Use of ¹³C Labeling and NMR Spectroscopy for the Investigation of Degradation Pathways of Amadori Compounds

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The degradation pathways of Amadori compounds in vivo have not been fully understood because of the lack of suitable techniques although the compounds are considered to be key intermediates in glycation, which contributes to the development of pathologies associated with various chronic and age-related diseases. A new approach using ¹³C labeling and NMR spectroscopy has thus been described to obtain more insight into the degradation pathways. A ¹³C-labeled model Amadori compound, [1-¹³C]N^ε-(1-deoxy-D-fructos-1-yl)hippuryl-lysine, was synthesized to investigate the degradation pathways of the sugar moiety. The labeled compound was then incubated under aerobic and physiologic conditions, followed by analysis using ¹³C-NMR spectroscopy to obtain the degradation profile. Consequently, after 28-d incubation at least nine ¹³C signals due to ¹³C-labeled products were observed with those due to unlabeled hippuryl-lysine. These labeled products included not only carboxymethylated hippuryl-lysine as the major product and α- and β-glucose but also acetate and formate. These experiments demonstrate the potential of using a ¹³C label and NMR spectroscopy in that the technique provides the comprehensive profiling of the degradation products containing the labeled position in spite of their chemical structures.