Nitric oxide is consumed, rather than conserved, by reaction with oxyhemoglobin under physiological conditions
Nitric oxide is consumed, rather than conserved, by reaction with oxyhemoglobin under physiological conditions
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DOI：
10.1073/pnas.152149699
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发表时间：
2002-08-06
影响因子：
11.1
通讯作者：
Lancaster, JR
中科院分区：
文献类型：
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作者：
Joshi, MS;Ferguson, TB;Lancaster, JR
虽然NO与血红蛋白的氧血红素（产生硝酸盐和高铁血红蛋白）的不可逆反应非常迅速，但有人提出，在常氧条件下，NO优先与少数脱氧血红素结合，随后形成s -亚硝基血红蛋白（SNOHb）。因此，主要的反应是氮氧化物的保存，而不是消耗。支持这一结论的数据是通过向常氧血红蛋白溶液中加入少量的浓NO水溶液产生的。然而，在这些条件下，在混合之前会发生极快的反应。因此，我们比较了通过使用NO供体在整个溶液中均匀产生的NO，这是一种更生理相关的条件。在添加时，形成多种血红蛋白（通过可见光谱判断）以及亚硝酸盐和硝酸盐。在供体中，只形成硝酸盐和高铁血红蛋白，与从供体中释放的NO的数量成化学计量。血红蛋白浓度增加的研究表明，亚硝酸盐形成反应（在这些条件下可能是NO自氧化）与血红蛋白反应相竞争。SNOHb的形成可以通过药物或供体检测到；然而，形成的数量远小于添加NO的数量（小于1%）。我们得出结论，一氧化氮与血红蛋白的反应在常压条件下导致消耗，而不是保存，一氧化氮。
Although irreversible reaction of NO with the oxyheme of hemoglobin (producing nitrate and methemoglobin) is extremely rapid, it has been proposed that, under normoxic conditions, NO binds preferentially to the minority deoxyheme to subsequently form S-nitrosohemoglobin (SNOHb). Thus, the primary reaction would be conservation, rather than consumption, of nitrogen oxide. Data supporting this conclusion were generated by using addition of a small volume of a concentrated aqueous solution of NO to a normoxic hemoglobin solution. Under these conditions, however, extremely rapid reactions can occur before mixing. We have thus compared bolus NO addition to NO generated homogeneously throughout solution by using NO donors, a more physiologically relevant condition. With bolus addition, multiple hemoglobin species are formed (as judged by visible spectroscopy) as well as both nitrite and nitrate. With donor, only nitrate and methemoglobin are formed, stoichiometric with the amount of NO liberated from the donor. Studies with increasing hemoglobin concentrations reveal that the nitrite-forming reaction (which may be NO autoxidation under these conditions) competes with reaction with hemoglobin. SNOHb formation is detectable with either bolus or donor; however, the amounts formed are much smaller than the amount of NO added (less than 1%). We conclude that the reaction of NO with hemoglobin under normoxic conditions results in consumption, rather than conservation, of NO.