Iron nitrosyl hemoglobin formation from the reaction of hydroxylamine and hemoglobin under physiological conditions.
Iron nitrosyl hemoglobin formation from the reaction of hydroxylamine and hemoglobin under physiological conditions.
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生理条件下羟胺和血红蛋白反应形成亚硝酰铁血红蛋白。
DOI：
10.1016/j.bbagen.2004.07.003
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发表时间：
2004
期刊：
影响因子：
--
通讯作者：
King,SBruce
中科院分区：
文献类型：
--
作者：
Lockamy,VirginiaL;Shields,Howard;Kim-Shapiro,DanielB;King,SBruce
接受羟基脲（HU）治疗的镰状细胞病患者显示出一氧化氮（NO）代谢物的产生增加，所述代谢物包括铁亚硝基血红蛋白（HbNO）、亚硝酸盐和硝酸盐。然而，HU在体内形成HbNO的确切机制尚不清楚。先前的研究表明，氧合血红蛋白（oxyHb）或脱氧血红蛋白（deoxyHb）与HU的反应太慢，无法解释体内HbNO的产生。在这项研究中，我们表明，高铁血红蛋白（metHb）与HU形成HbNO的反应可能是足够快的占体内HbNO的形成，但在反应过程中过量的oxyHb或deoxyHb的竞争反应降低了HbNO将从metHb-HU反应产生的可能性。使用电子顺磁共振（EPR）光谱，我们已经检测到可测量的量的HbNO和metHb的oxyHb，deoxyHb，和metHb与过量的羟胺（HA）的反应过程中。我们还证明了HbNO和metHb形成过量的oxyHb，deoxyHb，或metHb和HA的反应，更有可能模仿那些在体内的条件。这些结果表明，羟胺与血红蛋白的反应产生HbNO，并为羟胺在体内代谢羟基脲中的潜在作用提供化学支持。
Sickle cell disease patients receiving hydroxyurea (HU) therapy have shown increases in the production of nitric oxide (NO) metabolites, which include iron nitrosyl hemoglobin (HbNO), nitrite, and nitrate. However, the exact mechanism by which HU forms HbNO in vivo is not understood. Previous studies indicate that the reaction of oxyhemoglobin (oxyHb) or deoxyhemoglobin (deoxyHb) with HU are too slow to account for in vivo HbNO production. In this study, we show that the reaction of methemoglobin (metHb) with HU to form HbNO could potentially be fast enough to account for in vivo HbNO formation but competing reactions of either excess oxyHb or deoxyHb during the reaction reduces the likelihood that HbNO will be produced from the metHb–HU reaction. Using electron paramagnetic resonance (EPR) spectroscopy we have detected measurable amounts of HbNO and metHb during the reactions of oxyHb, deoxyHb, and metHb with excess hydroxylamine (HA). We also demonstrate HbNO and metHb formation from the reactions of excess oxyHb, deoxyHb, or metHb and HA, conditions that are more likely to mimic those in vivo. These results indicate that the reaction of hydroxylamine with hemoglobin produces HbNO and lend chemical support for a potential role for hydroxylamine in the in vivo metabolism of hydroxyurea.