Novel α-Oxoamide Advanced-Glycation Endproducts within the N6-Carboxymethyl Lysine and N6-Carboxyethyl Lysine Reaction Cascades

被引:28
作者
Baldensperger, Tim [1 ]
Jost, Tobias [1 ]
Zipprich, Alexander [2 ]
Glomb, Marcus A. [1 ]
机构
[1] Martin Luther Univ Halle Wittenberg, Inst Chem, Food Chem, Kurt Mothes Str 2, D-06120 Halle, Germany
[2] Martin Luther Univ Halle Wittenberg, Dept Internal Med 1, Ernst Grube Str 40, D-06120 Halle, Germany
关键词
Maillard reaction; amide advanced-glycation endproducts; methylglyoxal; glyoxal; oxidative stress; aging; MAILLARD REACTION; IN-VIVO; PROTEIN MODIFICATIONS; DICARBONYL COMPOUNDS; DEGRADATION; PATHWAYS; ACIDS; FRAGMENTATION; METHYLGLYOXAL; HISTORY;
D O I
10.1021/acs.jafc.7b05813
中图分类号
S [农业科学];
学科分类号
09 ;
摘要
The highly reactive alpha-dicarbonyl compounds glyoxal and methylglyoxal are major precursors of posttranslational protein modifications in vivo. Model incubations of N-2-t-Boc-lysine and either glyoxal or methylglyoxal were used to further elucidate the underlying mechanisms of the N-6-carboxymethyl lysine and N-6-carboxyethyl lysine reaction cascades. After independent synthesis of the authentic reference standards, we were able to detect N-6-glyoxylyl lysine and N-6-pyruvoyl lysine for the first time by HPLC-MS2 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-6-glyoxylyl lysine and N-6-pyruvoyl lysine in rat livers indeed correlated with liver cirrhosis and aging.
引用
收藏
页码:1898 / 1906
页数:9
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