CHEMICAL MODIFICATION OF PROTEINS BY METHYLGLYOXAL

Methylglyoxal is formed in vivo by spontaneous decomposition of triose phosphate intermediates in aerobic glycolysis. It may also be formed during oxidative degradation of both carbohydrates (pentoses and ascor bate) and lipids (arachidonate). In addition to reaction with arginine residues to form imidazolone adducts, methylglyoxal reacts with lysin e residues in protein to form N-epsilon-(carboxyethyl)lysine (CEL) and the imidazolium crosslink, methylglyoxal-lysine dimer (MOLD). Like th e glycoxidation products, N-epsilon-(carboxymethyl)lysine (CML) and gl yoxal-lysine dimer (GOLD) which are formed on reaction of glyoxal with protein, CEL and MOLD increase in lens proteins and skin collagen wit h age. CML and CEL also increase in skin collagen in diabetes, while a ll four compounds increase in plasma proteins in uremia. Overall, CML, GEL, GOLD and MOLD are quantitatively the major biomarkers of the Mai llard reaction in tissue proteins. GOLD and MOLD, in particular, are p resent at 10-50 fold higher concentrations than the fluorescent crossl ink, pentosidine. Together, these dicarbonyl-derived advanced glycatio n endproducts (AGEs) represent the major chemical modifications that a ccumulate in tissue proteins with age and in chronic diseases such as diabetes and atherosclerosis.