Title: Formation of pentosidine during nonenzymatic browning of proteins by glucose. Identification of glucose and other carbohydrates as possible precursors of pentosidine in vivo
Abstract: A fluorescent compound has been detected in proteins browned during Maillard reactions with glucose in vitro and shown to be identical to pentosidine, a pentose-derived fluorescent cross-link formed between arginine and lysine residues in collagen (Sell, D. R., and Monnier, V. M. (1989) J. Biol.Chem.264, 21597-2 1602).Pentosidine was the major fluorophore formed during nonenzymatic browning of ribonuclease and lysozyme by glucose, but accounted for <1% of nondisulfide cross-links in protein dimers formed during the reaction.Pentosidine was formed in greatest yields in reactions of pentoses with lysine and arginine in model systems but was also formed from glucose, fructose, ascorbate, Amadori compounds, 3-deoxyglucosone, and other sugars.Pentosidine was not formed from peroxidized polyunsaturated fatty acids or malondialdehyde.Its formation from carbohydrates was inhibited under nitrogen or anaerobic conditions and by aminoguanidine, an inhibitor of advanced glycation and browning reactions.Pentosidine was detected in human lens proteins, where its concentration increased gradually with age, but it did not exceed trace concentrations (55 Fmol/mol lysine), even in the 80-year-old lens.Although its precise carbohydrate source in vivo is uncertain and it is present in only trace concentrations in tissue proteins, pentosidine appears to be a useful biomarker for assessing cumulative damage to proteins by nonenzymatic browning reactions with carbohydrates.Glycation (nonenzymatic glycosylation) and Maillard (nonenzymatic browning) reactions of proteins by reducing sugars are thought to contribute to the aging and cross-linking of tissue proteins (1-3).Acceleration of these reactions as a result of hyperglycemia in diabetes and the consequent increase in structural and functional modification of long-lived proteins are implicated in the pathogenesis of the chronic complications of diabetes (4).Since the extent of glycation of protein is relatively constant with age (5-7), a major challenge in research on the Maillard reaction in vivo is to identify specific products formed in tissue proteins during later stages