The regulation of fatty acid biosynthesis in rat hepatomas.

The dietary regulation of fatty acid synthesis de novo in two transplantable hepatomas, 7777 and 96188, has been studied by comparison of the acetyl coenzyme A carboxylase and fatty acid synthetase activities of tumor and host liver, both in animals fasted 48 hours and in those subsequently refed a fat-free diet for 48 hours. Neither acetyl-CoA carboxylase nor fatty acid synthetase of these hepatomas was subject to the changes in enzyme concentration normally observed in host liver following dietary alteration. Thus, in livers of refed animals acetyl-CoA carboxylase activity was 12to 29-fold greater than in the livers of fasted animals. Neither tumor studied showed any change in enzyme levels upon refeeding 48-hour fasted animals; 1.4 mpmoles of malonyl-CoA were formed per mg per min for hepatoma 7777 and 3.3 mpmoles of malonyl-CoA were formed per mg per min for hepatoma 96188. These activities of enzyme are Sto lo-fold greater than fasting levels in host liver. Fatty acid synthetase levels in host livers increased 1% to ZO-fold after refeeding. Again, neither tumor showed significant changes in enzyme activity upon refeeding fasted animals. Both acetyl-CoA carboxylase and fatty acid synthetase from hepatoma were inhibited by pahnityl-CoA despite their lack of response to dietary alteration. Acetyl-CoA carboxylase was purified 164-fold from rat liver and 67-fold from hepatoma 7777 to define further this lack of regulation. Studies of the purified enzymes disclosed that the tumor enzyme was essentially identical with that derived from liver in terms of heat inactivation, affinities for acetyl-CoA and ATP, activation and aggregation by citrate, product inhibition by malonyl-CoA, pH optima, and intrinsic specific activity as determined from biotin content. These experiments suggest that the acetyl-CoA carboxylase from the tumors is the same enzyme as that from host liver,