Monosaccharide autoxidation: A potential source of oxidative stress in diabetes?. Model reactions with nucleotides and protein

Monosaccharide autoxidation (the metal-catalysed oxidation of monosaccharide enediol yielding ketoaldehydes, hydrogen peroxide and free radical intermediates) may contribute to hyperglycaemia-associated tissue oxidation. Oxidation reactions associated with monosaccharides were studies using model reactions with NADPH and protein. Glyceraldehyde stimulated the biphasic oxidation of NADPH. The reaction was hydrogen peroxide-dependent and was rapid after attainment of anaerobiosis, suggesting the involvement of carbon-centred radicals. Oxygen thus appeared to act both as pro- and anti-oxidant. Monosaccharide autoxidation was found to contribute to protein glycosylation. Incorporation of glucose into protein was inhibited by diethylenetriaminepentaacetic acid (DETAPAC), which sequesters trace amounts of transition metals and inhibits glucose autoxidation. Glucose-derived ketoaldehydes also appear to contribute to browning reactions. DETAPAC inhibited protein chromo- and fluorophoric alterations associated with glycosylation. Ketoaldehyde-BSA adduct autoxidation, generating superoxide, may be a further source of oxidative stress associated with monosaccharides. Monosaccharides autoxidation is a candidate for the increased oxidative stress evident in diabetes.