BIOCHEMICAL AND EVOLUTIONARY SIGNIFICANCE OF PHOSPHOLIPID METHYLATION

All nucleated mammalian cells synthesize phosphatidylcholine from chol ine via the CDP-choline pathway. Hepatocytes have a second pathway for the synthesis of phosphatidylcholine, a stepwise methylation of phosp hatidylethanolamine, catalyzed by phosphatidylethanolamine N-methyltra nsferase and encoded by the Pempt gene. We report that when Pempt defi cient mice were fed a choline-deficient diet for 3 days, severe liver pathology occurred apparently due to a lack of phosphatidylcholine bio synthesis. The hepatic concentration of phosphatidylcholine decreased by 50% compared with wild type mice on the diet. The levels of plasma triacylglycerols and cholesterol were decreased by greater than 90% in the Pempt-deficient mice. We suggest that the Pempt gene has been mai ntained during evolution to provide phosphatidylcholine when dietary c holine is insufficient, as might occur during starvation or pregnancy.