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

Baldensperger, Tim, Jost, Tobias, Zipprich, Alexander, Glomb, Marcus A.
Journal of agricultural and food chemistry 2018 v.66 no.8 pp. 1898-1906
acids, liver, liver cirrhosis, lysine, models, oxidation, oxidative stress, rats, reference standards, tissues
The highly reactive α-dicarbonyl compounds glyoxal and methylglyoxal are major precursors of posttranslational protein modifications in vivo. Model incubations of N²-t-Boc-lysine and either glyoxal or methylglyoxal were used to further elucidate the underlying mechanisms of the N⁶-carboxymethyl lysine and N⁶-carboxyethyl lysine reaction cascades. After independent synthesis of the authentic reference standards, we were able to detect N⁶-glyoxylyl lysine and N⁶-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 N⁶-glyoxylyl lysine and N⁶-pyruvoyl lysine in rat livers indeed correlated with liver cirrhosis and aging.