Glucose 6-phosphate plays a central role in the regulation of glycogen synthesis in a glycogen-storing liver cell line.
Two substrains of the epithelial liver cell line C1I, one storing large amounts of glycogen, the other one being very poor in glycogen were used as a model for studying glycogen synthesis. The glycogen content of glycogen-rich cells doubled during the proliferative phase and remained high in plateau phase although glycogen synthase I activity was not significantly altered during growth cycle and was too low to account for the increase in glycogen. However, the activity of the glucose 6-phosphate (Glc6-P)-dependent synthase rose continuously during growth cycle, and intracellular Glc6-P-concentration increased about 10-fold in log phase cells to 0.72 mumol g-1 wet weight. A0.5 of synthase for Glc6-P was 0.79 mM. It was also found that in contrast to the enzyme from normal liver, glycogen phosphorylase a from C1I cells was inhibited by Glc6-P, the apparent Ki being 0.45 mM. It was concluded that glycogen accumulation in C1I cells was due to stimulation of synthase and inhibition of phosphorylase by Glc6-P. Findings from the glycogen-poor cell line which revealed similar specific activities of synthase and phosphorylase but only low Glc6-P (0.056 mumol g-1 wet weight) supported this conclusion. Addition of glucose to starved cells resulted in a transient activation of synthase in both cell lines. Net glycogen synthesis, was, however, only observed in the cells with a high Glc6-P-content. Thus, modulation of synthase and phosphorylase by Glc6-P and not activation/inactivation of the enzymes seems to play a predominant role in glycogen accumulation in this cell line.
Mayer
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Institut für Experimentelle Pathologie, Deutsches Krebsforschungszentrum, Heidelberg, FRG.
Letsch
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D000818:Animals; D002455:Cell Division / Q000502:physiology; D002460:Cell Line; D005947:Glucose / Q000494:pharmacology; D019298:Glucose-6-Phosphate; D005958:Glucosephosphates / Q000378:metabolism*; D006006:Glycogen Synthase / Q000378:metabolism; D008099:Liver / Q000166:cytology / Q000201:enzymology / Q000378:metabolism*; D008112:Liver Glycogen / Q000096:biosynthesis* / Q000378:metabolism; D006005:Phosphorylases / Q000378:metabolism; D051381:Rats
D005958:Glucosephosphates; D008112:Liver Glycogen; D019298:Glucose-6-Phosphate; D006005:Phosphorylases; D006006:Glycogen Synthase; D005947:Glucose