Chace K V, Carubelli R, Nordquist R E
Dean A. McGee Eye Institute, Oklahoma City, OK 73104.
Arch Biochem Biophys. 1991 Aug 1;288(2):473-80. doi: 10.1016/0003-9861(91)90223-6.
Incubation of corneal collagen type I with glucose in the presence of transition metal ions (copper, iron) results in the formation of collagen aggregates insoluble in 6 M urea, and in 2% sodium dodecyl sulfate + 5% beta-mercaptoethanol. The reaction is mediated by hydrogen peroxide and transition metals since it is inhibited by catalase and by the chelating agent diethylenetriaminepentaacetic acid. Comparative studies showed that copper is more efficient than iron and that the reaction proceeds more rapidly with ribose than with glucose. The data support a mechanism involving transition metal ion catalyzed autoxidation of glucose (and possibly of Amadori products) with generation of superoxide radical. Superoxide dismutation produces hydrogen peroxide, which then generates hydroxyl radicals in the presence of transition metal ions (Fenton reaction). Hydroxyl radical attack is known to lead to cross-linking, which is enhanced in glycated proteins. The experimental data presented are consistent with in vivo alteration of collagen properties during normal aging and with the acceleration of similar changes in diabetes mellitus.
在过渡金属离子（铜、铁）存在的情况下，将角膜I型胶原蛋白与葡萄糖一起孵育，会导致形成不溶于6M尿素以及2%十二烷基硫酸钠+5%β-巯基乙醇的胶原蛋白聚集体。该反应由过氧化氢和过渡金属介导，因为它受到过氧化氢酶和螯合剂二乙烯三胺五乙酸的抑制。比较研究表明，铜比铁更有效，并且该反应与核糖反应比与葡萄糖反应进行得更快。这些数据支持一种机制，即涉及过渡金属离子催化葡萄糖（可能还有阿马多里产物）的自氧化并产生超氧自由基。超氧化物歧化产生过氧化氢，然后过氧化氢在过渡金属离子存在的情况下产生羟基自由基（芬顿反应）。已知羟基自由基攻击会导致交联，这在糖化蛋白质中会增强。所呈现的实验数据与正常衰老过程中胶原蛋白特性的体内改变以及糖尿病中类似变化的加速一致。
