Abstract

Glycation is the non-enzymatic glycosylation of proteins, nucleotides and lipids by saccharide derivatives. It is now thought to contribute to the development of chronic vascular complications of diabetes, non-diabetic nephropathy, macrovascular disease, Alzheimer's disease and aging. Glycation of proteins leads to covalent crosslinking and abnormal structural stabilization of extracellular matrix proteins, and recognition by specific receptors "AGE receptors" and consequent cell activation. Glycation of nucleotides contributes to endogenous mutagenesis. Glycation of lipids may initiate lipid peroxidation and contribute to lipid turnover. Glucose and other saccharides are important glycating agents but the most reactive glycating agents are the α-oxoaldehydes, glyoxal, methylglyoxal and 3-deoxyglucosone. Early glycation adducts (Schiff's base, fructosamine) and advanced glycation adducts (AGEs) are formed. Glycation is an unavoidable, minor feature of physiological metabolism. In certain pathophysiological states, one or more of the follow changes to glycation-related processes occurs: the rate of glycation is increased, the renal clearance of AGEs is decreased and/or the expression of AGE receptors is increased. This may lead to AGE-related basement membrane thickening, AGE-mediated cell activation and amyloidosis. Fructosamines are indicators of medium term glycaemic control and AGEs indicators of medium to long term glycaemic control in diabetes mellitus. Some AGEs are risk markers and some may be risk factors of disease. The future challenges are to identify critical AGEs and AGE receptors involved in protein crosslinking and cell activation, to characterize their participation in disease mechanisms, and to develop safe and effective therapeutic agents to counter glycation-mediated pathogenesis.

DOI: CIin. Lab. 1999;45:263-273