Accumulation of glutamic acid in isolated brain tissue

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Abstract
Slices of guinea pig brain cortex, when suspended aero-bically in a saline medium containing glucose and L-glutamate, accumulate L-glutamate within the tissue. The transport of glutamate into the tissue occurs against a concn. gradient. Conditions for studying this phenomenon have been elaborated. Transport of L-glutamate into the tissue stopped when the difference between the concns. in the tissue and in the medium was about 0.02 [image]. The concn. of L-glutamate in the tissue fell when glucose was omitted from the medium. Substrates which supported accumulation of glutamate were glucose, fructose, L-lactate and pyruvate, but in most expts. glucose was more effective than the other substrates. Succinate, alpha-glycero-phosphate or excess of glutamate did not prevent the fall of the initial glutamate concn. in the brain, although these substances are readily oxidized by this tissue. While brain slices retained and accumulated L-glutamate, the very much larger molecules of the glutamic-aspartic transaminase readily diffused from the slices into the medium. L-Glutamine was taken up by brain tissue a little more rapidly than L-glutamate, but the final concns. reached were about the same. Anaerobically no appreciable accumulation occurred, but glucose delayed the fall of the initial concn. of glutamate in the tissue. D-Glutamate was converted into L-glutamate by brain slices. Adenosine-triphosphate abolished the inhibition of brain glycolysis by glutamate. It is suggested that the glutamate inhibition is due to an interaction between glutamate and adenosinetriphosphos-phate to form glutamyl-gamma-phosphate and that the removal of adenosinetriphosphate by this reaction is responsible for the slowing down of glycolysis.