THE INHIBITION IN VIVO OF CEREBRAL GLUTAMINE SYNTHETASE AND GLUTAMINE TRANSFERASE BY THE CONVULSANT METHIONINE SULFOXIMINE.

Abstract Evidence is presented for an in vivo interaction of the convulsant agent methionine sulfoximine (MSO) with glutamine synthetase (GS) and glutamine transferase of rat cerebral cortex. Unlike the in vitro interaction of MSO with GS, the in vivo effects of the drug on this enzyme activity were irreversible, as judged by the recovery of normal enzyme maximal velocity upon in vitro incubation in the presence of excess substrate (glutamate or ATP). Conversely, identity of the in vitro and in vivo effects of the drug on glutamine transferase was noted, since the inhibitory effect of MSO could be readily reversed at high in vitro concentrations of glutamine under both conditions.

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