SUMMARY: α-Methylmethionine is a potent growth-inhibitory analogue of methionine producing an immediate effect on the growth rate of at very low concentrations. Under certain conditions inhibition was transient, apparently due to an adaptation by the organisms. The analogue did not repress the synthesis of the methionine-forming enzymes but mimicked methionine as a feedback inhibitor of homoserine--trans-succinylase, acting on the enzyme at even lower concentrations than did methionine itself. Comparison of the effects on enzyme activity and growth rate leads to the conclusion that such enzyme inhibition is the basis of the effect of analogue on growth. Certain other compounds related to methionine also inhibited homoserine--trans-succinylase and of these D-methionine, DL-homocysteine and -acetylmethionine probably caused inhibition after conversion to L-methionine.

α-Methylmethionine markedly inhibited the formation of infective phage after irradiation of HfrH(λ); methionine annulled the effect and allowed phage development to occur. The analogue was not incorporated into proteins in place of methionine, nor did it interfere with the incorporation of added methionine. Protein synthesis was inhibited by the analogue only when the process was dependent on methionine formation.


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