N-EPSILON-(CARBOXYETHYL)LYSINE, A PRODUCT OF THE CHEMICAL MODIFICATION OF PROTEINS BY METHYLGLYOXAL, INCREASES WITH AGE IN HUMAN LENS PROTEINS

Advanced glycation end-products and glycoxidation products, such as N- epsilon-(carboxymethyl)lysine (CML) and pentosidine, accumulate in lon g-lived tissue proteins with age and are implicated in the aging of ti ssue proteins and in the development of pathology in diabetes, atheros clerosis and other diseases. In this paper we describe a new advanced glycation end-product, N-epsilon(carboxyethyl)lysine (CEL), which is f ormed during the reaction of methylglyoxal with lysine residues in mod el compounds and in the proteins RNase and collagen. CEL was also dete cted in human lens proteins at a concentration similar to that of CML, and increased with age in parallel with the concentration of CML. Alt hough CEL was formed in highest yields during the reaction of methylgl yoxal and triose phosphates with lysine and protein, it was also forme d in reactions of pentoses, ascorbate and other sugars with lysine and RNase. We propose that levels of CML and CEL and their ratio to one a nother in tissue proteins and in urine will provide an index of glyoxa l and methylglyoxal concentrations in tissues, alterations in glutathi one homoeostasis and dicarbonyl metabolism in disease, and sources of advanced glycation end-products in tissue proteins in aging and diseas e.