Short-chained carbonyl compounds like glycolaldehyde and glyoxal are very potent precursors of posttranslational protein modifications. These Maillard intermediates trigger the formation of e.g. the N6-carboxymethyllysine (CML) cascade, which includes CML, glycolic acid lysine amide (GALA), glyoxal lysine amide (GOLA) and glyoxal lysine dimer (GOLD). The reaction with arginine leads kinetically controlled to a dihydroxyimidazolidine, which hydrolyses to give the thermodynamically controlled endproduct N7-carboxymethyl arginine (CMA). The formation of glyoxal in vivo has been argued by increase in oxidative and carbonyl stress and thus been linked to various pathologies like uremia or diabetes. On the other hand, glycolaldehyde formation in vivo is so far only reported to stem from the degradation of the amino acid L-serine in presence of hypochlorous acid formed from superoxide and chloride by myeloperoxidase at sites of inflammation, but no concentrations are available. Here, we report for the first time on glycolaldehyde measured in vivo for healthy versus uremic human subjects. Second, to further explore alternative generation/detoxification pathways of this highly reactive Maillard agent we used model incubations with recombinant transketolase from E. coli in presence of bovine serum albumin and hydroxypyruvate and ribose-5-phosphate as the donor and acceptor substrates, respectively. No glycolaldehyde of the intermediate dihydroxyethyl thiamine diphosphate was released to the reaction mixture. In contrast, when glycolaldehyde was added to the incubation the carbonyl served as an alternative acceptor molecule to give erythrulose. In parallel the formation of glycolaldehyde mediated AGEs was significantly suppressed. This implies that transketolase activity in vivo might be crucial to control non-enzymatic glycolaldehyde Maillard reactivity.

Transketolase suppresses glycolaldehyde/glyoxal mediated formation of advanced glycation endproducts

254th National Meeting (2017)

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