The Interconversion of Liver Glycogen Synthetase a and b in vitro

The activation of liver glycogen synthetase b into a in vitro is greatly accelerated by caffeine and theophylline, and is inhibited by fluoride, EDTA, glycogen, P i and sulfate. The inhibition by fluoride and EDTA is partially released by an excess of magnesium but not by the methyl‐xanthines. This activation is also suppressed when ATP is added to the homogenate or when the concentration of endogenous ATP is maintained at a high level by shaking the preparation in the air. The inactivation of synthetase a into b in vitro can be studied after its previous activation performed either in vitro at 20° or in vivo by treatment of the animals with glucose or with glucocorticoids. The inactivation occurs only in the presence of exogenous or endogenous ATP and is accelerated by 3′,5′‐cyclic AMP. It is inhibited by glucose 6‐phosphate, even in the presence of the cyclic AMP, and by glycogen only in the absence of the nucleotide. A half maximal inactivation is obtained in the presence of 0.2 μM 3′,5′‐AMP. All these findings are in agreement with the hypothesis that the activation of liver glycogen synthetase is catalyzed by a specific phosphatase whereas its inactivation is a phosphorylation at the expense of ATP under the action of a specific kinase.