Enzymatic synthesis and rapid translocation of phosphatidylcholine by two methyltransferases in erythrocyte membranes.

Abstract

The synthesis of phosphatidylcholine from phosphatidylethanolamine is carried out by 2 methyltransferases in [rat] erythrocyte membranes. The 1st enzyme uses phosphatidylethanolamine as a substrate, requires Mg2+ and has a high affinity for the methyl donor, S-adenosyl-L-methionine. The 2nd enzyme methylates phosphatidyl-N-monomethylethanolamine to phosphatidylcholine and has a low affinity for S-adenosyl-L-methionine. The 1st enzyme is localized on the cytoplasmic side of the membrane and the 2nd enzyme faces the external surface. This asymmetric arrangement of the 2 enzymes across the membrane makes possible the stepwide methylation of phosphatidylethanolamine localized on the cytoplasmic side and facilitates the rapid transmembrane transfer of the final product, phosphatidylcholine, to the external surface of the membrane. A mechanism for an enzyme-mediated flip-flop of phospholipids from the cytoplasmic to the outer surface of erythrocyte membranes is described.