Green F A, Jung C Y, Rampal A, Lorusso D J
Clin Exp Immunol. 1980 Jun;40(3):554-60.
Alpha-methyldopa binds to human erythrocyte membrane proteins. A portion of this binding is readily dissociable in SDS but a significant amount is very tightly bound and does not come off even under rigorous conditions. The binding is increased under oxidizing conditions and very much inhibited in the presence of reducing agents as well as superoxide dismutase and catalase. Haemoglobin competes with membrane peptides for alpha-methyldopa binding. It is postulated that haemoglobin acts as a 'sink' for the drug in the intact cell and that the first step in the pathogenesis of Coombs positivity and haemolytic anaemia results from an alteration of a critical membrane peptide secondary to binding of the drug during normal membrane breakdown.
α-甲基多巴与人类红细胞膜蛋白结合。这种结合的一部分在十二烷基硫酸钠(SDS)中很容易解离,但相当一部分结合非常紧密,即使在严格条件下也不会脱落。在氧化条件下结合增加,在还原剂、超氧化物歧化酶和过氧化氢酶存在时结合受到很大抑制。血红蛋白与膜肽竞争α-甲基多巴的结合。据推测,在完整细胞中血红蛋白充当药物的“汇”,而库姆斯阳性和溶血性贫血发病机制的第一步是由于在正常膜破裂过程中药物结合导致关键膜肽改变所致。