Fructose effect to suppress hepatic glycogen degradation.
The effect of fructose on glycogen degradation was examined by measuring the flux of 14C from prelabeled glycogen in perfused rat livers. During 2-h refeeding of 24-h-fasted rats, newly synthesized hepatic glycogen was labeled by intraperitoneal injection of [U-14C] galactose (0.1 mg and 0.02 microCi/g of body weight). The livers of refed rats were then perfused in a nonrecirculating fashion for an initial 30 min with glucose alone (10 mM) for the following 60 min with glucose (10 mM) without (n = 5) or with fructose (1, 2, or 10 mM; n = 5 for each). When livers were exposed to fructose, release of label into the perfusate immediately declined and remained markedly suppressed through the end of perfusion (p less than 0.05). The suppression was dose-dependent; at steady state (50-70 min), label release was suppressed 45, 64, and 72% by 1, 2, and 10 mM fructose, respectively (p less than 0.0001). Suppression was not accompanied by significant changes in the activities of glycogen synthase or phosphorylase assessed in vitro. These results suggest the existence of allosteric inhibition of phosphorylase in the presence of fructose. Fructose 1-phosphate (Fru-1-P) accumulated in proportion to fructose (0.11 +/- 0.01 without fructose, 0.86 +/- 0.03, 1.81 +/- 0.18, and 8.23 +/- 0.60 mumol/g of liver with 1, 2, and 10 mM fructose, respectively; p less than 0.0001). Maximum inhibition of label release was 82%; the Fru-1-P concentration for half inhibition was 0.57 mumol/g of liver, well within the concentration of Fru-1-P attained during refeeding. We conclude that fructose enhances net glycogen accumulation in liver by suppressing glycogenolysis and that the suppression is presumably caused by allosteric inhibition of phosphorylase by Fru-1-P.
D000818:Animals; D005632:Fructose / Q000494:pharmacology*; D005943:Gluconeogenesis; D006006:Glycogen Synthase / Q000378:metabolism; D007700:Kinetics; D007773:Lactates / Q000096:biosynthesis; D019344:Lactic Acid; D008099:Liver / Q000187:drug effects; D008112:Liver Glycogen / Q000378:metabolism*; D008297:Male; D008433:Mathematics; D010477:Perfusion; D010762:Phosphorylase a / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
D007773:Lactates; D008112:Liver Glycogen; D005632:Fructose; D019344:Lactic Acid; D010762:Phosphorylase a; D006006:Glycogen Synthase