<i>N</i> ε-(Carboxyethyl)lysine, a product of the chemical modification of proteins by methylglyoxal, increases with age in human lens proteins

TLDR

Advanced glycation end‑products such as CML and pentosidine accumulate in long‑lived proteins with age and contribute to tissue aging and diseases like diabetes and atherosclerosis. The study introduces the novel AGE Nϵ‑carboxyethyllysine (CEL) and proposes that its tissue and urinary levels, together with CML, can serve as an index of glyoxal/methylglyoxal exposure, glutathione homeostasis, and dicarbonyl metabolism in aging and disease. CEL forms when methylglyoxal reacts with lysine residues in proteins, and can also arise from reactions of pentoses, ascorbate, and other sugars with lysine. CEL was detected in human lens proteins at concentrations similar to CML and increased with age in parallel with CML levels.

Abstract

Advanced glycation end-products and glycoxidation products, such as Nϵ-(carboxymethyl)lysine (CML) and pentosidine, accumulate in long-lived tissue proteins with age and are implicated in the aging of tissue proteins and in the development of pathology in diabetes, atherosclerosis and other diseases. In this paper we describe a new advanced glycation end-product, Nϵ-(carboxyethyl)lysine (CEL), which is formed during the reaction of methylglyoxal with lysine residues in model compounds and in the proteins RNase and collagen. CEL was also detected in human lens proteins at a concentration similar to that of CML, and increased with age in parallel with the concentration of CML. Although CEL was formed in highest yields during the reaction of methylglyoxal and triose phosphates with lysine and protein, it was also formed 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 another in tissue proteins and in urine will provide an index of glyoxal and methylglyoxal concentrations in tissues, alterations in glutathione homoeostasis and dicarbonyl metabolism in disease, and sources of advanced glycation end-products in tissue proteins in aging and disease.