Acetaldehyde adducts with hemoglobin.

Acetaldehyde adducts with hemoglobin.
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乙醛与血红蛋白的加合物。

DOI:
10.1172/jci110043
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发表时间:
1981
期刊:
The Journal of clinical investigation
影响因子:
--
通讯作者:
Peterson,CM
Peterson,CM
中科院分区:
--
文献类型:
--
作者:
Stevens,VJ;Fantl,WJ;Newman,CB;Sims,RV;Cerami,A;Peterson,CM

文献摘要

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对次要血红蛋白(血红蛋白A1 a-c)的临床研究表明,滥用酒精的人可能会形成一种新的加合物。发现这些患者的次要血红蛋白浓度升高,但通过放射免疫测定法测定的糖化血红蛋白(血红蛋白A1 c)含量正常或低于正常水平。乙醛是乙醇的反应性代谢产物,被假定与血红蛋白A形成加合物,改变其色谱特性。在生理浓度下,发现乙醛与血红蛋白形成加合物,这些加合物对几天的广泛透析是稳定的。形成的血红蛋白加合物的量是暴露于乙醛的浓度和次数的函数。乙醛与血红蛋白A的反应产生色谱变体,其中一些迁移到血红蛋白A1 a-c区域。稳定的乙酰化血红蛋白加合物的分析表明,球蛋白的缬氨酸,赖氨酸和酪氨酸残基的反应位点。乙酰丙酮修饰的氨基酸残基似乎存在于相互转换的构象,其中只有一个是可还原的硼氢化钠。与正常志愿者相比,酗酒者血红蛋白中这些加合物的含量显著升高。
Clinical studies on the minor hemoglobins (hemoglobin A1a-c) have suggested that a novel adduct may form in people abusing alcohol. Such patients were found to have an elevated concentration of minor hemoglobins, but normal or subnormal amounts of glycosylated hemoglobin (hemoglobin A1c) as determined by radioimmunoassay, Acetaldehyde, a reactive metabolite of ethanol, was postulated to form adducts with hemoglobin A that change its chromatographic properties. At physiological concentrations, acetaldehyde was found to form adducts with hemoglobin that were stable to extensive dialysis for several days. The amount of hemoglobin adducts formed were a function of the concentration and number of exposures to acetaldehyde. The reaction of acetaldehyde with hemoglobin A produced chromatographic variants, some of which migrated in the hemoglobin A1a-c region. Analysis of stable acetaldehyde-hemoglobin adducts demonstrated that valine, lysine, and tyrosine residues of globin were sites of reaction. The acetaldehyde-modified amino acid residues appear to exist in interconvertible conformations, only one of which is reducible by sodium borohydride. The amount of these adducts was found to be significantly elevated in hemoglobin from alcoholics as compared with normal volunteers.