Glucose 6-phosphate causes translocation of phosphorylase in hepatocytes and inactivates the enzyme synergistically with glucose

Biochem J. 2004 Jan 1;377(Pt 1):195-204. doi: 10.1042/BJ20031191.


The role of glucose 6-P (glucose 6-phosphate) in regulating the activation state of glycogen synthase and its translocation is well documented. In the present study, we investigated the effects of glucose 6-P on the activation state and compartmentation of phosphorylase in hepatocytes. Glucose 6-P levels were modulated in hepatocytes by glucokinase overexpression or inhibition with 5-thioglucose and the effects of AMP were tested using AICAR (5-aminoimidazole-4-carboxamide 1-beta-D-ribofuranoside), which is metabolized to an AMP analogue. Inhibition of glucokinase partially counteracted the effect of glucose both on the inactivation of phosphorylase and on the translocation of phosphorylase a from a soluble to a particulate fraction. The increase in glucose 6-P caused by glucokinase overexpression caused translocation of phosphorylase a to the pellet and had additive effects with glucose on inactivation of phosphorylase. It decreased the glucose concentration that caused half-maximal inactivation from 20 to 11 mM, indicating that it acts synergistically with glucose. AICAR activated phosphorylase and counteracted the effect of glucose 6-P on phosphorylase inactivation. However, it did not counteract translocation of phosphorylase by glucose 6-P. Glucose 6-P and AICAR had opposite effects on the activation state of glycogen synthase, but they had additive effects on translocation of the enzyme to the pellet. There was a direct correlation between the translocation of phosphorylase a and of glycogen synthase to the pellet, suggesting that these enzymes translocate in tandem. In conclusion, glucose 6-P causes both translocation of phosphorylase and inactivation, indicating a more complex role in the regulation of glycogen metabolism than can be explained from regulation of glycogen synthase alone.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aminoimidazole Carboxamide / analogs & derivatives*
  • Aminoimidazole Carboxamide / pharmacology
  • Animals
  • Cell Compartmentation
  • Cells, Cultured
  • Glucokinase / metabolism
  • Glucose / pharmacology*
  • Glucose-6-Phosphate / physiology*
  • Glycogen Synthase / metabolism
  • Hepatocytes / drug effects
  • Hepatocytes / enzymology*
  • Hepatocytes / metabolism
  • Male
  • Phosphorylases / metabolism*
  • Protein Transport
  • Rats
  • Rats, Wistar
  • Ribonucleotides / pharmacology


  • Ribonucleotides
  • Aminoimidazole Carboxamide
  • Glucose-6-Phosphate
  • Phosphorylases
  • Glycogen Synthase
  • Glucokinase
  • AICA ribonucleotide
  • Glucose