Herold S
Laboratorium für Anorganische Chemie, Eidgenössische Technische Hochschule, Universitätsstrasse 6, Zürich, CH-8092, Switzerland.
Arch Biochem Biophys. 1999 Dec 15;372(2):393-8. doi: 10.1006/abbi.1999.1534.
Pyridoxalated hemoglobin polyoxyethylene conjugate (PHP), a modified human-derived hemoglobin, is currently in clinical trials as a nitrogen monoxide scavenger for the treatment of shock. Stopped-flow spectroscopy studies of the reaction between nitrogen monoxide and PHP indicate that at pH 7 the second-order rate constant is (88 +/- 3) x 10(6) M(-1) s(-1), a value very similar to that for the unmodified human hemoglobin. At alkaline pH the reaction proceeds via the intermediate peroxynitrito complex PHP-Fe(III)OONO, which rapidly decomposes to nitrate and the iron(III) form of PHP. The rate of decay of PHP-Fe(III)OONO increases significantly with decreasing pH such that it does not accumulate in concentrations large enough to be observed spectroscopically under neutral or acidic conditions. Ion chromatographic analysis of the nitrogen-containing products of the NO(*)-mediated reaction of PHP shows that nitrate is formed quantitatively at both pH 7 and pH 9.
吡哆醛化血红蛋白聚氧乙烯共轭物（PHP）是一种经过修饰的人源血红蛋白，目前正作为一氧化氮清除剂进行治疗休克的临床试验。对一氧化氮与PHP之间反应的停流光谱研究表明，在pH值为7时，二级反应速率常数为(88±3)×10⁶ M⁻¹ s⁻¹，该值与未修饰的人血红蛋白非常相似。在碱性pH值下，反应通过中间产物过氧亚硝酸根复合物PHP-Fe(III)OONO进行，该复合物会迅速分解为硝酸盐和PHP的铁(III)形式。随着pH值降低，PHP-Fe(III)OONO的衰变速率显著增加，以至于在中性或酸性条件下，它不会积累到足以通过光谱观察到的浓度。对PHP的NO介导反应的含氮产物进行离子色谱分析表明，在pH值为7和pH值为9时均定量形成硝酸盐。
