Studies on the Maillard reaction: Mechanism of the fructosamine assay, decomposition of Amadori adducts on protein, and reaction of 3-deoxyglucosone with arginine residues in protein

The Maillard or browning reaction between reducing sugars and proteins contributes to the chemical aging of tissue proteins in vivo and to the accelerated aging of proteins in diabetes. The Amadori compound is the first stable adduct formed on glycation of proteins during the Maillard reaction and its concentration on blood proteins varies with mean blood glucose concentration. The fructosamine assay is a colorimetric test that is used clinically to measure Amadori adducts on serum protein. We have demonstrated that oxygen is not required in the fructosamine assay and that the products formed during the assay are the free amino acid and a dicarbonyl sugar, glucosone. We have also determined that Amadori adducts on protein undergo spontaneous decomposition under physiological conditions to more reactive sugars such as tetroses, pentoses and 3-deoxyglucosone. This provides a mechanism for generating reactive intermediates and for propagating damage to protein as a result of glycation of proteins by glucose in vivo. We also showed that 3-deoxyglucosone, a decomposition product of Amadori compounds, is a highly reactive sugar which reacts preferentially with the guanidino group of arginine residues in protein to form acid-stable imidazolone derivatives. Although these derivatives were not detected in vivo, they might be intermediates in the Maillard reaction, which proceed to form advanced glycation end-products.