支持这一机制。半胱氨酸加速（NO）-N-的消耗。在生理条件下增加了2.5倍在（NO）-N-存在下O-2的消耗。半胱氨酸增加了2.4倍。（NO）-N-的反应级数。和半胱氨酸分别为二级和一级。（NO）-N-的二级反应。可能是由（NO）-N-之间的相互作用引起的。和O-2（自由基阴离子）形成过氧亚硝酸根。在Cu，Zn-超氧化物歧化酶存在下，（NO）-N-。与半胱氨酸反应生成过氧化氢，表明反应生成O-2（自由基阴离子）。最后，S-亚硝基硫醇的形成被证明在厌氧环境中，并预测的机制，是依赖于电子受体的存在。这些结果表明，在生理条件下（NO）-N-。在电子受体存在下，直接与硫醇反应形成S-亚硝基硫醇。
The objective of this study was to investigate the mechanism of S-nitrosothiol formation under physiological conditions. A mechanism is proposed by which nitric oxide ((NO)-N-.) reacts directly with reduced thiol to produce a radical intermediate, R-S-N-.-O-H. This intermediate reduces an electron acceptor to produce S-nitrosothiol. Under aerobic conditions O-2 acts as the electron acceptor and is reduced to produce superoxide (O-2(radical anion)). The following experimental evidence is provided in support of this mechanism. Cysteine accelerates the consumption of (NO)-N-. by 2.5-fold under physiological conditions. The consumption of O-2 in the presence of (NO)-N-. and cysteine is increased by 2.4-fold. The reaction orders of (NO)-N-. and cysteine are second and first order, respectively. The second order of reaction for (NO)-N-. may result from interaction between (NO)-N-. and O-2(radical anion) to form peroxynitrite. In the presence of Cu,Zn-superoxide dismutase, the reaction of (NO)-N-. with cysteine generates hydrogen peroxide, indicating that the reaction generates O-2(radical anion). Finally, the formation of S-nitrosothiol is demonstrated in an anaerobic environment and, as predicted by the mechanism, is dependent on the presence of an electron acceptor. These results demonstrate that under physiological conditions (NO)-N-. reacts directly with thiols to form S-nitrosothiol in the presence of an electron acceptor.