METABOLIC COMPARTMENTATION IN THE BRAIN: EFFECTS OF A CENTRAL NERVOUS SYSTEM DEPRESSANT, 1‐HYDROXY‐3‐AMINO‐PYRROLIDONE‐2

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Abstract
—The effect of 1‐hydroxy‐3‐aminopyrrolidone‐2(HA‐966), a CNS depressant, was studied on the metabolism of [14C]glucose and [3H]acetate in the brain in mice. HA‐966 had a marked effect on glucose metabolism. The conversion of glucose carbon into amino acids associated with the tricarboxylic acid cycle (‘cycle’) was severely reduced, while the concentration of brain glucose was approximately doubled. Relative to the specific radioactivity of glucose in the brain, the specific radioactivity of alanine was 60–70 per cent of the control, indicating a reduction in the rate of glycolysis, and those of the‘cycle’amino acids were also lowered. A reduction in‘cycle’flux of 30–35 per cent was estimated. It was established that the depressed glucose utilization flux was not due to either impaired uptake of glucose from blood to brain or to hypothermia. In contrast to [14C]glucose, there was no change in the labelling of the amino acid fraction from [3H]acetate, which is preferentially metabolized in the 'small’compartment believed to be associated with glia. Thus it seems that CNS depression caused by HA‐966 resulted in a selective decrease in energy production in the‘large’metabolic compartment where glucose is oxidized preferentially and which is believed to be associated with neuronal structures.The results also suggested that communication between the metabolic compartments mediated via glutamine and GABA was reduced, since the labelling from [3H]acetate of glutamine was increased and that of GABA decreased by HA‐966.