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.
Walkey
C J
CJ
Lipid and Lipoprotein Research Group and the Department of Biochemistry, University of Alberta, Edmonton, Alberta T6G 2S2, Canada.
Yu
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Agellon
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Vance
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DE
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