Fundamentals on the biochemistry of peroxynitrite and protein tyrosine nitration.
Fundamentals on the biochemistry of peroxynitrite and protein tyrosine nitration.
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DOI：
10.1016/j.redox.2017.09.009
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发表时间：
2018-04
期刊：
影响因子：
11.4
通讯作者：
Radi R
中科院分区：
文献类型：
--
作者：
Bartesaghi S;Radi R
在这篇综述中，我们提供了一个分析的生物化学过氧亚硝酸盐和酪氨酸硝化。过氧亚硝酸盐是超氧化物（O2·-）和一氧化氮（·NO）之间扩散控制反应的产物。该过程与O2·-的酶促歧化和·NO在细胞和组织中的扩散及其与分子靶点（例如鸟苷酸环化酶）的反应竞争。了解O2·- / ·NO相互作用的动力学和区室化对于合理化·NO从生理介质到细胞毒性中间体的转变至关重要。一旦形成，过氧亚硝酸盐（ONOO-和ONOOH; pKa = 6，8）的行为作为一个强大的一个和两个电子的氧化剂对一系列的生物分子，包括过渡金属中心和硫醇。此外，过氧亚硝酸根阴离子可以通过与CO2的快速反应或通过质子催化的均裂而次级演化为次级自由基。因此，过氧亚硝酸盐可以参与直接（双分子）和间接（通过二级自由基中间体）氧化反应;通过这些过程，过氧亚硝酸盐可以作为细胞毒性效应分子参与对抗入侵病原体和/或作为内源性致病介质。过氧亚硝酸盐在体内外均可引起蛋白质酪氨酸硝化。事实上，酪氨酸硝化是细胞和组织中·NO衍生的氧化剂反应的标志，并作为氧化损伤的生物标志物。蛋白质酪氨酸硝化可以介导蛋白质结构和功能的变化，从而影响细胞内稳态。生物体系中的酪氨酸硝化是一个自由基过程，可以通过过氧亚硝酸根衍生的自由基或其他相关的·NO依赖性氧化过程来促进。最近，负责酪氨酸硝化的疏水生物结构，如膜和脂蛋白的机制已被评估，并涉及与脂质过氧化的平行发生和连接。实验策略，以揭示在给定的病理生理相关的条件下酪氨酸硝化过程中的近端氧化机制，包括映射和识别特定蛋白质中的酪氨酸硝化位点。过氧亚硝酸盐是由超氧化物和一氧化氮自由基形成的反应性过氧化物。过氧亚硝酸盐是一种强的单电子和双电子氧化剂。蛋白质酪氨酸硝化需要自由基反应。3-硝基酪氨酸是硝基氧化应激的生物标志物。关键蛋白酪氨酸的硝化导致蛋白质功能的变化。
In this review we provide an analysis of the biochemistry of peroxynitrite and tyrosine nitration. Peroxynitrite is the product of the diffusion-controlled reaction between superoxide (O2•-) and nitric oxide (•NO). This process is in competition with the enzymatic dismutation of O2•- and the diffusion of •NO across cells and tissues and its reaction with molecular targets (e.g. guanylate cyclase). Understanding the kinetics and compartmentalization of the O2•- / •NO interplay is critical to rationalize the shift of •NO from a physiological mediator to a cytotoxic intermediate. Once formed, peroxynitrite (ONOO- and ONOOH; pKa = 6,8) behaves as a strong one and two-electron oxidant towards a series of biomolecules including transition metal centers and thiols. In addition, peroxynitrite anion can secondarily evolve to secondary radicals either via its fast reaction with CO2 or through proton-catalyzed homolysis. Thus, peroxynitrite can participate in direct (bimolecular) and indirect (through secondary radical intermediates) oxidation reactions; through these processes peroxynitrite can participate as cytotoxic effector molecule against invading pathogens and/or as an endogenous pathogenic mediator. Peroxynitrite can cause protein tyrosine nitration in vitro and in vivo. Indeed, tyrosine nitration is a hallmark of the reactions of •NO-derived oxidants in cells and tissues and serves as a biomarker of oxidative damage. Protein tyrosine nitration can mediate changes in protein structure and function that affect cell homeostasis. Tyrosine nitration in biological systems is a free radical process that can be promoted either by peroxynitrite-derived radicals or by other related •NO-dependent oxidative processes. Recently, mechanisms responsible of tyrosine nitration in hydrophobic biostructures such as membranes and lipoproteins have been assessed and involve the parallel occurrence and connection with lipid peroxidation. Experimental strategies to reveal the proximal oxidizing mechanism during tyrosine nitration in given pathophysiologically-relevant conditions include mapping and identification of the tyrosine nitration sites in specific proteins. Peroxynitrite is a reactive peroxide formed from superoxide and nitric oxide radicals. Peroxynitrite is a strong one- and two-electron oxidant. Protein tyrosine nitration requires free radical reactions. 3-Nitrotyrosine is a biomarker of nitroxidative stress. Nitration of key protein tyrosines leads to changes in protein function.
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DOI：
10.1007/978-3-319-45865-6_5
发表时间：
2016-01-01
期刊：
BIOCHEMISTRY OF OXIDATIVE STRESS: PHYSIOPATHOLOGY AND CLINICAL ASPECTS
影响因子：
--
作者：
Aicardo, Adrian;Martinez, Debora M.;Radi, Rafael
通讯作者：
Radi, Rafael
影响因子：
3.3
作者：
Douki, T;Cadet, J
通讯作者：
Cadet, J
影响因子：
3.8
作者：
Campolo, Nicolas;Bartesaghi, Silvina;Radi, Rafael
通讯作者：
Radi, Rafael
影响因子：
3
作者：
Carballal, Sebastian;Bartesaghi, Silvina;Radi, Rafael
通讯作者：
Radi, Rafael
影响因子：
7.4
作者：
Bayden, Alexander S.;Yakovlev, Vasily A.;Graves, Paul R.;Mikkelsen, Ross B.;Kellogg, Glen E.
通讯作者：
Kellogg, Glen E.