Mechanism of the degradation of non-enzymatically glycated proteins under physiological conditions. Studies with the model fructosamine, N epsilon-(1-deoxy-D-fructos-1-yl)hippuryl-lysine.

The degradation of fructosamines, formed from the non-enzymic glycation of proteins under physiological conditions, to advanced glycation end products was investigated by studying the model peptide fructosamine N epsilon-(1-deoxy-D-fructos-1-yl)hippuryl-lysine (DHL). At pH 7.4 and 37 degrees C in aerobic phosphate buffer, DHL degraded to form N epsilon-carboxymethyl-hippuryl-lysine, and hippuryl-lysine over a 29-day incubation period. The expected N epsilon-(3-lactato)hippuryl-lysine and 'hippuryl-lysylpyrraline' derivatives were not found. Superoxide radicals and hydrogen peroxide were formed during the degradation of DHL but were also both consumed during the degradation reaction. Reversal of the Amadori rearrangement was not a major fate of the fructosamine. The formation of N epsilon-carboxymethyl-hippuryl-lysine was decreased by desferrioxamine, catalase, superoxide dismutase, catalase with superoxide dismutase, anaerobic conditions and aminoguanidine. The formation of hippuryl-lysine was decreased by desferrioxamine, catalase and catalase with superoxide dismutase, but was increased by the addition of aminoguanidine. N epsilon-Carboxymethyl-serine and unmodified lysine residues are major peptide-based end products in the degradation of lysyl-fructosamine under physiological conditions. Oxygen, redox-active metal ions, catalase, superoxide dismutase and the pharmacological agent aminoguanidine are expected to be influential on the rate and fate of fructosamine degradation.