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通过甲基乙酰磷酸选择性乙酰化抑制细胞外和细胞内血红蛋白S的凝胶化。

Inhibition of the gelation of extracellular and intracellular hemoglobin S by selective acetylation with methyl acetyl phosphate.

作者信息

Ueno H, Benjamin L J, Pospischil M A, Manning J M

出版信息

Biochemistry. 1987 Jun 2;26(11):3125-9. doi: 10.1021/bi00385a027.

Abstract

Methyl acetyl phosphate binds to the 2,3-diphosphoglycerate (2,3-DPG) binding site of hemoglobin and selectively acetylates three amino groups at or near that site. The subsequent binding of 2,3-DPG is thus impeded. When intact sickle cells are exposed to methyl acetyl phosphate, their abnormally high density under anaerobic conditions is reduced to the density range of oxygenated, nonsickling erythrocytes. This change is probably due to a combination of direct and indirect effects induced by the specific acetylation. The direct effect is on the solubility of deoxyhemoglobin S, which is increased from 17 g/dL for unmodified hemoglobin S to 22 g/dL for acetylated hemoglobin S at pH 6.8. Acetylated hemoglobin S does not gel at pH 7.4, up to a concentration of 32 g/dL. The indirect effect could be due to the decreased binding of 2,3-DPG to deoxyhemoglobin S within the sickle erythrocyte, thus hindering the conversion of oxyhemoglobin S to the gelling form, deoxyhemoglobin S.

摘要

甲基乙酰磷酸与血红蛋白的2,3 - 二磷酸甘油酸(2,3-DPG)结合位点结合,并选择性地乙酰化该位点或其附近的三个氨基。因此,随后2,3-DPG的结合受到阻碍。当完整的镰状细胞暴露于甲基乙酰磷酸时,它们在厌氧条件下异常高的密度会降低到氧合的、非镰状红细胞的密度范围。这种变化可能是由于特定乙酰化诱导的直接和间接效应的综合作用。直接效应是对脱氧血红蛋白S的溶解度产生影响,在pH 6.8时,未修饰的血红蛋白S的溶解度为17 g/dL,而乙酰化血红蛋白S的溶解度增加到22 g/dL。在pH 7.4时,浓度高达32 g/dL的乙酰化血红蛋白S不会形成凝胶。间接效应可能是由于镰状红细胞内2,3-DPG与脱氧血红蛋白S的结合减少,从而阻碍了氧合血红蛋白S向凝胶形式的脱氧血红蛋白S的转化。

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