Regulation of Hepatic Glycogen Synthetase of Rana catesbeiana: STUDIES OF ADENOSINE TRIPHOSPHATE INHIBITION WITH REFERENCE TO INSULIN ACTIVATION OF GLYCOGEN SYNTHETASE

Abstract

Abstract Treatment of Rana catesbeiana tadpoles with insulin results in activation of glycogen synthetase. Glycogen synthetase from insulin-treated animals has a lower Km for uridine diphosphoglucose and the nature of ATP inhibition is changed from cooperative to strictly competitive with substrate and with the activator, glucose 6-phosphate. A change in the mechanism of ATP inhibition from cooperative to strictly competitive with substrate and activator is also obtained by photo-oxidation of the untreated enzyme. Other properties of the insulin-activated and photo-oxidized enzymes are also similar: (a) cooperativity for glucose-6-P and UDP-glucose in the presence of ATP is no longer observed; (b) inhibition by ATP is more completely reversed by glucose-6-P in these enzymes compared with untreated glycogen synthetase. It is proposed that in the untreated enzyme ATP interacts with an allosteric regulatory site in addition to the UDP-glucose and glucose-6-P sites. Treatment with insulin in vivo or photo-oxidation in vitro abolishes the functional allosteric regulatory site for ATP without affecting the other ATP sites. It is not yet clear whether the insulin-mediated enzyme modification that results in a reduced Km for UDP-glucose is separate from that which inactivates the allosteric regulatory site for ATP.