PEROXYNITRITE MODIFICATION OF ENZYMES

内源性过氧亚硝酸盐对脂质、蛋白质和核酸的细胞损伤与许多神经系统疾病有关。本实验室早期的研究结果表明，过氧亚硝酸盐损伤蛋白质的能力强烈依赖于氢离子浓度和二氧化碳的生理水平，并且它可能对蛋白质羰基衍生物的形成或蛋氨酸残基的氧化没有显著贡献，这两者都是广泛使用的氧化蛋白质损伤标志物。在确定蛋白质依赖过氧亚硝酸盐修饰的主要靶点的持续研究中，测定了过氧亚硝酸盐对牛血清白蛋白（BSA）和谷氨酰胺合成酶（GS）中硝酸盐酪氨酸残基的能力。虽然这两种蛋白质每个亚基含有几乎相同数量的酪氨酸残基，但它们表现出明显不同的过氧亚硝酸盐依赖硝化的ph依赖谱。因此，很明显，蛋白质酪氨酸残基的硝化作用强烈依赖于酪氨酸残基的分子分布和蛋白质构象。-过氧亚硝酸盐，蛋白质羰基，过氧亚硝酸盐-二氧化碳加合物

Cellular damage to lipids, proteins, and nucleic acids by endogenously generated peroxynitrite is associated with a number of neurological diseases. Results of earlier studies in this laboratory demonstrated that the ability of peroxynitrite to damage proteins is strongly dependent upon the hydrogen ion concentration and physiological levels of carbon dioxide and that it probably does not contribute significantly to formation of protein carbonyl derivatives or to the oxidation of methionine residues, both of which are widely used markers of oxidative protein damage. In continuing studies to identify major targets for peroxynitrite-dependent modification of proteins, the ability of peroxynitrite to nitrate tyrosine residues in bovine serum albumin (BSA) and glutamine synthetase (GS) was determined. Although these two proteins contain nearly identical numbers of tyrosine residues per subunit, they exhibit markedly different pH-dependent profiles of peroxynitrite-dependent nitration. It is thus evident that nitration of protein tyrosine residues is strongly dependent upon the molecular distribution of tyrosine residues and protein conformation. - peroxynitrite, protein carbonyls, peroxynitrite-carbon dioxide adducts