title: The reaction of methylglyoxal with aminoguanidine under physiological conditions and prevention of methylglyoxal binding to plasma proteins.
abstract: Increased formation of methylglyoxal in clinical diabetes mellitus and metabolism by the glyoxalase system has been linked to the development of clinical complications of diabetes: retinopathy, neuropathy and nephropathy. Aminoguanidine has been proposed as a prophylactic agent for preventive therapy of diabetic complications. Methylglyoxal reacted with aminoguanidine under physiological conditions to form two isomeric triazines, 3-amino-5-methyl-1,2,4-triazine and 3-amino-6-methyl-1,2,4-triazine. The mean second order rate constant for the reaction of methylglyoxal with aminoguanidine, kMG.AG = 0.39 +/- 0.06 M-1 sec-1 at pH 7.4 and 37 degrees. Under these conditions, no methylglyoxal bisguanylhydrazone was detected. Aminoguanidine prevented the irreversible modification of human plasma protein by a physiological concentration of methylglyoxal (1 microM); the median inhibitory concentration IC50 value of aminoguanidine was 203 +/- 16 microM (N = 28). The scavenging of methylglyoxal by aminoguanidine may contribute to the beneficial effects of aminoguanidine in the prevention of vascular pathogenesis in diabetes.
authors.affiliation: Department of Chemistry and Biological Chemistry, University of Essex, Colchester, U.K.
authors.forename: T W
authors.initials: TW
authors.lastname: Lo
authors.forename: T
authors.initials: T
authors.lastname: Selwood
authors.forename: P J
authors.initials: PJ
authors.lastname: Thornalley
mesh_terms: D001798:Blood Proteins / Q000378:metabolism*; D006146:Guanidines / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D011485:Protein Binding; D011765:Pyruvaldehyde / Q000378:metabolism*
chemical_list: D001798:Blood Proteins; D006146:Guanidines; D011765:Pyruvaldehyde; C004479:pimagedine