Regulation of the phosphatidylethanolamine methylation pathway in Saccharomyces cerevisiae.

1. Phosphatidyl-N-methylethanolamine methyltransferase mutants of Saccharomyces cerevisiae were isolated. Genetic analysis showed that phosphatidylethanolamine methyltransferase and phosphatidyl-N-methylethanolamine methyltransferase are coded for by separate genes. Phosphatidyl-N-methylethanolamine methyltransferase activity and phosphatidyl-N,N-dimethylethanolamine methyltransferase activity appeared to be catalyzed by the same enzyme. 2. Phosphatidyl-N-methylethanolamine methyltransferase was found to be repressed by myo-inositol and choline. Both myo-inositol and choline at concentrations of 10 micrograms/ml were required for repression. The decreased enzyme level was restored by the removal of myo-inositol or choline or both. 3. Both myo-inositol and choline were required for the maximum repression of phosphatidylethanolamine methyltransferase in wild-type cells. In contrast, choline was not required for the repression of the enzyme in mutant strain 172. This was due to a single nuclear gene mutation in the genome of strain 172. 4. The activity of the phosphatidylethanolamine methylation pathway in cells decreased with time on incubation of cells with myo-inositol and choline, myo-Inositol could not be replaced by other structurally related compounds, such as scyllo-inositol or mannitol. 5. The physiological significance of the repression of the phosphatidylethanolamine methylation pathway is discussed with respect to the mechanism for maintaining the contents of phosphatidylethanolamine and phosphatidylcholine at normal levels.