Peroxynitrite reactivity with amino acids and proteins

Peroxynitrite reactivity with amino acids and proteins
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DOI:
10.1007/s00726-003-0018-8
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发表时间:
2003-12-01
期刊:
影响因子:
3.5
通讯作者:
Radi, R
Radi, R
中科院分区:
生物学3区
文献类型:
--
作者:
Alvarez, B;Radi, R

文献摘要

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过氧亚硝酸盐,一氧化氮((NO)-N-.)和超氧阴离子O-2(.-)自由基是一种氧化剂和硝化剂,能够穿过生物膜。过氧亚硝酸盐与蛋白质的反应通过三种可能的途径发生。首先,过氧亚硝酸盐直接与半胱氨酸、甲硫氨酸和色氨酸残基反应。第二,过氧亚硝酸盐与过渡金属中心和含硒氨基酸快速反应。第三,由过氧亚硝酸盐均裂产生的二级自由基,如羟基和二氧化氮,以及在二氧化碳存在下形成的碳酸根,也与蛋白质部分反应。酪氨酸残基的硝化被认为是一氧化氮对氧化损伤贡献的标志。过氧亚硝酸盐依赖的酪氨酸硝化可能通过过氧亚硝酸盐与二氧化碳或金属中心的初始反应而发生,导致二次硝化物种。过氧亚硝酸盐的优先蛋白质的目标和蛋白质的过氧亚硝酸盐解毒途径中的作用进行了讨论。
Peroxynitrite, the product of the fast reaction between nitric oxide ((NO)-N-.) and superoxide O-2(.-) radicals, is an oxidizing and nitrating agent which is able to traverse biological membranes. The reaction of peroxynitrite with proteins occurs through three possible pathways. First, peroxynitrite reacts directly with cysteine, methionine and tryptophan residues. Second, peroxynitrite reacts fast with transition metal centers and selenium-containing amino acids. Third, secondary free radicals arising from peroxynitrite homolysis such as hydroxyl and nitrogen dioxide, and the carbonate radical formed in the presence of carbon dioxide, react with protein moieties too. Nitration of tyrosine residues is being recognized as a marker of the contribution of nitric oxide to oxidative damage. Peroxynitrite-dependent tyrosine nitration is likely to occur through the initial reaction of peroxynitrite with carbon dioxide or metal centers leading to secondary nitrating species. The preferential protein targets of peroxynitrite and the role of proteins in peroxynitrite detoxifying pathways are discussed.