Transnitrosation of thiols from aliphatic N-nitrosamines:: S-nitrosation and indirect generation of nitric oxide
Transnitrosation of thiols from aliphatic N-nitrosamines:: S-nitrosation and indirect generation of nitric oxide
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DOI：
10.1021/ja0658259
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发表时间：
2007-01-31
影响因子：
15
通讯作者：
Ohwada, Tomohiko
中科院分区：
文献类型：
--
作者：
Yanagimoto, Takahiro;Toyota, Takeshi;Ohwada, Tomohiko
S-亚硝基硫醇和血红素亚硝酰基物质是一氧化氮（NO）衍生的代谢物，其提供NO的内源性储库，并且还在蛋白质S-亚硝化中发挥作用，S-亚硝化即蛋白质中硫醇（或硫醇盐）的转亚硝化，从而调节蛋白质功能和信号转导途径。有趣的是，内源性N-亚硝胺的丰度与S-亚硝基硫醇相似，尽管它们被认为与S-亚硝基硫醇具有相似的生理作用，但它们的转亚硝化反应性及其对生物事件的贡献却知之甚少。本文报道了7-氮杂双环[2.2.1]庚烷的脂肪族N-亚硝基衍生物，它们本身不作为NO供体，但可以使硫醇发生亚硝化反应。根据计算的这些N-亚硝胺的反亚硝化活化能和主动脉平滑肌舒张活性，我们提出了一种可能的情况下，S-反亚硝化从脂肪族N-亚硝胺，导致NO的间接产生。
S-Nitrosothiols and heme nitrosyl species are nitric oxide (NO)-derived metabolites that provide an endogenous reservoir of NO and also play roles in protein S-nitrosation, that is, transnitrosation of thiols (or thiolates) in proteins, thereby regulating protein functions and signal transduction pathways. Intriguingly, endogenous N-nitrosamines are present in similar abundance to S-nitrosothiols, and though they are thought to play similar physiological roles to S-nitrosothiols, their transnitrosation reactivities and their contribution to biological events are little understood. Herein we report aliphatic N-nitroso derivatives of 7-azabicyclo[2.2.1]heptanes, which do not act as NO donors themselves, but can transnitrosate thiols. On the basis of the calculated activation energies of transnitrosation and the aorta smooth-muscle relaxation activities of these N-nitrosamines, we present a possible scenario of Stransnitrosation from aliphatic N-nitrosamines, leading to indirect generation of NO.