Lapolla Annunziata, Fedele Domenico, Seraglia Roberta, Traldi Pietro
Dipartimento di Scienze Mediche e Chirurgiche, Cattedra di Malattie del Metabolismo, Università di Padova, Padova, Italy.
Mass Spectrom Rev. 2006 Sep-Oct;25(5):775-97. doi: 10.1002/mas.20090.
Recent studies on non-enzymatic protein glycation are reviewed, and results are critically discussed. Advanced glycation end products (AGE) levels in the body reflect a balance between their formation and catabolism. AGE proteolysis leads to the formation of low-molecular-weight AGE (AGE peptides) that are normally excreted in urine. In the case of diabetic disease and/or renal failure, AGE peptides accumulate in plasma. Because of their high reactivity, these compounds have been thought to play a role in the progression of chronic complications. The structural identification of these compounds is particularly important, and a strategy has been designed for their possible definition. A series of experiments has been devoted to the study of the enzymatic degradation products of in vitro glycated human serum albumin (HSA). This approach, based on different MS methods (LC/ESI/MS, LC/ESI/FTMS, MALDI), led to the detection of the glycated peptides generated by digestion of HSA. A further study was devoted to the possible identification of the peptides identified in the glycated HSA digestion products in the plasma of diabetic and nephropatic subjects. No glycated HSA digestion products were found in plasma samples of the subjects under investigation even if clear differences were found among the LC runs from populations of healthy, diabetic, and nephropatic subjects. Parallel investigations were devoted to the evaluation of glyoxal and methylglyoxal-dicarbonyl compounds that originate at the intermediate stage of the Maillard reaction. This evaluation was performed in diabetic patients, before and after the achievement of good metabolic control, and in nephropatic patients subjected to peritoneal dialysis (PD). In the latter case, results indicated that these dicarbonyl compounds, already present in the dialysis fluids, show a decrease in plasma and in dialysis fluids; those data suggested their reaction at peritoneal membrane level.
本文综述了近期关于非酶蛋白糖基化的研究，并对研究结果进行了批判性讨论。体内晚期糖基化终产物（AGE）水平反映了其生成与分解代谢之间的平衡。AGE蛋白水解会导致形成通常经尿液排出的低分子量AGE（AGE肽）。在糖尿病和/或肾衰竭情况下，AGE肽会在血浆中蓄积。由于这些化合物具有高反应活性，人们认为它们在慢性并发症的进展中起作用。这些化合物的结构鉴定尤为重要，为此设计了一种策略来对其进行可能的定义。一系列实验致力于研究体外糖基化人血清白蛋白（HSA）的酶促降解产物。这种基于不同质谱方法（液相色谱/电喷雾电离/质谱、液相色谱/电喷雾电离/傅里叶变换质谱、基质辅助激光解吸电离）的方法，使得能够检测到HSA消化产生的糖基化肽。进一步的研究致力于在糖尿病和肾病患者血浆中鉴定糖基化HSA消化产物中所识别的肽。在所研究受试者的血浆样本中未发现糖基化HSA消化产物，即便在健康、糖尿病和肾病患者群体的液相色谱分析结果中发现了明显差异。同时开展的研究致力于评估源自美拉德反应中间阶段的乙二醛和甲基乙二醛二羰基化合物。在糖尿病患者实现良好代谢控制前后以及接受腹膜透析（PD）的肾病患者中进行了此项评估。在后一种情况下，结果表明这些已存在于透析液中的二羰基化合物在血浆和透析液中均有所减少；这些数据表明它们在腹膜水平发生了反应。
