Induction of rat liver phospho enolpyruvate carboxykinase (GTP) by cyclic AMP during starvation. The permissive action of glucocorticoids

Abstract

The effect of starvation on the activity of hepatic phospho enolpyruvate carboxykinase (GTP: oxaloacetate carboxy-lyase (transphosphorylating), EC 4.1.1.32), and on the response of the enzyme to N 6- O 2′-dibutyryl adenosine 3′,5′-monophosphate was investigated in intact and glucocorticoid-deprived rats. In the liver of intact animals, starvation produced a rapid increase in the concentration of cyclic AMP and a corresponding increase in the activity of phospho enolpyruvate carboxykinase. The kinetics of both changes were not affected by adrenalectomy. Injection of N 6- O 2′-dibutyryl adenosine 3′, 5′-monophosphate into intact starved rats resulted in an immediate, dramatic increase in phospho enolpyruvate carboxykinase activity above the starvation level. Adrenalectomy completely blocked the response of the enzyme to the cyclic nucleotide. Restoration of hydrocortisone to the adrenalectomized animals restored the full N 6- O 2′-dibutyryl adenosine 3′,5′-monophosphate effect a lag period of 2 h. The physiological significance of these findings is considered. The data are interpreted with regard to the current hypothesis that glucocorticoids promote an increase in translatable phospho enolpyruvate carboxykinase mRNA, while cyclic AMP enhances the translation of preexisting specific mRNA templates.