The inhibitory effect of phosphorylase a on the activation of glycogen synthase depends on the type of synthase phosphatase.
The activity of glycogen synthase phosphatase in rat liver stems from the co-operation of two proteins, a cytosolic S-component and a glycogen-bound G-component. It is shown that both components possess synthase phosphatase activity. The G-component was partially purified from the enzyme-glycogen complex. Dissociative treatments, which increase the activity of phosphorylase phosphatase manyfold, substantially decrease the synthase phosphatase activity of the purified G-component. The specific inhibition of glycogen synthase phosphatase by phosphorylase a, originally observed in crude liver extracts, was investigated with purified liver synthase b and purified phosphorylase a. Synthase phosphatase is strongly inhibited, whether present in a dilute liver extract, in an isolated enzyme-glycogen complex, or as G-component purified therefrom. In contrast, the cytosolic S-component is insensitive to phosphorylase a. The activation of glycogen synthase in crude extracts of skeletal muscle is not affected by phosphorylase a from muscle or liver. Consequently we have studied the dephosphorylation of purified muscle glycogen synthase, previously phosphorylated with any of three protein kinases. Phosphorylase a strongly inhibits the dephosphorylation by the hepatic G-component, but not by the hepatic S-component or by a muscle extract. These observations show that the inhibitory effect of phosphorylase a on the activation of glycogen synthase depends on the type of synthase phosphatase.
D000818:Animals; D002852:Chromatography, Ion Exchange; D004789:Enzyme Activation / Q000187:drug effects; D019298:Glucose-6-Phosphate; D005958:Glucosephosphates / Q000494:pharmacology; D006006:Glycogen Synthase / Q000037:antagonists & inhibitors* / Q000302:isolation & purification; D006007:Glycogen-Synthase-D Phosphatase / Q000378:metabolism*; D066298:In Vitro Techniques; D008099:Liver / Q000201:enzymology; D008297:Male; D009132:Muscles / Q000201:enzymology; D010749:Phosphoprotein Phosphatases / Q000378:metabolism*; D010762:Phosphorylase a / Q000494:pharmacology*; D006005:Phosphorylases / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
D005958:Glucosephosphates; D019298:Glucose-6-Phosphate; D010762:Phosphorylase a; D006005:Phosphorylases; D006006:Glycogen Synthase; D010749:Phosphoprotein Phosphatases; D006007:Glycogen-Synthase-D Phosphatase