Oxygen is not required for the browning and crosslinking of protein by pentoses: relevance to Maillard reactions in vivo

The chemical modification and crosslinking of proteins by the Maillard or browning reaction contributes to the aging of tissue proteins, and acceleration of this reaction during hyperglycemia is implicated in the pathogenesis of diabetic complications. Metal-catalyzed autoxidation reactions catalyze the browning of proteins by glucose, a process known as autoxidative glycosylation, but the effects of oxidative conditions on browning of proteins by smaller sugars has not been reported. In this work we studied the browning and crosslinking of the model protein, RNase A, by pentoses. Although antioxidative conditions inhibited the formation of glyoxal and the advanced glycation end-product, N epsilon-(carboxymethyl)lysine from arabinose, browning and crosslinking, and formation of the fluorescent crosslink pentosidine proceeded at comparable rates under oxidative and antioxidative conditions. These studies and other work on smaller dicarbonyl compounds indicate that Maillard reactions of simpler carbohydrates proceed efficiently in the absence of oxygen and suggest that antioxidant therapy for treatment of diabetic complications may have limited clinical efficacy.