Shared control of hepatic glycogen synthesis by glycogen synthase and glucokinase.
We have used recombinant adenoviruses (AdCMV-RLGS and AdCMV-GK) to overexpress the liver isoforms of glycogen synthase (GS) and glucokinase (GK) in primary cultured rat hepatocytes. Glucose activated overexpressed GS in a dose-dependent manner and caused the accumulation of larger amounts of glycogen in the AdCMV-RLGS-treated hepatocytes. The concentration of intermediate metabolites of the glycogenic pathway, such as glucose 6-phosphate (Glc-6-P) and UDP-glucose, were not significantly altered. GK overexpression also conferred on the hepatocyte an enhanced capacity to synthesize glycogen in response to glucose, as described previously [Seoane, Gómez-Foix, O'Doherty, Gómez-Ara, Newgard and Guinovart (1996) J. Biol. Chem. 271, 23756-23760], although, in this case, they accumulated Glc-6-P. When GS and GK were simultaneously overexpressed, the accumulation of glycogen was enhanced in comparison with cells overexpressing either GS or GK. Our results are consistent with the hypothesis that liver GS catalyses the rate-limiting step of hepatic glycogen synthesis. However, hepatic glycogen deposition from glucose is submitted to a system of shared control in which the 'controller', GS, is, in turn, controlled by GK. This control is indirectly exerted through Glc-6-P, which 'switches on' GS dephosphorylation and activation.
Gomis
R R
RR
Departament de Bioquímica i Biologia Molecular, Universitat de Barcelona, Martí i Franquès, 1, E-08028 Barcelona, Spain.
Ferrer
J C
JC
Guinovart
J J
JJ
D000256:Adenoviridae / Q000235:genetics / Q000502:physiology; D000818:Animals; D015967:Gene Expression Regulation, Viral / Q000502:physiology; D005941:Glucokinase / Q000378:metabolism*; D006006:Glycogen Synthase / Q000378:metabolism*; D022781:Hepatocytes / Q000201:enzymology / Q000378:metabolism; D019344:Lactic Acid / Q000096:biosynthesis; D008112:Liver Glycogen / Q000096:biosynthesis*; D008297:Male; D051381:Rats; D017208:Rats, Wistar
D008112:Liver Glycogen; D019344:Lactic Acid; D006006:Glycogen Synthase; D005941:Glucokinase