Biochemical and evolutionary significance of phospholipid methylation.
All nucleated mammalian cells synthesize phosphatidylcholine from choline via the CDP-choline pathway. Hepatocytes have a second pathway for the synthesis of phosphatidylcholine, a stepwise methylation of phosphatidylethanolamine, catalyzed by phosphatidylethanolamine N-methyltransferase and encoded by the Pempt gene. We report that when Pempt-deficient mice were fed a choline-deficient diet for 3 days, severe liver pathology occurred apparently due to a lack of phosphatidylcholine biosynthesis. 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 maintained during evolution to provide phosphatidylcholine when dietary choline is insufficient, as might occur during starvation or pregnancy.
Lipid and Lipoprotein Research Group and the Department of Biochemistry, University of Alberta, Edmonton, Alberta T6G 2S2, Canada.
C J
CJ
Walkey
L
L
Yu
L B
LB
Agellon
D E
DE
Vance
D000818:Animals; D001647:Bile Acids and Salts / Q000097:blood; D002784:Cholesterol / Q000097:blood; D002796:Choline Deficiency / Q000378:metabolism*; D003566:Cytidine Diphosphate Choline / Q000378:metabolism; D004032:Diet; D005260:Female; D008074:Lipoproteins / Q000097:blood; D008099:Liver / Q000737:chemistry / Q000473:pathology*; D008297:Male; D008745:Methylation; D008780:Methyltransferases / Q000172:deficiency* / Q000235:genetics; D051379:Mice; D008817:Mice, Mutant Strains; D010713:Phosphatidylcholines / Q000096:biosynthesis*; D050918:Phosphatidylethanolamine N-Methyltransferase; D010714:Phosphatidylethanolamines / Q000378:metabolism*; D000637:Transaminases / Q000097:blood; D014280:Triglycerides / Q000097:blood
D001647:Bile Acids and Salts; D008074:Lipoproteins; D010713:Phosphatidylcholines; D010714:Phosphatidylethanolamines; D014280:Triglycerides; D003566:Cytidine Diphosphate Choline; D002784:Cholesterol; D008780:Methyltransferases; D050918:Phosphatidylethanolamine N-Methyltransferase; D000637:Transaminases