Glycogen Synthetase Activity in Skeletal Muscle. Interconversion of Two Forms and Control of Glycogen Synthesis.

Glycogen synthetase (uridine diphosphate glucose-glycogen glucosyltransferase, EC 2.4.1.11) has been extensively studied in liver and in skeletal muscle (3-8). In extracts from a variety of tissues, measurements of the activity of the enzymes catalyzing the steps from n-glucose 6-phosphate to glycogen suggested that glycogen synthetase was rate-limiting and, hence, was likely to be important in the control of the rate of glycogen synthesis (3, 9). A possible mechanism for control became apparent when it was found that in skeletal muscle from several mammals glycogen synthet.ase exists in two enzymatically interconvertible forms: synthetase I, active in the absence of glucose-6-P, and synthetase D, with full activity in the presence of glucose-6-P, but greatly reduced activity in its absence (5-8). Glucose-6-P does not itself enter the reaction (3). The synthetase I + D reaction requires adenosine triphosphate and Mg+f and involves phosphorylation of the enzyme protein from the terminal phosphate of adenosine triphosphate (10). The synthetase D --+ I reaction is accompanied by release of inorganic phosphate from the protein (10). The present paper describes the interconversion of these two forms of glycogen synthetase in living muscle in response to physiological stimuli. It is shown that the two forms are regulated in such a way as to hasten glycogen synthesis when the tissue concentration of glycogen is low, and to slow glycogen synthesis when the tissue concentration is elevated. In addition, the effects of epinephrine and of insulin on this system are described.