POST-TRANSLATIONALLY MODIFIED HEMOGLOBIN IN ALCOHOLISM

在大多数酗酒者中， 微量血红蛋白的形式显着高于正常。 雅阁 根据这一发现，酒精中毒的男性和女性的溶血产物被发现， 含有一种新形式的血红蛋白（血红蛋白Alalc，具有以下结构 特点：（1）与血红蛋白Alc共色谱， 阳离子交换树脂Biorex 70。 (2)它和血红蛋白一样， Alc，通过氨基苯基硼化琼脂糖，因此可以从 了 (3)对糖化血红蛋白不产生阳性反应 Fluckiger-Winterhalter测试。 血红蛋白一种血红蛋白， 类似于血红蛋白Alalc，含有1摩尔当量的 每摩尔血红蛋白中的乙醛被发现在溶血产物中， 用175 μ M（1- 3 H）孵育的人红细胞 乙醛 这和其他证据表明，血红蛋白Alalc是 后修饰的血红蛋白A，并且其由以下形成： 除了来自代谢的功能团的血红蛋白A之外 产生乙醛。 因此，该项目的主要目标是， 是为了阐明功能性的结构和连接部位， 将血红蛋白A转化为血红蛋白Alalc的基团，并阐明 乙酰丙酮衍生的修饰的结构和连接位点 血红蛋白Alald组。 为了实现这些目标， 并将应用成功建立路径的程序 以及血红蛋白Alc的形成机制。 血红蛋白Alalc 和Alald证明是相同的，从而直接关系到形成 血红蛋白Alalc酒精消费，它可能是可能的， 研究酗酒的发展与 酒精相关疾病，并使用血红蛋白Alalc的测量， 筛查隐性酗酒和酒精滥用 由于这些原因， 该项目还将涉及一个具体的发展， 血红蛋白Alalc的简易测定方法

In a majority of alcoholic indiviuals the proportion of hemoglobin in the form of minor hemoglobins is significantly greater than normal. In accord with this finding, hemolysates from alcoholic men and women were found to contain a novel form of hemoglobin (hemoglobin Alalc having the following characteristics: (1) It co-chromatographs with hemoglobin Alc on the cationic exchange resin Biorex 70. (2) It is not bound, as is hemoglobin Alc, by aminophenylboronated agarose and can therefore be separated from it. (3) It does not give a positive reaction for glycosylated hemoglobin by the Fluckiger-Winterhalter test. A form of hemoglobin having properties similar to hemoglobin Alalc and that contained 1 molar equivalent of acetaldehyde per mole of hemoglobin was found in hemolysates prepared from human erythrocytes that had been incubated with 175 MuM (1-3H) acetaldehyde. This and other evidence indicate that hemoglobin Alalc is post-translationally modified hemoglobin A and that it is formed by addition to hemoglobin A of a functional group derived from metabolically produced acetaldehyde. The chief objectives of this project, therefore, are to elucidate the structure and site of attachment of the functional group that transforms hemoglobin A to hemoglobin Alalc and to elucidate the structure and site of attachment of the acetaldehyde-derived modifying group in hemoglobin Alald. To accomplish these objectives the approaches and procedures will be applied that succeeded in establishing the pathway and mechanism of formation of hemoglobin Alc. Should hemoglobins Alalc and Alald prove to be identical, thus directly relating formation of hemoglobin Alalc to alcohol consumption, it may be possible to use that relationship to investigate the development of alcoholism and alcohol-related disorders and to use measurements of hemoglobin Alalc to screen for covert alcoholism and alcohol abuse. For these reasons this project will also concern itself with the development of a specific and simple method for the determination of hemoglobin Alalc.