Evidence that the enzymes involved in the methylation of phosphatidylethanolamine are on the external side of the microsomal vesicles.

The topology of the phosphatidylethanolamine (PE)-N-methyltransferase(s) on rat liver microsomes has been studied. The activity for the conversion of PE to phosphatidylcholine decreased by 50% after 2 min of exposure of the microsomes to trypsin and was virtually eliminated with 15 min. When exogenous monomethyl-PE or dimethyl-PE were incubated with microsomes, the formation of dimethyl-PE and phosphatidylcholine were also eliminated as a result of trypsin digestion. During the experiments the microsomes remained intact, since the latency of the mannose-6-phosphate phosphohydrolase remained approx. 90%. It is concluded that the active site(s) of the enzyme(s), or portions of the enzyme(s) indispensable to its activity, are present at the cytosolic side of the microsomes.