Glycogenolysis is directed towards ascorbate synthesis by glutathione conjugation

Using isolated rat hepatocytes we have shown that glutathione (GSH) depletion by glutathione-S-transferase (GST)-catalyzed conjugation with 1-bromoheptane or phorone was accompanied by a significant elevation in ascorbate synthesis. Glycogenolysis was also stimulated without a significant rise in glucose synthesis. Furthermore, when glycogenolysis was stimulated in control hepatocytes by increasing intracellular cAMP levels (with glucagon or dibutyryl cAMP), cellular glucose levels, but not ascorbate levels, increased. These data suggest that GSH depletion can stimulate ascorbate synthesis independently of glucose synthesis and that hepatocytes can direct glycogenolysis towards ascorbate synthesis during GSH conjugation.