Non-Enzymatic Glycosylation and Deglycating Enzymes

Biological amines react with reducing sugars to form a heterogeneous group of compounds, called advanced glycation end products, a process known as the Maillard reaction. Glycation of proteins starts with formation of Shiff's base, which rearrange into Amadori product. The Amadori products then undergo a series of chemical modifications to form advanced glycation end products (AGEs). Many advanced glycation end products are capable of forming cross-links between proteins and many of them are fluorophores. The formation of AGEs is an irreversible process and glycation is a major cause of spontaneous damage to proteins in physiological systems. AGEs accumulate in tissues with age and their rate of accumulation is accelerated in diabetes. Hyperglycemia in diabetes causes accelerated AGEs formation and has been linked to various diabetic complications like nephropathy, retinopathy, angiopathy, and neuropathy.Nature has several defense mechanisms to protect tissues from AGEs accumulation. Among them are amadoriases, which can remove the Amadori product and interrupt the glycation cascade in the early steps of the Maillard reaction. To date three classes of deglycating enzymes were found-fructosamine oxidases, fructosamine-3-kinases, and fructoselysine 6-phosphate deglycase. These enzymes are known to occur in mammalian, fungal and other eukaryotic and prokaryotic cells.