The reaction between ATP and methionine, catalyzed by methionine adenosyl-transferase (ATP:l-methionine S-adenosyltransferase, E.C. 2.5.1.6) was studied. Pan and Tarver (3) recently compared several different analogues of methionine as substrates for rat-liver methionine adenosyltransferase. In the present study analogues of methionine were used to inhibit the reaction to gain a better understanding of the specificity of the enzyme and the binding of methionine to the enzyme. Ethionine and S-trifluoromethyl-homocysteine inhibited the activation of methionine by rat-liver enzyme. The activation of methionine by extracts of the enzyme from Salmonella typhimurium was not inhibited by ethionine. The conformation of methionine required by the different enzymes, trans- or cis-like forms, could account for these results. Methionine activation showed higher inhibition only by those analogues of methionine that act as substrates. α-Methylmethionine and norleucine slightly inhibited the activation of methionine with rat-liver enzyme. S-Methyl and S-ethyl cysteine were also poor inhibitors. Ethionine and S-trifluoromethyl-homocysteine were shown to be competitive inhibitors of methionine activation. S-Adenosylmethionine and S-adenosylethionine were better inhibitors of S-adenosylmethionine formation than were the analogues of methionine. The end-product inhibition observed in these experiments suggest a control mechanism for the formation of S-adenosylmethionine. © 1969.
