Methionine sulfoximine, inhibition glutamine synthesis

More recently Braganca, Faulkner, and Quastel (B15) showed that this inhibition of acetylcholine synthesis in brain slices by ammonia is consistent only in the diminution of bound acetylcholine. They further showed that the addition of inhibitors of glutamine synthesis, such as methionine sulfoxide, ethionine sulfoxide, and methionine sulfoximine (the toxic product, causing convulsions, formed in flour chemically aged with nitrogen trichloride) would partially reverse the ammonium inhibition. These observations were confirmed and extended to a wide variety of ATP-requiring reactions by Weil-Malherbe. In support of this suggestion was the observation that ammonia is taken up by the brain in hepatic coma (B8). The observations are valid and have been confirmed, but the interpretation of the data and the hypothesis are questionable. A quantitative basis for the evaluation of this mechanism can... 

Alanine appears to be formed primarily by alanine dehydrogenase in A. cylindrica, C. licheniformey P. boryanumy and A. nidulanSy because the inhibition of formation of glutamate and glutamine by methionine sulfoximine is not accompanied by a comparable inhibition in the formation of alanine (Table I). Moreover, alanine formation by these species was not reduced in the presence of aminooxy acetate, an inhibitor of amino transfer reactions (I3,J4). However, in A. variabilis alanine appears to be formed by a transamination reaction, because synthesis of [ N]alanine from was strongly inhibited in the presence of... 

The sequential labeling of first citrulline and then arginine are consistent with the idea that citrulline is a substrate for the synthesis of arginine. In cyanobacteria, citrulline appears to be formed by the condensation of carbamyl phosphate with ornithine (27). The inhibition of formation of citrulline (and arginine) by methionine sulfoximine, azaserine, and aminooxy acetate could be due to the reduced formations of ornithine from glutamate and carbamyl phosphate from glutamine. In... 

SELECTIVE INHIBITION OF THE SYNTHESIS OF GLUTAMINE AND GLUTATHIONE BY ANALOGS OF METHIONINE SULFOXIMINE... 

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