Alterations by clofibric acid of metabolism of phosphatidylethanolamine in rat-liver.
Metabolic changes induced by p-chlorophenoxyisobutyric acid (clofibric acid) in hepatic phosphatidylethanolamine (PtdEtn) were studied. The treatment of rats with clofibric acid increased the hepatic concentrations of phosphatidylcholine (PtdCho), PtdEtn and phosphatidylinositol (PtdIns), but not phosphatidylserine (PtdSer). Among the phospholipids, the extent of increase of PtdEtn was the most prominent (1.91-fold on the basis of g liver and 2.73-fold on the basis of whole liver). Of the enzymes which are involved in the synthesis de novo of PtdEtn, the activity of cytidine 5'-triphosphate (CTP): phosphoethanolamine cytidylytransferase was reduced by the administration of clofibric acid to rats. The treatment of rats with this drug significantly decreased the serum concentration of free ethanolamine. Clofibric acid enhanced the activity of PtdSer decarboxylase and depressed the N-methylation in vivo of PtdEtn by inhibiting N-methyltransferase. Moreover, clofibric acid significantly depressed the turnover of PtdEtn, which was labeled in vivo with [3H]glycerol. These results suggest that, under the influence of clofibric acid, hepatocytes facilitate the pathway PtdCho-->PtdSer-->PtdEtn and reduce the turnover of PtdEtn, resulting in an expanded cellular pool of PtdEtn.
Research Laboratories, Torii Pharmaceutical Co., Ltd., Chiba, Japan.
H
H
Mizuguchi
Y
Y
Kawashima
D000818:Animals; D000924:Anticholesteremic Agents / Q000494:pharmacology*; D002262:Carboxy-Lyases / Q000378:metabolism; D002995:Clofibric Acid / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D008745:Methylation; D008780:Methyltransferases / Q000378:metabolism; D010713:Phosphatidylcholines / Q000378:metabolism; D050918:Phosphatidylethanolamine N-Methyltransferase; D010714:Phosphatidylethanolamines / Q000378:metabolism*; D010716:Phosphatidylinositols / Q000378:metabolism; D010718:Phosphatidylserines / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D000924:Anticholesteremic Agents; D010713:Phosphatidylcholines; D010714:Phosphatidylethanolamines; D010716:Phosphatidylinositols; D010718:Phosphatidylserines; D002995:Clofibric Acid; D008780:Methyltransferases; D050918:Phosphatidylethanolamine N-Methyltransferase; D002262:Carboxy-Lyases; C022353:phosphatidylserine decarboxylase