Yamakura Fumiyuki, Ikeda Keiichi
Department of Chemistry, Juntendo University School of Medicine, 1-1 Hiragagakuendai, Inba, Chiba 270-1606, Japan.
Nitric Oxide. 2006 Mar;14(2):152-61. doi: 10.1016/j.niox.2005.07.009. Epub 2005 Sep 2.
Formation of 3-nitrotyrosine by the reaction between reactive nitrogen species (RNS) and tyrosine residues in proteins has been analyzed extensively and it is used widely as a biomarker of pathophysiological and physiological conditions mediated by RNS. In contrast, few studies on the nitration of tryptophan have been reported. This review provides an overview of the studies on tryptophan modifications by RNS and points out the possible importance of its modification in pathophysiological and physiological conditions. Free tryptophan can be modified to several nitrated products (1-, 4-, 5-, 6-, and 7-), 1-N-nitroso product, and several oxidized products by reaction with various RNS, depending on the conditions used. Among them, 1-N-nitrosotryptophan and 6-nitrotryptophan (6-NO(2)Trp) have been found as the abundant products in the reaction with peroxynitrite, and 6-NO(2)Trp has been the most abundant product in the reaction with the peroxidase/hydrogen peroxide/nitrite systems. 6-NO(2)Trp has also been observed as the most abundant nitrated product of the reactions between peroxynitrite or myeloperoxidase/hydrogen peroxide/nitrite and tryptophan residues both in human Cu,Zn-superoxide dismutase and in bovine serum albumin, as well as the reaction of peroxynitrite with myoglobin and hemoglobin. Several oxidized products have also been identified in the modified Cu,Zn-SOD. However, no 1-N-nitrosotryptophan and 1-N-nitrotryptophan has been observed in the proteins reacted with peroxynitrite or the myeloperoxidase/H(2)O(2)/nitrite system. The modification of tryptophan residues in proteins may occur at a more limited number of sites in vivo than that of tyrosine residues, since tryptophan residues are more buried inside proteins and exist less frequently in proteins, generally. However, surface-exposed tryptophan residues tend to participate in the interaction with the other molecules, therefore the modification of those tryptophans may result in modulation of the specific interaction of proteins and enzymes with other molecules.
活性氮物质（RNS）与蛋白质中的酪氨酸残基反应生成3-硝基酪氨酸的过程已得到广泛分析，它被广泛用作RNS介导的病理生理和生理状况的生物标志物。相比之下，关于色氨酸硝化的研究报道较少。这篇综述概述了RNS对色氨酸修饰的研究，并指出其修饰在病理生理和生理状况下可能具有的重要性。游离色氨酸通过与各种RNS反应，根据所用条件可被修饰为几种硝化产物（1-、4-、5-、6-和7-）、一种1-N-亚硝基产物以及几种氧化产物。其中，1-N-亚硝基色氨酸和6-硝基色氨酸（6-NO₂Trp）已被发现是与过氧亚硝酸根反应中的主要产物，而6-NO₂Trp是与过氧化物酶/过氧化氢/亚硝酸盐体系反应中最主要的产物。在人铜锌超氧化物歧化酶、牛血清白蛋白中，以及过氧亚硝酸根与肌红蛋白和血红蛋白的反应中，6-NO₂Trp也被观察到是过氧亚硝酸根或髓过氧化物酶/过氧化氢/亚硝酸盐与色氨酸残基反应中最主要的硝化产物。在修饰的铜锌超氧化物歧化酶中也鉴定出了几种氧化产物。然而，在与过氧亚硝酸根或髓过氧化物酶/H₂O₂/亚硝酸盐体系反应的蛋白质中未观察到1-N-亚硝基色氨酸和1-N-硝基色氨酸。蛋白质中色氨酸残基的修饰在体内发生的位点数量可能比酪氨酸残基更少，因为色氨酸残基通常更多地埋藏在蛋白质内部，在蛋白质中出现的频率也较低。然而，表面暴露的色氨酸残基往往参与与其他分子的相互作用，因此这些色氨酸的修饰可能导致蛋白质和酶与其他分子的特异性相互作用受到调节。
