Modification of the glyoxalase system in human red blood cells by glucose in vitro.
The human red-blood-cell glyoxalase system was modified by incubation with high concentrations of glucose in vitro. Red-blood-cell suspensions (50%, v/v) were incubated with 5 mM- and 25 mM-glucose to model normal and hyperglycaemic glucose metabolism. There was an increase in the flux of methylglyoxal metabolized to D-lactic acid via the glyoxalase pathway with high glucose concentration. The increase was approximately proportional to initial glucose concentration over the range studied (5-100 mM). The activities of glyoxalase I and glyoxalase II were not significantly changed, but the concentrations of the glyoxalase substrates, methylglyoxal and S-D-lactoylglutathione, and the percentage of glucotriose metabolized via the glyoxalase pathway, were significantly increased. The increase in the flux of intermediates metabolized via the glyoxalase pathway during periodic hyperglycaemia may be a biochemical factor involved in the development of chronic clinical complications associated with diabetes mellitus.
Thornalley
P J
PJ
MRC Mechanisms of Drug Toxicity Group, Aston University, Birmingham, U.K.
D004912:Erythrocytes / Q000187:drug effects / Q000201:enzymology*; D005947:Glucose / Q000494:pharmacology*; D005978:Glutathione / Q000031:analogs & derivatives / Q000097:blood; D006801:Humans; D006943:Hyperglycemia / Q000097:blood / Q000201:enzymology; D066298:In Vitro Techniques; D007773:Lactates / Q000097:blood; D019344:Lactic Acid; D007791:Lactoylglutathione Lyase / Q000097:blood*; D008190:Lyases / Q000097:blood*; D008954:Models, Biological; D011765:Pyruvaldehyde / Q000097:blood; D014312:Trisaccharides / Q000097:blood*
D007773:Lactates; D014312:Trisaccharides; D019344:Lactic Acid; D011765:Pyruvaldehyde; D008190:Lyases; D007791:Lactoylglutathione Lyase; D005978:Glutathione; D005947:Glucose; C013585:S-lactoylglutathione