ASCORBIC ACID GLYCATION AND SENILE CATARACT FORMATION

在透镜蛋白的糖基化作为一种生物学行为方面有相当大的兴趣。 糖尿病和老年性白内障的发病机制。长的一半 透镜蛋白质的寿命预测糖化分子应该积累 在透镜中，并可能在高分子的形成中发挥作用。 老年晶状体和白内障中的蛋白质聚集体。经过10年 在研究中，识别方面几乎没有进展， 糖化产物定量，无蛋白质直接证据 交联即将到来。我们一直在研究透镜的糖化 蛋白质由抗坏血酸而不是葡萄糖。当抗坏血酸 氧化为脱氢抗坏血酸，发生快速糖化和交联 其类似于白内障中所见。特定的氨基酸加合物具有 被分离出来，其中几个是目前在相对较高的 在来自人透镜组织的水不溶性部分中的浓度。我们 我打算在这里概述的工作中获得更确切的数据， 抗坏血酸降解产物的鉴定及降解速率的研究 在存在于透镜中的条件下形成每一个。的 计划分离和鉴定5种不同的赖氨酸加合物， 以及它们作为白内障提取物中的修饰氨基酸的鉴定。 还将采取几种方法，试图确定 晶体蛋白之间形成的交联。实验还设计了 看看抗坏血酸是否能在无氧的产生中发挥作用， 自由基，并估计这是否是一个可行的机制， 体内蛋白质损伤。

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.