IMIDAZOLIUM CROSS-LINKS DERIVED FROM REACTION OF LYSINE WITH GLYOXAL AND METHYLGLYOXAL ARE INCREASED IN SERUM-PROTEINS OF UREMIC PATIENTS -EVIDENCE FOR INCREASED OXIDATIVE STRESS IN UREMIA

Glyoxal (GO) and methylglyoxal (MGO) are reactive dicarbonyl compounds formed during autoxidation of both carbohydrates and lipids. They may react with lysine and arginine residues of proteins in Maillard or br owning reactions, yielding advanced glycation or lipoxidation end prod ucts, Among these are the imidazolium crosslinks, N,N(-di(N-epsilon-ly sino))imidazolium (glyoxal-lysine dimer, GOLD) and N,N(-di(N-lysino))4 -methyl-imidazolium (methylglyoxal-lysine dimer, MOLD). We have detect ed and measured GOLD and MOLD in human serum by electrospray ionizatio n/mass spectrometry/mass spectrometry (ESI/MS/MS), using N-15(4)-GOLD and N-15(4)-MOLD as internal standards. In this report we show that le vels of GOLD and MOLD are significantly elevated (3-4-fold, P < 0.01) in sera of non-diabetic uremic patients, compared to age-matched contr ols, and represent a major class of non-enzymatic, Maillard reaction c rosslinks in plasma proteins. These results provide strong evidence fo r increased non-enzymatic crosslinking of tissue proteins by GO and MG O in uremia, implicating oxidative stress and resultant advanced glyca tion and lipoxidation reactions in tissue damage in uremia. (C) 1998 F ederation of European Biochemical Societies.