SUBSTRATE AND HORMONE REGULATION OF PALMITOYL-COA SYNTHETASE IN 7800-C1 MORRIS HEPATOMA-CELLS AND CULTURED RAT HEPATOCYTES

The effects of tetradecylthioacetic acid (TTA), insulin and dexamethas one on palmitoyl-CoA synthetase activity and its mRNA both in 7800 C1 hepatoma cells and cultured rat hepatocytes were studied. (1) When the hepatoma cells were cultivated in the presence of fatty acids or alky l thioacetic acids (3-thia fatty acids) palmitoyl-CoA synthetase activ ity was increased several fold. The stronger effect was obtained with TTA, which also increased long-chain acyl-CoA synthetase mRNA signific antly. TTA has no inducing effect on butyryl-CoA synthetase and little effect on octanoyl-CoA synthetase in the same cells. Dexamethasone al so had inducing effect on palmitoyl-CoA synthetase in the hepatoma cel ls. Insulin counteracted the induction given by TTA. All of these regu lation actions take place at the pretranslational level. (2) In isolat ed hepatocytes the activity of palmitoyl-CoA synthetase was much highe r than in hepatoma cells, but it was lost rapidly in culture. The loss of the enzyme activity was slowed down in the presence of TTA and ins ulin, either alone or combined. Dexamethasone combined with TTA revers ed the loss of enzyme activity, while dexamethasone alone even increas ed the loss. Analysis of palmitoyl-CoA synthetase mRNA shows that TTA prevents the loss of the enzyme activity by inducing mRNA of the enzym e, dexamethasone enhances the effect of TTA, while insulin stabilizes the enzyme activity in the cultured cells without increasing the mRNA level.