Glycation reactions of methylglyoxal during digestion in a dynamic, in vitro model of the upper gastrointestinal tract (TIM-1)

The 1,2-dicarbonyl compound methylglyoxal (MGO) can react with and thereby impair the function of proteins and DNA, leading to pathophysiological pathways in vivo. However, studies on the bioavailability of dietary MGO and its reactions during digestion have diverging results. Therefore, simulated digestion experiments of MGO, protein, and creatine were performed in the dynamic, in vitro model of the upper gastrointestinal tract (TIM-1). This multicompartment model continuously adjusts pH values and has realistic gastrointestinal transit times while also removing water and metabolites by dialysis. Samples were analyzed with HPLC-UV for MGO and HPLC-MS/MS for creatine and glycated amino compounds. MGO reacted with creatine during simulated digestion in TIM-1 to form the hydroimidazolone MG-HCr in similar amounts as in a human intervention study. 28%-69% of MGO from the meal were passively absorbed in TIM-1, depending on the addition of creatine and protein. Simultaneous digestion of MGO with ovalbumin led to the formation of the lysine adduct N-epsilon-carboxyethyllysine (CEL) and the methylglyoxal-derived hydroimidazolone of arginine (MG-H1). The formation of both compounds decreased with added creatine. Hence, glycation compounds are formed during digestion and significantly contribute to other ingested dietary glycation compounds, whose physiological consequences are critically discussed.