Synthesis of S-adenosylethionine by the gamma isozyme of methionine adenosyltransferase from Friend erythroleukemic cells.

Methionine adenosyltransferase (adenosine 5'-triphosphate-L-methionine S-adenosyltransferase, EC 2.5.1.6) was found to occur only as the gamma isozyme in Friend erythroleukemic cells. Enzyme activity in a dialyzed 105,000 X g supernatant was linear for at least 30 min and dependent on the amount of protein added. The Km for methionine was 10.6 microM. In the presence of 10% dimethyl sulfoxide, the enzyme activity was slightly inhibited and dithiothreitol was not required for maximum activity. These properties identify the methionine adenosyltransferase in Friend erythroleukemic cells as the gamma isozyme. L-Ethionine served as a substrate with a Km of 30 microM, and competitively inhibited the enzyme activity with a Ki of 150 microM. Friend erythroleukemic cells grown in the presence of ethionine accumulated S-adenosylethionine, which was dose and time dependent. Therefore, the gamma isozyme of methionine adenosyltransferase from Friend erythroleukemic cells utilize L-ethionine as substrate, resulting in an accumulation of S-adenosylethionine. These studies provide a mechanism by which ethionine through S-adenosylethionine may alter the methylation of DNA in Friend erythroleukemic cells.