Asymmetry of phospholipid biosynthesis

Abstract

THE asymmetrical distribution of phospholipids in the membrane of the red blood cell^1–3 and other membranes^4,5 is well documented. How this asymmetry arises in these membranes is an obvious question which remains unanswered. One explanation is that the enzymes that catalyse the last step in the synthesis of the phospholipids are unevenly distributed on both sides of the membrane where biosynthesis occurs. The phospholipids that are produced by these enzymes would be released on to each side of the lipid bilayer and thus account for lipid asymmetry. A necessary corollary would be that this asymmetry of the phospholipids would be preserved in the movement of lipids to other membranes in the cell. Initial reports on the lack of transbilayer movement of phospholipids in artificial membranes^6,7 and membranes of animal viruses⁸ has made an uneven distribution of phospholipid biosynthetic enzymes an attractive hypothesis. Recent reports, however, have documented the transbilayer movement of phospholipids in the red blood cell membrane^9–11 and the membrane of Bacillus megaterium¹². Although the mechanism for this transbilayer movement of phospholipids has yet to be elucidated, it is no longer necessary to explain lipid asymmetry by the uneven distribution of the phospholipid biosynthetic enzymes on both sides of the membrane. We summarise here our evidence that the enzymes that help to produce phosphatidylcholine and phosphatidylethanolamine are located exclusively on the cytoplasmic surface of the endoplasmic reticulum of rat liver and not on both sides of the membrane.