The reaction between nitrite and deoxyhemoglobin - Reassessment of reaction kinetics and stoichiometry
The reaction between nitrite and deoxyhemoglobin - Reassessment of reaction kinetics and stoichiometry
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DOI：
10.1074/jbc.m501496200
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发表时间：
2005-09-02
影响因子：
4.8
通讯作者：
Hogg, N
中科院分区：
文献类型：
--
作者：
Huang, KT;Keszler, A;Hogg, N
最近的证据表明，亚硝酸盐和脱氧血红蛋白之间的反应提供了体内合成一氧化氮的机制。该反应先前已被定义为遵循二级动力学，尽管已经报道了可变的产物化学计量。在这项研究中，我们重新检查了该反应，发现在完全脱氧条件下，产物化学计量比为1：1（高铁血红蛋白：亚硝基血红蛋白），出乎意料的是，动力学与简单的二级反应有很大差异，并表现出S形曲线。该反应的动力学与血红素氧化和铁亚硝基化引起的反应速率增加一致。此外，有利于“R”构象的条件显示出比有利于“T”构象的条件增加的速率。亚硝酸盐与血红素的反应性显然比以前认识到的更复杂，并且取决于血红蛋白四聚体的构象状态，这表明血红蛋白的亚硝酸盐还原酶活性是在变构控制下的。
Recent evidence suggests that the reaction between nitrite and deoxygenated hemoglobin provides a mechanism by which nitric oxide is synthesized in vivo. This reaction has been previously defined to follow second order kinetics, although variable product stoichiometry has been reported. In this study we have re-examined this reaction and found that under fully deoxygenated conditions the product stoichiometry is 1: 1 ( methemoglobin: nitrosylhemoglobin), and unexpectedly, the kinetics deviate substantially from a simple second order reaction and exhibit a sigmoidal profile. The kinetics of this reaction are consistent with an increase in reaction rate elicited by heme oxidation and iron-nitrosylation. In addition, conditions that favor the "R" conformation show an increased rate over conditions that favor the "T" conformation. The reactivity of nitrite with heme is clearly more complex than has been previously realized and is dependent upon the conformational state of the hemoglobin tetramer, suggesting that the nitrite reductase activity of hemoglobin is under allosteric control.