ASCORBIC ACID GLYCATION & SENILE CATARACT FORMATION

蛋白质的非酶糖基化代表了一种缓慢的 在血清中连续进行的修饰反应， 组织中 该反应被称为美拉德反应， 越来越受到关注，因为它可能是许多 在糖尿病期间观察到的后遗症。 它是已知的 初始碳水化合物-蛋白质加合物经历一系列复杂的 化学反应，最终会导致 1)蛋白质-蛋白质交联，2）各种蛋白质结合 发色团和3）产生蓝色的复杂分子 当用紫外光照射时，荧光。 这些 次级反应在透镜组织中可能是非常重要的， 因为透镜表现出很少或没有蛋白质周转， 透镜核可能在整个生命过程中都存在。 因为它 已知老年性白内障晶状体确实含有交联的 蛋白质以及蛋白质结合的发色团和荧光团 与糖基化产生的那些类似， 美拉德反应的产物可能是 在白内障形成中。 这种反应被认为仅限于 然而，最近显示抗坏血酸是 也能够通过美拉德反应修饰透镜蛋白。 抗坏血酸的浓度较高， 与透镜蛋白质的反应比葡萄糖，但很少有人知道 抗坏血酸蛋白质加合物的化学。 工作 将进行分离和鉴定， 抗坏血酸和模型α-N之间形成的产物 封闭的氨基酸。 这些结果将与 通过体外修饰透镜晶体蛋白生产的产品 以及从人透镜中分离的产物 proteins. α-晶状体蛋白的特异性修饰位点 将被识别，此外，这些影响 对α-晶状体蛋白性质的修饰将是 研究了 将进行初步实验， 描述了由孵育诱导的蛋白质交联的性质， 透镜晶体蛋白与抗坏血酸在生理条件下。

The non-enzymatic glycosylation of proteins represents a slow modification reaction which proceeds continuously in serum and in tissues. This reaction is termed the Maillard reaction and is receiving increasing attention as it may be responsible for many of the sequelae observed during diabetes. It is known that the initial carbohydrate-protein adducts undergo a complex series of chemical reactions, which can ultimately cause the production of 1) protein-protein crosslinks, 2) a variety of protein-bound chromophores and 3) complex molecules which produce a blue fluorescence when irradiated with ultraviolet light. These secondary reactions are likely to be very important in lens tissue, because lens exhibits little or no protein turnover, and proteins in the lens nucleus may have been present throughout life. Since it is known that senile cataractous lenses do contain crosslinked proteins as well as protein-bound chromophores and fluorophores similar to those produced by glycosylation, it has been suggested that the products of the Maillard reaction may be a major factor in cataractogenesis. This reaction was thought to be limited to glucose, however, it has been recently shown that ascorbic acid is also capable of modifying lens proteins via the Maillard reaction. Ascorbic acid is present in higher concentrations and is more reactive with lens proteins than glucose, yet little is known about the chemistry of ascorbic acid protein adducts. The work described here will be undertaken to isolate and identify the products formed between ascorbic acid and model alpha-N blocked amino acids. These results will be compared to the products produced by the in vitro modification of lens crystallins by ascorbic acid and to products isolated from human lens proteins. The specific sites of modification in alpha-crystallin will be identified, and in addition the effects of these modifications on the properties of alpha-crystallin will be investigated. Preliminary experiments will be carried out to describe the nature of the protein crosslinks induced by incubating lens crystallins with ascorbic acid under physiological conditions.