Key enzymes of glycolysis in brain as influenced by thiopental.
It has been demonstrated in previous work that hexokinase is solubilized from the mitochondrial membrane in anesthesia. In the present investigation this effect was strongly correlated with the surgical stage of anesthesia by the application of thiopental to rats (80 mg/kg), mice (100 mg/kg) and guinea pigs (32 mg/kg). The solubilization of hexokinase was demonstrable, too, in different areas of rat brains under thiopental treatment (80 mg/kg). In order to elevate the cerebral concentration of glucose 6-phosphate, which is the most potent substrate for the solubilization of bound hexokinase, male Sprague-Dawley rats were pretreated with the antimetabolite 6-aminonicotinamide (6-AN). After i.p. injection of 6-AN (35 mg/kg) we measured an increased activity of soluble brain hexokinase in the same order of magnitude as it was determined in anesthesia. Thiopental application did not show a further significant increase. A solubilization of hexokinase activity by 6-AN was not measurable in vitro. Furthermore, we examined the other key enzymes in the glycolytic pathway. We found a competitive inhibition of phosphofrucktokinase activity by thiopental, but no inhibition of hexokinase and pyruvate-kinase activity.
D000758:Anesthesia; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000201:enzymology* / Q000648:ultrastructure; D006019:Glycolysis / Q000187:drug effects*; D006168:Guinea Pigs; D006593:Hexokinase / Q000378:metabolism; D007700:Kinetics; D008297:Male; D051379:Mice; D008928:Mitochondria / Q000201:enzymology; D010732:Phosphofructokinase-1 / Q000378:metabolism; D011770:Pyruvate Kinase / Q000378:metabolism; D051381:Rats; D013874:Thiopental / Q000494:pharmacology*
D006593:Hexokinase; D010732:Phosphofructokinase-1; D011770:Pyruvate Kinase; D013874:Thiopental