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.
Chan
Tom S
TS
Faculty of Pharmacy, University of Toronto, 19 Russell St Rm 522, Toronto, Ont, Canada M5S 2S2.
Wilson
John X
JX
O'Brien
Peter J
PJ
D000818:Animals; D001205:Ascorbic Acid / Q000096:biosynthesis*; D003994:Bucladesine / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D003958:Diamide / Q000494:pharmacology; D004229:Dithiothreitol / Q000494:pharmacology; D005632:Fructose / Q000494:pharmacology; D005978:Glutathione / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000378:metabolism*; D019803:Glutathione Disulfide / Q000378:metabolism; D006003:Glycogen / Q000378:metabolism*; D022781:Hepatocytes / Q000378:metabolism; D006536:Heptanes / Q000737:chemistry / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D048289:Imidazolidines; D007659:Ketones / Q000494:pharmacology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D014532:Uridine Diphosphate Glucose / Q000378:metabolism
D006536:Heptanes; D007093:Imidazoles; D048289:Imidazolidines; D007659:Ketones; D003958:Diamide; D005632:Fructose; D003994:Bucladesine; C018637:phorone; D006003:Glycogen; D000242:Cyclic AMP; C026411:sorbinil; D005978:Glutathione; D001205:Ascorbic Acid; D004229:Dithiothreitol; D019803:Glutathione Disulfide; D014532:Uridine Diphosphate Glucose