Baldensperger Tim, Jost Tobias, Zipprich Alexander, Glomb Marcus A
Institute of Chemistry, Food Chemistry, Martin-Luther-University Halle-Wittenberg , Kurt-Mothes-Strasse 2, 06120 Halle/Saale, Germany.
Department of Internal Medicine I, Martin-Luther-University Halle-Wittenberg , Ernst-Grube-Strasse 40, 06120 Halle/Saale, Germany.
J Agric Food Chem. 2018 Feb 28;66(8):1898-1906. doi: 10.1021/acs.jafc.7b05813. Epub 2018 Feb 13.
The highly reactive α-dicarbonyl compounds glyoxal and methylglyoxal are major precursors of posttranslational protein modifications in vivo. Model incubations of N-t-Boc-lysine and either glyoxal or methylglyoxal were used to further elucidate the underlying mechanisms of the N-carboxymethyl lysine and N-carboxyethyl lysine reaction cascades. After independent synthesis of the authentic reference standards, we were able to detect N-glyoxylyl lysine and N-pyruvoyl lysine for the first time by HPLC-MS analyses. These two novel amide advanced-glycation endproducts were exclusively formed under aerated conditions, suggesting that they were potent markers for oxidative stress. Analogous to the well-known Strecker degradation pathway, leading from amino acids to Strecker acids, the oxidation of an enaminol intermediate is suggested to be the key mechanistic step. A highly sensitive workup for the determination of AGEs in tissues was developed. In support of our hypothesis, the levels of N-glyoxylyl lysine and N-pyruvoyl lysine in rat livers indeed correlated with liver cirrhosis and aging.
高反应性的α-二羰基化合物乙二醛和甲基乙二醛是体内蛋白质翻译后修饰的主要前体。使用N-叔丁氧羰基赖氨酸与乙二醛或甲基乙二醛进行模型孵育，以进一步阐明N-羧甲基赖氨酸和N-羧乙基赖氨酸反应级联的潜在机制。在独立合成真实参考标准品后，我们首次通过高效液相色谱-质谱分析检测到了N-乙二醛基赖氨酸和N-丙酮酰赖氨酸。这两种新型酰胺晚期糖基化终产物仅在通气条件下形成，表明它们是氧化应激的有效标志物。类似于从氨基酸到斯特雷克酸的著名斯特雷克降解途径，烯胺醇中间体的氧化被认为是关键的机制步骤。我们开发了一种用于测定组织中晚期糖基化终产物的高灵敏度检测方法。支持我们的假设的是，大鼠肝脏中N-乙二醛基赖氨酸和N-丙酮酰赖氨酸的水平确实与肝硬化和衰老相关。
