Protein glycation

Spontaneous non-enzymatic reaction of protein amino groups with glucose and other reducing sugars is known as glycation. Glycation is a major cause of spontaneous damage to cellular and extracellular proteins in physiological systems. Though glucose is the major reducind sugar in body compartments, phosphorylated carbonyls produced by carbohydrate metabolism (eg. glucose-6-phosphate, ribose-5-phosphate and erythrulose-4-phosphate) are even more potent glycating agents. In addition to glucose and other reducing sugars, reactive carbonyls in the diet and those that are produced by lipid peroxidation can lead to glycation of proteins. The initial products of protein glycation, the ketoamines, are not stable and are slowly converted into large number of glycation end products via oxidative and non-oxidative mechanisms. Ketoamines including fructosamine on proteins are repaired in human by intracellular enzymes fructosamine-3-kinase and fructosamine-3-kinase related protein. Despite the presence of deglycating enzymes, advanced protein glycation is an inevitable process and accumulation of advanced glycation end products is exacerbated in diabetes as a consequence of the increase in glucose concentration. The accumulation of glycation end products is implicated in several disease states including the development of vascular, renal, retinal and neural complications of diabetes. Glycated proteins interact with their receptors and trigger pro-inflammatory gene activation. Activation of these receptors has a causative effect in a range of inflammatory diseases.