Protein Glycation

A bstract : In a glycation reaction, α‐dicarbonyl compounds such as deoxyglucosone, methylglyoxal, and glyoxal are more reactive than the parent sugars with respect to their ability to react with amino groups of proteins to form inter‐ and intramolecular cross‐links of proteins, stable end products called advanced Maillard products or advanced end products (AGEs). The AGEs, which are irreversibly formed, accumulate with aging, atherosclerosis, and diabetes mellitus, and are especially associated with long‐lived proteins such as collagens, lens crystallins, and nerve proteins. It was suggested that the formation of AGEs not only modifies protein properites but also induces biological damage in vivo . In this report, we summerize results obtained from our studies for (1) identifying the structure of the cross‐linked radical species formed in the model system—the reaction between α‐dicarbonyl methylglyoxal with amino acids, and (2) the reactivity of the radical center of the protein created by the similar reaction. These results indicate that glycation of protein generates active centers for catalyzing one‐electron oxidation‐reduction reactions. This active center, which exhibits enzyme‐like character, is suggested to be the cross‐linked Schiff‐based radical cation of the protein. It mimics the characteristics of the metal‐catalyzed oxidation system. These results together indicate that glycated proteins accumulated in vivo provide stable active sites for catalyzing the formation of free redicals.