Regulation of Glycogenolysis in Muscle

Conversion of glycogen to hexose monophosphate in muscle appears to be limited by the activity of phosphorylase (l-3). The enzyme exists in two forms, a and b. Increased phosphorylase activity can result from (a) conversion of phosphorylase b to a (l-5), and (6) regulation of phosphorylase b activity by changes in the intracellular levels of adenine nucleotides (6). In the isolated rat heart perfused with aerobic buffer, intracellular adenosine monophosphate (AMP) concentrations appeared to be well above the K, value for AMP activation of phosphorylase b (3, 6). The rate of glycogenolysis indicated, however, that phosphorylase was inactive. An explanation for these findings appeared to be that adenosine triphosphate (ATP), which was present in high concentration in aerobic muscle, inhibited the activation of phosphorylase b by AMP. In the present study we have assayed the activities of crystalline phosphorylases a and b from skeletal muscle under conditions simulating those occurring in aerobic and anoxic heart muscle (3). Addition of “aerobic” and “anaerobic” concentrations of adenine nucleotides, hexose monophosphate, and inorganic orthophosphate produced changes in activity that could account for the changes in glycogenolysis found in the heart perfused under aerobic and anaerobic conditions. It is proposed that physiological regulation of glycogenolysis occurs not only by conversion of phosphorylase b to a, but also by regulation of the activity of phosphorylase b through changes in concentrations of glucose 6-phosphate, AMP, and ATP.