Ueno H, Manning J M
Rockefeller University, New York, NY 10021.
Am J Pediatr Hematol Oncol. 1988 Winter;10(4):348-50. doi: 10.1097/00043426-198824000-00017.
Methyl acetyl phosphate inhibits the sickling of erythrocytes in vitro. Its mechanism of action is through the selective acetylation of some of the amino groups at the 2,3-diphosphoglycerate (2,3-DPG) binding site of the hemoglobin molecule. Only 3 of a total 24 amino groups per alpha beta-dimer of hemoglobin are reactive. These groups are Val-1, Lys-82, and Lys-144 on the beta-chain of hemoglobin. None of the groups on the alpha-chain are acetylated. Acetylated hemoglobin S has an increased solubility as well as a reduced ability to bind to 2,3-DPG. Methyl acetyl phosphate is able to penetrate the erythrocyte membrane and successfully acetylate intracellular hemoglobin S without causing cell lysis. Sickle erythrocytes treated with methyl acetyl phosphate maintain an oxy-like profile of cell density distribution in a phthalate ester gradient. The oxygen binding property of erythrocytes after the treatment with methyl acetyl phosphate is not changed significantly from that of untreated cells. Our in vitro results indicate that further preclinical testing of methyl acetyl phosphate in sickle cell anemia is warranted.
甲基乙酰磷酸在体外可抑制红细胞镰变。其作用机制是通过对血红蛋白分子2,3 - 二磷酸甘油酸（2,3 - DPG）结合位点的一些氨基进行选择性乙酰化。每αβ - 二聚体血红蛋白总共24个氨基中只有3个具有反应活性。这些基团是血红蛋白β链上的缬氨酸 - 1、赖氨酸 - 82和赖氨酸 - 144。α链上的基团均未被乙酰化。乙酰化的血红蛋白S溶解度增加，与2,3 - DPG结合的能力降低。甲基乙酰磷酸能够穿透红细胞膜并成功使细胞内的血红蛋白S乙酰化，而不会导致细胞裂解。用甲基乙酰磷酸处理的镰状红细胞在邻苯二甲酸酯梯度中保持类似氧合状态的细胞密度分布。用甲基乙酰磷酸处理后红细胞的氧结合特性与未处理细胞相比没有明显变化。我们的体外研究结果表明，甲基乙酰磷酸在镰状细胞贫血中的进一步临床前试验是有必要的。
