In vivo studies have shown that glutathione deficiency induces ascorbate synthesis in mouse liver. More recently we have reported that ascorbate production is connected to hepatic glycogenolysis. In the present study a possible link between these two phenomena was investigated. GSH deficiency caused by various agents increased ascorbate synthesis with a simultaneous elevation of glycogen breakdown in isolated murine hepatocytes. Addition of UDP-glucose to permeabilised hepatocytes or gulonolactone to intact cells increased ascorbate synthesis independently of glutathione depletion. Inhibition of glycogenolysis by fructose prevented the stimulation of ascorbate synthesis caused by glutathione consumption. Reduction of oxidized glutathione by dlthiothreitol prevented the elevation of glycogenolysis and ascorbate synthesis in diamide or menadione treated hepatocytes highlighting the effect of oxidized glutathione on glycogenolysis. Our results suggest that glutathione and ascorbate are linked not only via redox coupling but also via metabolic connection. The change of GSH/GSSG ratio proves to be sufficient precondition of altering glycogenolysis and the consequent glycogenolysis-linked ascorbate synthesis.
|Publication status||Published - Dec 1 1997|
ASJC Scopus subject areas
- Molecular Biology