title: Fatty acids promote translocation of CTP:phosphocholine cytidylyltransferase to the endoplasmic reticulum and stimulate rat hepatic phosphatidylcholine synthesis.
abstract: The mechanism by which fatty acids stimulate the biosynthesis of phosphatidylcholine has been studied in cultured rat hepatocytes. Long chain fatty acids (1 mM) stimulated approximately 1.9-fold [methyl-3H] choline incorporation from phosphocholine into phosphatidylcholine by isolated hepatocytes. Oleate and palmitate (4 mM) enhanced phosphatidylcholine production by 3- and 2.2-fold, respectively. Stimulation of phosphatidylcholine synthesis by oleate was evident within 30 min after addition of the fatty acid to the hepatocyte medium. The effect could be correlated with a doubling of the microsomal CTP:phosphocholine cytidylyltransferase activity. Additional evidence for a direct effect by fatty acids and their CoA derivatives on the cytidylyltransferase was obtained in vitro. Arachidonate, oleate and palmitate (0.1 mM) stimulated rat liver cytosolic cytidylyltransferase activity 4.1-, 3.5- and 3.2-fold, respectively. Activation by oleate was accompanied by a 3.6-fold reduction in the apparent Km of the cytidylyltransferase for CTP and aggregation of the enzyme to high molecular weight species. Acceleration of the cytidylyltransferase reaction by fatty acids provides a positive feed-forward mechanism for regulation of phosphatidylcholine anabolism.
mesh_terms: D000214:Acyl Coenzyme A / Q000494:pharmacology; D000818:Animals; D001692:Biological Transport; D002478:Cells, Cultured; D019916:Choline-Phosphate Cytidylyltransferase; D004721:Endoplasmic Reticulum / Q000201:enzymology*; D005230:Fatty Acids, Nonesterified / Q000494:pharmacology*; D007700:Kinetics; D008099:Liver / Q000201:enzymology*; D009713:Nucleotidyltransferases / Q000378:metabolism*; D019301:Oleic Acid; D009829:Oleic Acids / Q000494:pharmacology; D010713:Phosphatidylcholines / Q000096:biosynthesis*; D051381:Rats
chemical_list: D000214:Acyl Coenzyme A; D005230:Fatty Acids, Nonesterified; D009829:Oleic Acids; D010713:Phosphatidylcholines; C017585:oleoyl-coenzyme A; D019301:Oleic Acid; D009713:Nucleotidyltransferases; D019916:Choline-Phosphate Cytidylyltransferase