过氧亚硝酸盐的生物化学和蛋白质酪氨酸的硝化,Chemical Reviews

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过氧亚硝酸盐的生物化学和蛋白质酪氨酸的硝化
Chemical Reviews ( IF 51.4 ) Pub Date : 2018-02-05 00:00:00 , DOI: 10.1021/acs.chemrev.7b00568
Gerardo Ferrer-Sueta ₁ , Nicolás Campolo ₁ , Madia Trujillo ₁ , Silvina Bartesaghi ₁ , Sebastián Carballal ₁ , Natalia Romero ₁ , Beatriz Alvarez ₁ , Rafael Radi ₁

Affiliation

过氧亚硝酸盐是由自由基超氧化物（O ₂^•–）和一氧化氮（^• NO）的扩散控制反应形成的一种短时反应性生物氧化剂。在这篇综述中，我们首先分析体内过氧亚硝酸盐形成的生物化学证据以及导致其的反应。然后，我们描述了过氧亚硝酸盐与生物靶标发生的主要反应，并提供了动力学和机理上的细节。在这些反应中，过氧亚硝酸盐具有以下作用：（1）过氧化物，（2）Lewis碱和（3）自由基产生剂。CO _2的生理水平可以改变过亚硝酸盐反应的结果。审查的第二部分评估了蛋白质3-硝基酪氨酸（NO ₂的Tyr）通过过氧亚硝酸盐依赖性和非依赖性机制，随着动作的标志之一^• NO衍生氧化剂在生物系统中。此外，酪氨酸硝化影响蛋白质的结构和功能，酪氨酸激酶信号转导级联和蛋白质更新。总的来说，本综述旨在就生物相关条件下过氧亚硝酸盐的形成和反应，以及这种隐形氧化剂及其主要足迹之一的蛋白质NO ₂ Tyr在破坏细胞稳态中的作用提供一个综合的生物化学观点。

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Biochemistry of Peroxynitrite and Protein Tyrosine Nitration

Peroxynitrite is a short-lived and reactive biological oxidant formed from the diffusion-controlled reaction of the free radicals superoxide (O₂^•–) and nitric oxide (^•NO). In this review, we first analyze the biochemical evidence for the formation of peroxynitrite in vivo and the reactions that lead to it. Then, we describe the principal reactions that peroxynitrite undergoes with biological targets and provide kinetic and mechanistic details. In these reactions, peroxynitrite has roles as (1) peroxide, (2) Lewis base, and (3) free radical generator. Physiological levels of CO₂ can change the outcome of peroxynitrite reactions. The second part of the review assesses the formation of protein 3-nitrotyrosine (NO₂Tyr) by peroxynitrite-dependent and -independent mechanisms, as one of the hallmarks of the actions of ^•NO-derived oxidants in biological systems. Moreover, tyrosine nitration impacts protein structure and function, tyrosine kinase signal transduction cascades and protein turnover. Overall, the review is aimed to provide an integrated biochemical view on the formation and reactions of peroxynitrite under biologically relevant conditions and the impact of this stealthy oxidant and one of its major footprints, protein NO₂Tyr, in the disruption of cellular homeostasis.

更新日期：2018-02-05

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