Glycogenolysis during Tetanic Contraction of Isolated Mouse Muscles in the Presence and Absence of Phosphorylase A.

Muscle contraction may increase the rate of glycogen degradation to several hundred times that present at rest (1, 2). The increase in the rate of conversion of glycogen to lactate in isolated frog sartorius performing single twitches requires changes in the activity of at least two enzymes, glycogen phosphorylase and phosphofructokinase (2). The activation of phosphorylase and control of rapid glycolytic rates in mouse caudofemoralis muscle during tetanic cont,raction is described in the present paper. Glycogen phosphorylase in muscle exists in two forms, phosphorylase b which is catalytically inert unless activated by 5’adenosine phosphate and phosphorylase a which is active in the absence of 5’-adenosine phosphate (3, 4). Phosphorylase a is formed from phosphorylase 6 by a specific kinase (5). In this reaction two serine residues of phosphorylase b are phosphorylated by adenosine triphosphate and the molecule dimerizes (6, 7). In the reverse reaction, phosphate is removed from the serine residue by a specific phosphatase to yield phosphorylase b (8, 9). In isolated frog sartorius muscle phosphorylase is present almost entirely in the b form during rest. With the onset of tetanic contraction at 30”, phosphorylase a increases rapidly (half-time 0.7 second) until it reaches 947, of the total (phosphorylase a and 6 combined) (10). In intact muscle an increase in phosphorylase activity might result from either the activation of phosphorylase b by 5’-adenosine phosphate or the enzymic conversion of phosphorylase b to phosphorylase a. The physiologic role of these two alternatives has been difficult to assess since it has not hitherto been possible to study the effect of muscle work separately from the appearance of phosphorylase a. Such an investigation has been made possible by the discovery that phosphorylase in skeletal muscle of strain I mice is always in the b form (11, 12), presumably as the result of the absence of skeletal muscle phosphorylase b kinase (12). It is shown in the present study that phosphorylase b