Sequential alterations of cerebral carbohydrate metabolism associated with gamma-hydroxybutyrate.
The cerebral metabolic effects of intravenous administration of 1000 mg/kg gamma-hydroxybutyrate (GHB) were studied by sequential measurement of the cerebral contents of selected glycolytic-citric acid cycle intermediates and energy phosphates in lightly anesthetized rats. The initial change in the glycolytic pathway occurred by 2.5 min, with increases of tissue glucose-6-phosphate and decreases of fructose-1,6- diphosphate which indicated an inhibition of phosphofructokinase. This pattern was transient and was replaced at 5--15 min by increasing tissue glucose and decreasing glucose-6-phosphate which indicated an inhibition of hexokinase. The initial inhibition of phosphofructokinase was associated with functional depression, an isoelectric EEG and an increase of the tissue phosphocreatine which suggested that the observed metabolic pattern was an adaptation to the reduced energy needs of neuronal depression. Within 2.5 min of GHB injection tissue alpha-ketoglutarate and aspartate showed significant increases which suggested a shift in the aspartate aminotransferase reaction. Preliminary calculations indicated that the probable cause of this shift was an increase in oxaloacetate content due to GHB oxidation. The cytoplasmic NADH/NAD+ ratio remained unchanged throughout the entire exposure to GHB (2.5--180 min) and thus gave no support for the hypothesis that GHB interfers with glycolysis via the restriction of free cytoplasmic NAD+ required for the glyceraldehyde phosphate dehydrogenase step.
D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D050260:Carbohydrate Metabolism; D002540:Cerebral Cortex / Q000187:drug effects* / Q000201:enzymology; D002952:Citric Acid Cycle / Q000187:drug effects; D004569:Electroencephalography; D005071:Evoked Potentials / Q000187:drug effects; D005635:Fructosediphosphates / Q000378:metabolism; D005958:Glucosephosphates / Q000378:metabolism; D006003:Glycogen / Q000378:metabolism; D006885:Hydroxybutyrates / Q000494:pharmacology*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D009243:NAD / Q000378:metabolism; D051381:Rats
D000596:Amino Acids; D001786:Blood Glucose; D005635:Fructosediphosphates; D005958:Glucosephosphates; D006885:Hydroxybutyrates; D009243:NAD; D006003:Glycogen; D007770:L-Lactate Dehydrogenase