Kikugawa K, Kosugi H, Asakura T
Arch Biochem Biophys. 1984 Feb 15;229(1):7-14. doi: 10.1016/0003-9861(84)90124-3.
Malondialdehyde (MDA) was found to react with normal hemoglobin A (Hb A), forming a number of less cationic components which were detected by cellulose acetate electrophoresis and gel electrofocusing. All the modified components moved down the cation-exchange resin at a quicker rate than Hb A, and this chromatographic behavior of the modified components was similar to that of glycosylated Hb A. Some of these modified components were intermolecularly crosslinked, and showed fluorescence with an excitation maximum at 390 nm and an emission maximum at 460 nm. It is likely that MDA reacts nonspecifically with the epsilon-amino groups of lysine and N-terminal amino groups to produce aminoacrolein, crosslinks, and strongly fluorescent 1,4-dihydropyridine-3,5-dicarbaldehyde. Oxygen affinity of the modified hemoglobins was increased. The modified hemoglobins were more readily oxidized into met-form. Mechanical stability of Hb A was also decreased by the modification. These results suggest that a considerable conformational change in Hb A was induced by the treatment with MDA. Since MDA is generated in erythrocytes as a consequence of liquid peroxidation, MDA may react with intracellular Hb A and influence the function and the stability of hemoglobin.
发现丙二醛（MDA）与正常血红蛋白A（Hb A）反应，形成一些阳离子性较弱的组分，这些组分通过醋酸纤维素电泳和凝胶电聚焦检测。所有修饰后的组分在阳离子交换树脂上的移动速度比Hb A快，且修饰后组分的这种色谱行为与糖基化Hb A相似。其中一些修饰后的组分发生了分子间交联，并在激发波长最大值为390 nm、发射波长最大值为460 nm时显示出荧光。MDA可能与赖氨酸的ε-氨基和N-末端氨基发生非特异性反应，生成氨基丙烯醛、交联物以及强荧光的1,4-二氢吡啶-3,5-二甲醛。修饰后血红蛋白的氧亲和力增加。修饰后的血红蛋白更容易被氧化成高铁血红蛋白形式。修饰还降低了Hb A的机械稳定性。这些结果表明，MDA处理诱导了Hb A发生相当大的构象变化。由于MDA是红细胞中脂质过氧化的产物，MDA可能与细胞内的Hb A反应并影响血红蛋白的功能和稳定性。
