POST-TRANSLATIONALLY MODIFIED HEMOGLOBIN IN ALCOHOLISM

在大多数酗酒者中，血红蛋白在 形态较少的血红蛋白明显大于正常。一致的 根据这一发现，酗酒的男性和女性的溶血物被发现 含有一种新形式的血红蛋白(具有以下特性的血红蛋白Alalc 特点：(1)与血红蛋白Alc共层析 阳离子交换树脂Biorex 70。(2)它没有结合，就像血红蛋白一样 Alc，通过氨基苯基硼化琼脂糖化，因此可以从 它。(3)糖化血红蛋白不呈阳性反应。 通过FLuckiger-Winterhalter测试。一种具有某些特性的血红蛋白 与血红蛋白Alalc相似，且含有1摩尔当量的 在由乙醛制成的溶血物中，发现每摩尔血红蛋白含有乙醛。 与175微米(1-3 H)孵育的人红细胞 乙醛。这一证据和其他证据表明，血红蛋白Alalc 翻译后修饰的血红蛋白A和它是由 加成来自代谢衍生的官能团的血红蛋白A 产生乙醛。因此，这个项目的主要目标是， 是为了阐明功能细胞的附着结构和位置 将Hb A转化为Hb Alc的基团，并阐明 乙醛基改性剂的结构和附着位置 血红蛋白Alald组。为了实现这些目标，这些方法 并将应用成功建立该途径的程序 和血红蛋白Alc的形成机制。血红蛋白应该是Alalc吗 和Alald被证明是相同的，因此直接与 血红蛋白Alalc对饮酒来说，可能是可以使用的 研究酒精中毒的发展与 酒精相关疾病和使用测量血红蛋白Alalc来 筛查隐蔽的酗酒和酗酒行为。出于这些原因， 项目本身也将关注一个具体的和 一种简便的测定血红蛋白的方法。

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.