ASCORBIC ACID GLYCATION AND SENILE CATARACT FORMATION

人们对晶状体蛋白质的糖基化作为一种 糖尿病和老年性白内障的发病机制。长长的一半 晶状体蛋白质的寿命预测糖化分子应该积累 在晶状体中，并可能起到形成高分子结构的作用 老化晶状体和白内障中可见的重量蛋白质聚集体。十年后 在研究方面，在识别和识别方面进展甚微 糖化产物的定量，没有蛋白质的直接证据 交联剂即将问世。我们一直在研究晶状体的糖基化 蛋白质由抗坏血酸而不是葡萄糖组成。当抗坏血酸 氧化成脱氢抗坏血酸，发生快速糖基化和交联化 这与白内障中的情况相似。特定的氨基酸加合物有 已经被隔离，其中几个目前处于相对较高的水平 人晶状体组织中水不溶部分的浓度。我们 打算在这里概述的工作中获得更明确的数据 抗坏血酸降解产物的鉴定及降解速率研究 在晶状体中存在的条件下形成的每一个。这个 计划分离和鉴定5种不同的赖氨酸加合物，如 以及它们在白内障提取物中作为修饰氨基酸的鉴定。 还将采取几种方法来尝试确定其性质 晶体蛋白之间形成的交联键。还设计了实验 看看抗坏血酸是否能在氧自由基的产生中发挥作用 并估计这是否是一个可行的机制，以增加 体内的蛋白质损伤。

There has been considerable interest in the glycation of lens proteins as a causative mechanism of both diabetic and senile cataract. The long half life of the lens proteins predict that glycated molecules should accumulate in the lens, and may play a role in the formation of the high molecular weight protein aggregates seen in aged lenses and cataracts. After 10 years of research there has been little progress on identification and quantitation of glycated products, and no direct evidence for protein crosslinking has been forthcoming. We have been studying glycation of lens proteins by ascorbic acid as opposed to glucose. When ascorbic acid is oxidized to dehydroascorbic acid, a rapid glycation and crosslinking occurs which resembles that seen in cataract. Specific amino acid adducts have been isolated, and several of these are present at relatively high concentrations in the water-insoluble fraction from human lens tissue. We intend to obtain more definitive data in the work outlined here by identifying the degradation products of ascorbic acid and studying the rate of formation of each under the conditions present in the lens. The isolation and identification of 5 different lysine adducts is planned, as well as their identification as modified amino acids in cataract extracts. Several approaches will also be taken in an attempt to identify the nature of the crosslink formed between crystallins. Experiments are also designed to see if ascorbic acid can play a role in the generation of oxygen free radicals, and to estimate whether this is a viable mechanism for additional protein damage in vivo.