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Reactions between nitric oxide and haemoglobin under physiological conditions.

机译:一氧化氮与血红蛋白在生理条件下的反应。

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The tenet of high-affinity nitric oxide (NO) binding to a haemoglobin (Hb) has shaped our view of haem proteins and of small diffusible signaling molecules. Specifically, NO binds rapidly to haem iron in Hb (k approximately 10[7] M[-1] s[-1]) and once bound, the NO activity is largely irretrievable (Kd approximately 10[-5] s[-1]); the binding is purportedly so tight as to be unaffected by O2 or CO. However, these general principles do not consider the allosteric state of Hb or the nature of the allosteric effector, and they mostly derive from the functional behaviour of fully nitrosylated Hb, whereas Hb is only partially nitrosylated in vivo. Here we show that oxygen drives the conversion of nitrosylhaemoglobin in the 'tense' T (or partially nitrosylated, deoxy) structure to S-nitrosohaemoglobin in the 'relaxed' R (or ligand-bound, oxy) structure. In the absence of oxygen, nitroxyl anion (NO-) is liberated in a reaction producing methaemoglobin. The yields of both S-nitrosohaemoglobin and methaemoglobin are dependent on the NO/Hb ratio. These newly discovered reactions elucidate mechanisms underlying NO function in the respiratory cycle, and provide insight into the aetiology of S-nitrosothiols, methaemoglobin and its related valency hybrids. Mechanistic reexamination of NO interactions with other haem proteins containing allosteric-site thiols may be warranted.
机译:高亲和力一氧化氮(NO)与血红蛋白(Hb)结合的宗旨塑造了我们对血红蛋白和小的可扩散信号分子的看法。具体而言,NO迅速结合到血红蛋白中的血红素铁中(k约为10 [7] M [-1] s [-1]),一旦结合,则NO活性几乎无法恢复(Kd约为10 [-5] s [-1) ]);据称,结合是如此紧密,以至于不受O2或CO的影响。但是,这些一般原则并未考虑Hb的变构状态或变构效应物的性质,它们主要源自完全亚硝化Hb的功能行为,而Hb在体内仅被部分亚硝化。在这里,我们显示氧气驱动“紧张” T(或部分亚硝基化的脱氧)结构中的亚硝基血红蛋白转化为“松弛” R(或与配体结合的氧基)中的S-亚硝基血红蛋白。在不存在氧气的情况下,会在生成甲基血红蛋白的反应中释放出硝酰阴离子(NO-)。 S-亚硝基血红蛋白和高铁血红蛋白的产率均取决于NO / Hb比。这些新发现的反应阐明了呼吸循环中NO功能的潜在机制,并提供了对S-亚硝基硫醇,血红蛋白及其相关化合价杂物的病因学的见解。可能需要对与其他含有变构位点巯基的血红素蛋白的相互作用进行机械的重新检查。

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