Cho S-J, Roman G, Yeboah F, Konishi Y
National Research Council Canada, Biotechnology Research Institute, 6100 Royalmount Ave., Montréal, QC, H4P 2R2, Canada.
Curr Med Chem. 2007;14(15):1653-71. doi: 10.2174/092986707780830989.
Protein glycation is a slow natural process involving the chemical modification of the reactive amino and guanidine functions in amino acids by sugars and carbohydrates-derived reactive carbonyls. Its deleterious consequences are obvious in the case of long-lived proteins in aged people and are exacerbated by the high blood concentration of sugars in diabetic patients. The non-enzymatic glycation of proteins occurs through a wide range of concurrent processes comprising condensation, rearrangement, fragmentation, and oxidation reactions. Using a few well established intermediates such as Schiff base, Amadori product and reactive a-dicarbonyls as milestones and the results of in vitro glycation investigations, an overall detailed mechanistic analysis of protein glycation is presented for the first time. The pathways leading to several advanced glycation end products (AGEs) such as (carboxymethyl)lysine, pentosidine, and glucosepane are outlined, whereas other AGEs useful as potential biomarkers of glycation are only briefly mentioned. The current stage of the development of glycation inhibitors has been reviewed with an emphasis on their mechanism of action.
蛋白质糖基化是一个缓慢的自然过程，涉及糖类和碳水化合物衍生的活性羰基对氨基酸中反应性氨基和胍基的化学修饰。在老年人中，对于长寿蛋白而言，其有害后果是显而易见的，而糖尿病患者血液中高糖浓度会加剧这种情况。蛋白质的非酶糖基化通过多种同时发生的过程进行，包括缩合、重排、碎片化和氧化反应。本文首次以席夫碱、阿马多里产物和活性α - 二羰基等一些成熟的中间体为里程碑，并结合体外糖基化研究结果，对蛋白质糖基化进行了全面详细的机理分析。文中概述了导致几种晚期糖基化终产物（AGEs）如（羧甲基）赖氨酸、戊糖苷和葡糖醛酸苷的途径，而其他可用作糖基化潜在生物标志物的AGEs仅作了简要提及。本文对糖基化抑制剂的当前发展阶段进行了综述，重点介绍了它们的作用机制。
