The biosynthesis of phosphatidylcholine by methylation of phosphatidylethanolamine derived from ethanolamine is not required for lipoprotein secretion by cultured rat hepatocytes.
The role that phosphatidylcholine biosynthesis plays in the assembly and secretion of lipoproteins has been investigated in rat hepatocytes, since phosphatidylcholine is the major phospholipid in all serum lipoproteins. Phosphatidylcholine in rat hepatocytes can be made via the CDPcholine pathway or by the methylation of phosphatidylethanolamine. A specific inhibitor of cellular transmethylation, 3-deazaadenosine (10 microM), has been incubated with rat hepatocytes, and we have shown that the biosynthesis of phosphatidylcholine via the methylation of phosphatidylethanolamine derived from ethanolamine was inhibited by greater than 95%. However, incubation of 3-deazaadenosine with cultured rat hepatocytes for up to 18 h did not affect the secretion of any of the apoproteins into VLDL, LDL, HDL fractions or a fraction with density greater than 1.18 g/ml (albumin was the major protein). Nor was there any effect by 3-deazaadenosine on the amount of phosphatidylcholine secreted into the culture medium or into VLDL or HDL. After 18 h the amount of phosphatidylethanolamine that accumulated in the cells was doubled by treatment with 3-deazaadenosine, and the amount of phosphatidylethanolamine secreted into the medium was increased by approximately 70%. It is thus apparent that the synthesis of phosphatidylcholine from ethanolamine is not required for lipoprotein secretion by rat hepatocytes.
D000818:Animals; D001053:Apolipoproteins / Q000378:metabolism; D002478:Cells, Cultured; D003566:Cytidine Diphosphate Choline / Q000378:metabolism; D004983:Ethanolamines / Q000378:metabolism*; D005227:Fatty Acids / Q000378:metabolism; D005260:Female; D008074:Lipoproteins / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D008745:Methylation; D010713:Phosphatidylcholines / Q000096:biosynthesis*; D010714:Phosphatidylethanolamines / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D014372:Tubercidin / Q000494:pharmacology
D001053:Apolipoproteins; D004983:Ethanolamines; D005227:Fatty Acids; D008074:Lipoproteins; D010713:Phosphatidylcholines; D010714:Phosphatidylethanolamines; C018258:3-deazaadenosine; D003566:Cytidine Diphosphate Choline; D014372:Tubercidin