Tuma D J, Jennett R B, Sorrell M F
Ann N Y Acad Sci. 1987;492:277-86. doi: 10.1111/j.1749-6632.1987.tb48681.x.
Acetaldehyde covalently binds to purified tubulin in vitro to form both stable and unstable adducts. The formation of stable adducts can be greatly facilitated by the inclusion of the relatively gentle and Schiff base specific reducing agent, sodium cyanoborohydride. Although the tubulin molecule has multiple lysine resides available to react with acetaldehyde, certain key lysine residues on the alpha-chain appear to be selective targets for adduct formation. The formation of alpha-chain specific stable acetaldehyde-tubulin adducts results in functional impairment of the ability of tubulin to polymerize. Under relatively physiologic conditions where acetaldehyde-to-protein ratios are low, alpha-chain specific binding is prominent. These results, coupled with the studies presented in another report in this volume, raise the possibility that low levels of adduct formation may be detrimental to the structure or function of certain proteins (e.g. tubulin) in the liver. The alteration of this or other biologically important proteins by sustained low levels of adduct formation may contribute to the pathogenesis of alcoholic liver injury.
乙醛在体外与纯化的微管蛋白共价结合，形成稳定和不稳定的加合物。加入相对温和且对席夫碱具有特异性的还原剂氰基硼氢化钠，可极大地促进稳定加合物的形成。尽管微管蛋白分子有多个赖氨酸残基可与乙醛反应，但α链上的某些关键赖氨酸残基似乎是加合物形成的选择性靶点。α链特异性稳定乙醛 - 微管蛋白加合物的形成导致微管蛋白聚合能力的功能受损。在乙醛与蛋白质比例较低的相对生理条件下，α链特异性结合很突出。这些结果，再加上本卷另一篇报告中的研究，增加了低水平加合物形成可能对肝脏中某些蛋白质（如微管蛋白）的结构或功能有害的可能性。持续低水平的加合物形成对这种或其他生物学重要蛋白质的改变可能有助于酒精性肝损伤的发病机制。
