title: Modulation of plasminogen activation and plasmin activity by methylglyoxal modification of the zymogen.
abstract: The effect of methylglyoxal on the plasminogen-plasmin system is studied. Treatment of plasminogen with methylglyoxal at a 20-fold molar excess results in covalent modification of the molecule as evidenced by the decreased number of NH(2) side chains, arginine side chain residues and the new band in the non-tryptophan dependent fluorescent spectrum. This structural modification is associated with profound functional alterations: the rate of activation by streptokinase, tissue-type plasminogen activator, urokinase-type plasminogen activator and trypsin decreases and the amidolytic activity of the generated plasmin is impaired. Plasmin treatment with methylglyoxal on the other hand does not alter its steady-state kinetic parameters on a peptidyl-anilide synthetic substrate, indicating that modification susceptible side chains are sensitive to methylglyoxal only in the zymogen. Our data suggest that in vivo fibrinolysis could be impaired under pathological conditions, e.g. increased methylglyoxal formation in diabetes mellitus.
authors.affiliation: Department of Medical Biochemistry at Semmelweis University, Budapest, Hungary.
authors.forename: I
authors.initials: I
authors.lastname: Léránt
authors.forename: K
authors.initials: K
authors.lastname: Kolev
authors.forename: J
authors.initials: J
authors.lastname: Gombás
authors.forename: R
authors.initials: R
authors.lastname: Machovich
mesh_terms: D000818:Animals; D001120:Arginine / Q000737:chemistry; D002384:Catalysis; D004591:Electrophoresis, Polyacrylamide Gel; D005341:Fibrinolysin / Q000737:chemistry / Q000378:metabolism*; D005342:Fibrinolysis; D007700:Kinetics; D008239:Lysine / Q000737:chemistry; D008297:Male; D010958:Plasminogen / Q000737:chemistry / Q000378:metabolism*; D011765:Pyruvaldehyde / Q000737:chemistry*; D051381:Rats; D017208:Rats, Wistar; D013050:Spectrometry, Fluorescence
chemical_list: D011765:Pyruvaldehyde; D010958:Plasminogen; D001120:Arginine; D005341:Fibrinolysin; D008239:Lysine