Fatty acids promote translocation of CTP:phosphocholine cytidylyltransferase to the endoplasmic reticulum and stimulate rat hepatic phosphatidylcholine synthesis.
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.