EFFECTS OF CARBON TETRACHLORIDE ON THE METABOLISM OF LIVER GLYCOGEN IN THE RAT

¹ Department of Pharmacology, Division of Basic Health Sciences, Emory University, Atlanta, Georgia

Carbon tetrachloride has been reported by others to produce a rapid and prolonged depletion of liver glycogen in the rat. In the experiments reported here, starved rats given CCl₄ (290 µ/kg i.p.) 24 hours previously had hepatic glycogen concentrations lower than those of starved control rats. In addition, the treated rats did not deposit liver glycogen when refed a chow diet for three hours, a procedure which produced substantial accumulation of glycogen in livers of control rats. These changes in hepatic glycogen metabolism produced by CCl₄ were associated with a decreased activity of the I-form of glycogen transferase, an increased activity of glycogen phosphorylase and an inability to increase the activity of glycogen transferase I in response to feeding. The effects of CCl₄ treatment on hepatic glycogen metabolism were not due solely to structural damage of parenchymal cells since they were still found when the CCl₄-induced morphologic changes were substantially prevented by pretreatment with nicotinamide. The changes in activity of glycogen transferase and of phosphorylase produced by CCl₄ treatment were related to a decreased activity of glycogen transferase phosphatase and of phosphorylase phosphatase. These enzymes were first detectably lower than control values 12 hours after administration of CCl₄, and the changes were marked 24 hours after administration of CCl₄. Since CCl₄ decreases the synthesis of protein in the liver, the effect of cycloheximide on the activity of glycogen transferase phosphatase and phosphorylase phosphatase was determined. Cycloheximide decreased the activity of phosphorylase phosphatase 12 hours after treatment, but it did not affect the activity of transferase phosphatase at this time. Thus, the effects of CCl₄ on the storage of rat liver glycogen are the result of reciprocal changes in the activities of glycogen transferase and phosphorylase apparently due to decreased activities of their respective phosphatase enzymes. These latter changes might be caused in part by the ability of CCl₄ to decrease hepatic protein synthesis.