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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Peroxynitrite-mediated modification of proteins at physiological carbon dioxide concentration: pH dependence of carbonyl formation, tyrosine nitrtion, and methionine oxidation
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Peroxynitrite-mediated modification of proteins at physiological carbon dioxide concentration: pH dependence of carbonyl formation, tyrosine nitrtion, and methionine oxidation

机译:在生理二氧化碳浓度下过氧亚硝酸盐介导的蛋白质修饰:pH依赖于羰基形成,酪氨酸硝化和蛋氨酸氧化

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The ability of peroxynitrite to modifyamino acid residues in glutamine synthetase (GS) and BSA is greatly influenced by pH and CO2. At physiological concentration of CO2 (1.3 mM), the generation of carbonyl groups (0.2-0.4) equivalents/subunit) is little affected by pH over the range of 7.2-9.0, but, in the absence of CO2, carbonyl formation increases (rom 0.1-1.2 equivalents/subunit) as the pH is raised from 7.2 to 10.5. This increase is attributable, in part but not entirely, to the increase in peroxynitrite (PN) stability with increasing pH. Of several amino acid polymers tested, only those containing lysine residues yielded carbonyl derivatives In contrast, the nitration of tyrosine residues of both GS and BSA at pH 7.5 almost completely depends on the presence of CO2 . However, the pH profiles of tyrosine nitration in GS and BSA are not the same. With both proteins, nitration decreases approximately equals 65/100 with increasing pH over the range of 7.2-8.4, but then in the case of GS only, ,there is a 3.4-fold increase in the level of nitration over the range pH 8.4-8.8. The oxidation of methionine residues in both proteins and in the tripeptide Ala-Met-Ala was inhibited by CO2 at both high and low pH values. These results emphasize the importance of controlling the pH and CO2 concentrations in studies invelving PN and indicate that PN is not likely to contribute appreciably to carbonyl formation or oxidation of methionine residues of proteins at physiological pH and CO2 cencentrations.
机译:过氧亚硝酸盐修饰谷氨酰胺合成酶(GS)和BSA中氨基酸残基的能力受pH和CO2的影响很大。在生理浓度的CO2(1.3 mM)下,pH在7.2-9.0范围内对羰基基团(0.2-0.4)当量/亚基的生成几乎没有影响,但是,在没有CO2的情况下,羰基的形成会增加(rom pH值从7.2提高到10.5时为0.1-1.2当量/亚基)。这种增加部分地但不是全部地归因于过亚硝酸盐(PN)稳定性随pH值的增加而增加。在测试的几种氨基酸聚合物中,只有那些含有赖氨酸残基的氨基酸聚合物才能生成羰基衍生物。相反,GS和BSA在pH 7.5时酪氨酸残基的硝化几乎完全取决于CO2的存在。但是,GS和BSA中酪氨酸硝化的pH值不同。对于这两种蛋白质,在7.2-8.4范围内,随着pH值的增加,硝化作用降低约等于65/100,但是仅在GS的情况下,在8.4-pH范围内,硝化作用水平增加了3.4倍。 8.8。在高和低pH值下,CO2均会抑制蛋白质和三肽Ala-Met-Ala中蛋氨酸残基的氧化。这些结果强调了在研究PN的研究中控制pH和CO2浓度的重要性,并表明在生理pH和CO2浓度下,PN不太可能显着促进蛋白质的蛋氨酸残基的羰基形成或氧化。

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