Abstract：
Post-translational modification of proteins by Maillard reaction, known as glycation, is thought to be the root cause of different complications, particularly in diabetes mellitus and age-related disorders. Methylglyoxal (MG), a reactive α-oxoaldehyde, increases in diabetic condition and reacts with the proteins to form advanced glycation end products (AGEs) following a Maillard-like reaction. In a time-dependent reaction study of MG with the heme protein myoglobin (Mb), MG was found to induce significant structural alterations of the heme protein, such as heme loss, changes in tryptophan fluorescence, and decrease of α-helicity with increased β-sheet content. These changes were found to occur gradually with increasing period of incubation. Incubation of Mb with MG induced the formation of several AGE adducts, including, carboxyethyllysine at Lys-16, carboxymethyllysine at Lys-87, carboxyethyllysine or pyrraline-carboxymethyllysine at Lys-133, carboxyethyllysine at Lys-42 and hydroimidazolone or argpyrimidine at Arg-31 and Arg-139. MG induced amyloid-like aggregation of Mb was detected at a longer period of incubation. MG-derived AGEs, therefore, appear to have an important role as the precursors of protein aggregation, which, in turn, may be associated with pathophysiological complications.
摘要：
通过美拉德反应对蛋白质进行翻译后修饰，被称为糖化，被认为是不同并发症的根本原因，特别是糖尿病和年龄相关疾病。甲基乙二醛（MG），一种反应性α-氧代醛,在美拉德样反应后,糖尿病状况增加并与蛋白质反应形成晚期糖基化终产物(AGEs)。在MG与血红素蛋白肌红蛋白（Mb）的时间依赖性反应研究中，发现MG可诱导血红素蛋白的显着结构改变，如血红素损失，色氨酸荧光的变化，随着β-折叠含量的增加，α-螺旋度降低。发现这些变化随着潜伏期的增加而逐渐发生。Mb与MG的孵育诱导了几种AGE加合物的形成，包括,Lys-16处的羧乙基赖氨酸，Lys-87处的羧甲基赖氨酸，Lys-133处的羧乙基赖氨酸或吡啶-羧甲基赖氨酸，Lys-42处的羧乙基赖氨酸和Arg-31和Arg-139处的氢咪唑酮或嘧啶。在更长的孵育时间内检测到MG诱导的Mb的淀粉样蛋白样聚集。MG衍生的AGEs，因此,作为蛋白质聚集的前体似乎具有重要作用，which,反过来,可能与病理生理并发症有关。
