Liver glycogen synthase but not the muscle isoform differentiates between glucose 6-phosphate produced by glucokinase or hexokinase.
Using adenovirus-mediated gene transfer into FTO-2B cells, a rat hepatoma cell line, we have overexpressed hexokinase I (HK I), glucokinase (GK), liver glycogen synthase (LGS), muscle glycogen synthase (MGS), and combinations of each of the two glucose-phosphorylating enzymes with each one of the GS isoforms. FTO-2B cells do not synthesize glycogen even when incubated with high doses of glucose. Adenovirus-induced overexpression of HK I and/or LGS, two enzymes endogenously expressed by these cells, did not produce a significant increase in the levels of active GS and the total glycogen content. In contrast, GK overexpression led to the glucose-dependent activation of endogenous or overexpressed LGS and to the accumulation of glycogen. Similarly overexpressed MGS was efficiently activated by the glucose-6-phosphate (Glc-6-P) produced by either endogenous or overexpressed HK I and by overexpressed GK. These results indicate the existence of at least two pools of Glc-6-P in the cell, one of them is accessible to both isoforms of GS and is replenished by the action of GK, whereas LGS is excluded from the cellular compartment where the Glc-6-P produced by HK I is directed. These findings are interpreted in terms of the metabolic role that the two pairs of enzymes, HK I-MGS in the muscle and GK-LGS in the hepatocyte, perform in their respective tissues.
Gomis
Roger R
RR
Department of Biochemistry and Molecular Biology and Barcelona Science Park, Universitat de Barcelona, E-08028 Barcelona, Spain.
Cid
Emili
E
García-Rocha
Mar
M
Ferrer
Juan C
JC
Guinovart
Joan J
JJ
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D005941:Glucokinase / Q000502:physiology*; D019298:Glucose-6-Phosphate / Q000096:biosynthesis*; D006006:Glycogen Synthase / Q000502:physiology*; D006593:Hexokinase / Q000502:physiology*; D007527:Isoenzymes / Q000502:physiology*; D008099:Liver / Q000201:enzymology*; D009132:Muscles / Q000201:enzymology*; D051381:Rats; D014407:Tumor Cells, Cultured
D007527:Isoenzymes; D019298:Glucose-6-Phosphate; D006006:Glycogen Synthase; D006593:Hexokinase; D005941:Glucokinase