Inhibition of the glycolytic pathway by methylglyoxal in human platelets.
The incubation of human platelets with methylglyoxal and glucose produces a rapid transformation of the ketoaldehyde to D-lactate by the glyoxalase system and a partial reduction in GSH. Glucose utilization is affected at the level of the glycolytic pathway. No effect of the ketoaldehyde on glycogenolysis and glucose oxidation through the hexose monophosphate shunt was demonstrated. Phosphofructokinase, fructose 1,6 diphosphate (F1, 6DP) aldolase, glyceraldehyde 3-phosphate dehydrogenase and 3-phosphoglycerate mutase were mostly inhibited by methylglyoxal. A decrease in lactate and pyruvate formation and an accumulation of some glycolytic intermediates (fructose 1,6 diphosphate, dihydroxyacetone phosphate, 3-phosphoglycerate) was observed. Moreover methylglyoxal induced a fall in the metabolic ATP concentration. Since methylglyoxal is an intermediate of the glycolytic bypass system from dihydroxyacetone phosphate to D-lactate, it may be assumed that ketoaldehyde exerts a regulating effect on triose metabolism.
Leoncini
G
G
Istituto Policattedra di Chimica Biologica, Università di Genova, Italy.
Maresca
M
M
Buzzi
E
E
D000227:Adenine Nucleotides / Q000097:blood; D000447:Aldehydes / Q000494:pharmacology*; D001786:Blood Glucose / Q000378:metabolism; D001792:Blood Platelets / Q000378:metabolism*; D004734:Energy Metabolism / Q000187:drug effects; D006019:Glycolysis / Q000187:drug effects*; D006801:Humans; D007773:Lactates / Q000096:biosynthesis; D010084:Oxidation-Reduction / Q000187:drug effects; D011765:Pyruvaldehyde / Q000097:blood / Q000494:pharmacology*; D011773:Pyruvates / Q000096:biosynthesis; D013997:Time Factors
D000227:Adenine Nucleotides; D000447:Aldehydes; D001786:Blood Glucose; D007773:Lactates; D011773:Pyruvates; D011765:Pyruvaldehyde