Investigations will continue which are directed at the delineation of the mechanisms by which insulin and glucagon effect the short-term and long-term regulation of the activities of acetyl-CoA carboxylase, fatty acid synthetase and beta-hydroxy-beta-methylglutaryl coenzyme A (HMG-CoA) reductase in mammalian liver. These studies will be carried out with isolated and cultured liver cells and with whole animals. Studies on the fatty acid synthetase complex will concentrate on the development of methods of purification and assay of mRNA coding for this enzyme. This assay procedure will then be used to determine the effect of insulin on the quantity of this mRNA in rat liver. Studies on acetyl-CoA carboxylase will concentrate on the purification to homogeneity of an inactivator and activator of this enzyme. These studies will be followed with ones on the effects of insulin and glucagon on the activities of these regulators of acetyl-CoA carboxylase activity. If inulin and glucagon are found to regulate the activities of these proteins, the mechanisms of their action will be sought. Studies on HMG-CoA reductase will attempt to delineate whether the effect of insulin on the activity of this enzyme is due to a change in quantity of enzyme or a change in activity of pre-existing enzyme. When this question is answered, attempts will be made to delineate further the mechanism of insulin action on this enzyme.