Carbamoyl phosphate and ureagenesis are not involved in amino‐acid‐stimulated glycogenesis

Abstract

Amino acids are known to stimulate glycogen synthesis via an increase in cell volume [Baquet, A., Hue, L., Meijer, A. J., van Woerkom, G. M. & Plomp, P. J. A. M. (1990) Chem. 268, 16298-163011. To further examine the role carbamoyl phosphate may play in glycogenesis, isolated hepatocytes were incubated under a variety of conditions to manipulate ureagenesis, glycogenesis and carbamoyl-phosphate levels. Our data indicate that carbamoyl-phosphate levels do not correlate with amino-acid-stimulated glycogenesis and that ureagenesis and glycogenesis are not competing metabolic pathways.Amino acids are known stimulators of glycogen synthesis in rat hepatocytes [l, 21. Since amino acid analogues [3] and hypotonicity [4] are both able to mimic this effect, it appears that the underlying mechanism is not necessarily related to intermediates of amino acid metabolism. There is strong evidence that cell swelling, which accompanies the sodium-coupled transport of certain amino acids into the cell [5], evokes a stimulatory effect upon glycogen synthesis [4]. Furthermore, it has been demonstrated that this stimulation is achieved by a lowering of the intracellular chloride concentration, a result of regulatory volume decrease after cell swelling [6]. Since chloride ions are inhibitory to glycogen synthase phosphatase, such a decrease leads to an enhancement in the activation state of glycogen synthase and thereby induces the stimulation of glycogen synthesis [6].A recent study [7] on the relationship between glycogenesis and ureagenesis with proline and glutamine as substrates, however, offers a possible extension to the current ideas on the swelling-induced stimulation of glycogen synthesis. Bode and Nordlie [7] have proposed that carbamoyl phosphate, an intermediate of amino acid metabolism and ureagenesis, may play a key role in the stimulation of glycogen synthesis by proline. According to this study, carbamoyl phosphate can function as a substrate for glucose 6-phosphatase to form glucose 6-phosphate, an allosteric activator of glycogen synthase b, and thus lead to a stimulation of glycogen synthesis.Correspondence to