Protein glycation - Creation of catalytic sites for free radical generation
Protein glycation - Creation of catalytic sites for free radical generation
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DOI：
10.1111/j.1749-6632.2001.tb05634.x
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发表时间：
2001-01-01
期刊：
影响因子：
--
通讯作者：
Chock, PB
中科院分区：
文献类型：
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作者：
Yim, MB;Yim, HS;Chock, PB
在糖化反应中，α-二羰基化合物如脱氧葡糖醛酮、甲基乙二醛和乙二醛在与蛋白质的氨基反应以形成蛋白质的分子间和分子内交联、称为高级美拉德产物或高级终产物（AGE）的稳定终产物的能力方面比母体糖更具反应性。AGES是不可逆形成的，随着衰老、动脉粥样硬化和糖尿病而积累，特别是与长寿蛋白如胶原、透镜蛋白和神经蛋白有关。提示AGEs的形成不仅改变蛋白质的性质，而且在体内引起生物学损伤。在本报告中，我们总结了我们的研究获得的结果：（1）鉴定模型系统中形成的交联自由基物质的结构-α-二羰基甲基乙二醛与氨基酸之间的反应，以及（2）自由基中心的反应性类似反应产生的蛋白质。这些结果表明，蛋白质的糖基化产生催化单电子氧化还原反应的活性中心。这个活性中心，它表现出酶样的字符，被认为是交联的希夫基自由基阳离子的蛋白质。它模仿了金属催化氧化体系的特征。这些结果共同表明，在体内积累的糖化蛋白质为催化自由基的形成提供了稳定的活性位点。
In a glycation reaction, alpha -dicarbonyl compounds such as deoxyglucosone, methylglyoxal, and glyoxal are more reactive than the parent sugars with respect to their ability to react with amino groups of proteins to form inter-and intramolecular cross-links of proteins, stable end products called advanced Maillard products or advanced end products (AGEs). The AGES, which are irreversibly formed, accumulate with aging, atherosclerosis, and diabetes mellitus, and are especially associated with long-lived proteins such as collagens, lens crystallins, and nerve proteins. It was suggested that the formation of AGEs not only modifies protein properites but also induces biological damage in vivo. In this report, we summerize results obtained from our studies for (1) identifying the structure of the cross-linked radical species formed in the model system-the reaction between alpha -dicarbonyl methylglyoxal with amino acids, and (2) the reactivity of the radical center of the protein created by the similar reaction. These results indicate that glycation of protein generates active centers for catalyzing one-electron oxidation-reduction reactions. This active center, which exhibits enzyme-like character, is suggested to be the crosslinked Schiff-based radical cation of the protein. It mimics the characteristics of the metal-catalyzed oxidation system. These results together indicate that glycated proteins accumulated in vivo provide stable active sites for catalyzing the formation of free redicals.