Inhibition of glucokinase in hepatocytes by alloxan.
The effect of alloxan on glucokinase in isolated rat hepatocytes was studied. Exposure of hepatocytes to alloxan (3 mM) at 30 degrees C for 5 min produced a marked inhibition (77%) of glucokinase activity and altered slightly the phosphofructokinase activity (32% inhibition). Pyruvate kinase and glucose 6-phosphate dehydrogenase, however, were not inhibited at all. Alloxan induced a concentration-dependent inhibition of glucokinase activity with a detectable inhibition at an alloxan concentration of 1 mM. The inhibition of glucokinase activity by alloxan was protected by the simultaneous presence of 15 mM hexose such as D-glucose, 3-O-methylglucose, or D-mannose. D-Galactose showed no protective effect. These results suggest that alloxan may exert its cytotoxic action through the inhibition of glucokinase activity not only in the liver but also in the pancreatic islets, since liver and islet glucokinases are known to be quite similar in various properties.
D000496:Alloxan / Q000494:pharmacology*; D000818:Animals; D002374:Catalase / Q000378:metabolism; D004734:Energy Metabolism / Q000187:drug effects; D005941:Glucokinase / Q000037:antagonists & inhibitors*; D005954:Glucosephosphate Dehydrogenase / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D010732:Phosphofructokinase-1 / Q000378:metabolism; D011770:Pyruvate Kinase / Q000378:metabolism; D051381:Rats; D013482:Superoxide Dismutase / Q000378:metabolism
D000496:Alloxan; D005954:Glucosephosphate Dehydrogenase; D002374:Catalase; D013482:Superoxide Dismutase; D010732:Phosphofructokinase-1; D005941:Glucokinase; D011770:Pyruvate Kinase