Thiolation and nitrosation of cysteines in biological fluids and cells
Thiolation and nitrosation of cysteines in biological fluids and cells
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DOI：
10.1007/s00726-003-0020-1
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发表时间：
2003-12-01
期刊：
影响因子：
3.5
通讯作者：
Di Giuseppe, D
中科院分区：
文献类型：
--
作者：
Di Simplicio, P;Franconi, F;Di Giuseppe, D
硫醇 (RSH) 是有效的亲核试剂，其速率取决于巯基的 pKa。与具有其他亲核基团（-OH 或 -NH2）的化合物不同，RSH 参与共轭、氧化还原和交换反应等反应。尽管蛋白质 SH 基团 (PSH) 的反应类似于非蛋白质硫醇 (NPSH)，但由于空间位阻、电荷分布以及 PSH 对溶剂的可及性（蛋白质构象）等原因，蛋白质的生物化学要复杂得多。 PSH 的反应速率和终产物类型因蛋白质而异。生物学问题更加复杂，因为在所有区室和组织中，硫醇之间（即 GSH 和 PSH 之间）可能存在特定的竞争，并受到抗氧化酶特性的调节。此外，PSH在生物学上分为必需的和非必需的，并且它们各自在各种生物系统中的影响尚不清楚。由此可见，在引发迅速硫醇反应（氧化应激）的现象中，抗氧化剂 PSH 反应和反应机制因情况而异。例如，尽管白蛋白的 pKa 相对较低，可以保证良好的抗氧化能力，但与 NPSH 相比，白蛋白的 PSH 与缀合剂形成加合物的倾向要小得多；此外，蛋白质的结构特征可防止白蛋白在暴露于氧化剂时形成蛋白质二硫化物（而蛋白质-硫醇混合二硫化物的形成相对丰富）。另一方面，反应活性较高的蛋白质，如大鼠血红蛋白，其抗氧化能力比GSH大得多，但人血红蛋白虽然具有与GSH相似的pKa，但由于结构原因，其抗氧化能力低于GSH。当必需的PSH参与S-硫醇化和S-亚硝化反应时，观察到类似的生物活性变化。 S-硫醇化蛋白是活性氧 (ROS) 引起的氧化应激中反复出现的现象。该事件可能由与 PSH 交换的二硫化物介导，或由与硫醇反应形成蛋白质混合二硫化物的蛋白质中间体次磺酸介导。在活性氮 (RNS) 引起的亚硝化应激过程中，根据系统的氧浓度，硫醇的亚硝化反应也可能伴随蛋白质 S-硫醇化。在这篇综述中，我们讨论了许多细胞过程和酶的生化修饰，这些修饰表明在 ROS 和 RNS 之间存在适当相互作用的情况下，同一蛋白质中可能同时发生 S-硫醇化和 S-亚硝化。
Thiols (RSH) are potent nucleophilic agents, the rates of which depend on the pKa of the sulfhydryl. Unlike compounds having other nucleophile moieties (-OH or -NH2), RSH are involved in reactions, such as conjugations, redox and exchange reactions. Although protein SH groups (PSH) react like non-protein thiols (NPSH), the biochemistry of proteins is much more complex for reasons such as steric hindrance, charge distribution and accessibility of PSH to the solvent (protein conformation). The reaction rates and types of end-products of PSH vary a lot from protein to protein. The biological problem is even more complex because in all compartments and tissues, there may be specific competition between thiols (namely between GSH and PSH), regulated by the properties of antioxidant enzymes. Moreover, PSH are divided biologically into essential and non-essential and their respective influence in the various biological systems is unknown. It follows that during phenomena eliciting a prompt thiol response (oxidative stress), the antioxidant PSH response and reaction mechanisms vary considerably from case to case. For example, in spite of a relatively low pKa that should guarantee good antioxidant capacity, PSH of albumin has much less propensity to form adducts with conjugating agents than NPSH; moreover, the structural characteristics of the protein prevent albumin from forming protein disulfides when exposed to oxidants (whereas protein-thiol mixed disulfides are formed in relative abundance). On the other hand, proteins with a relatively high reactivity, such rat hemoglobin, have much greater antioxidant capacity than GSH, but although human hemoglobin has a pKa similar to GSH, for structural reasons it has less antioxidant capacity than GSH.When essential PSH are involved in S-thiolation and S-nitrosation reactions, a similar change in biological activity is observed. S-thiolated proteins are a recurrent phenomenon in oxidative stress elicited by reactive oxygen species (ROS). This event may be mediated by disulfides, that exchange with PSH, or by the protein intermediate sulfenic acid that reacts with thiols to form protein-mixed disulfides. During nitrosative stress elicited by reactive nitrogen species (RNS), depending on the oxygen concentration of the system, nitrosation reactions of thiols may also be accompanied by protein S-thiolation. In this review we discuss a number of cell processes and biochemical modifications of enzymes that indicate that S-thiolation and S-nitrosation may occur simultaneously in the same protein in the presence of appropriate interactions between ROS and RNS.