The possible functional significance of phosphatidylethanolamine methylation

Abstract

The conversion of phosphatidylethanolamine to phosphatidylcholine was first reported in rat liver microsomes by Bremer and Greenberg¹. The reaction requires three successive methylations of the ethanolamine moiety by S-adenosyl-methionine. The highest activity for this enzyme has been found in liver microsomes and the enzyme from rat liver was recently solubilized and partially purified². Although the activity is highest in liver, it is the minor pathway in this tissue for the synthesis of phosphatidylcholine³. The enzyme has recently been identified in bovine adrenal medulla⁴ and reports exist on the activity of phosphatidylethanolamine methyltransferase in erythrocyte ghosts⁵, reticulocyte ghosts^6,7 and mammary gland membranes⁸. In view of the relatively minor importance of the methylation pathway in phosphatidylcholine biosynthesis in liver, we were intrigued by the reports of significant physiological changes attributed to phospholipid methylation^6–9. Calculations reported here show that this enzymatic activity in reticulocytes, erythrocytes and mammary gland membranes is 0.1% of that observed in liver microsomes. Furthermore, in conditions where marked changes in microviscosity of the erythrocyte membrane were observed, only extremely small amounts of phosphatidylethanolamine were methylated⁹. For these and other reasons, there is considerable doubt that methylation of phosphatidylethanolamine could account for the many physiological responses attributed to this activity.