TIME-DEPENDENT PSEUDO-ACTIVATION OF HEPATIC GLYCOGEN-SYNTHASE-B BY GLUCOSE-6-PHOSPHATE WITHOUT INVOLVEMENT OF PROTEIN PHOSPHATASES

During a 30 min incubation at 25 degrees C in the presence of 5-10 mM glucose B-phosphate, pure glycogen-bound glycogen synthase b from dog liver was progressively converted into a form that was fully catalytic ally active in the presence of 10 mM Na2SD4 plus 0.5 mM glucose 6-phos phate, The latter enzyme was unlike synthase a (which does not require glucose 6-phosphate for activity), and unlike synthase b (which is st rongly inhibited by sulphate), The conversion was insensitive to vario us inhibitors of Ser/Thr-protein phosphatases and alkaline phosphatase s, and was therefore termed 'pseudo-activation'. Kinetically, pseudo-a ctivation increased the V-max 4-fold without affecting the K-m for the substrate UDP-glucose. Pseudo-activation appeared to be an irreversib le process, but several lines of evidence argue against a limited prot eolysis. Pseudo-activation of glycogen synthase occurred also readily in a rat liver cytosol, but it was not observed with purified synthase from skeletal muscle. These observations have important implications for the assay of liver glycogen-synthase phosphatase; the possible phy siological implications remain to be explored.