Role of cyclic AMP and inorganic phosphate in the regulation of muscle glycogenolysis during exercise.

The roles of cAMP and inorganic phosphate (Pi) in the regulation of muscle glycogenolysis during exercise have been investigated in humans using the needle biopsy technique. The fraction of phosphorylase a in resting muscle was as a mean 23%, but the rate of glycogenolysis was extremely low. Epinephrine infusion increased cAMP in muscle by 3-fold and transformed 80% of phosphorylase to the a form. Despite this, the rate of glycogenolysis was only 5-10% of the maximum rate of phosphorylase a (Vmax a) determined in vitro. Isometric exercise for 25 s at 66% MVC or electrical stimulation for 50 s at 20 Hz transformed about 53% and 80% of phosphorylase in the a form. The rate of glycogenolysis ranged between 50-90 mmol.kg-1.dm.min-1 and was close to Vmax of phosphorylase a determined in vitro. No significant difference in the rate of glycogenolysis in muscle was observed after isometric exercise to fatigue without and with epinephrine infusion, respectively. Apparently the rate of glycogenolysis in muscle is not solely related to the fraction of phosphorylase in the a form. Several factors could be responsible for allosteric and/or substrate regulation. The results in the present studies can be explained on the basis of substrate regulation of phosphorylase activity, provided that Pi is present in a limiting amount at the active site of phosphorylase in muscle at rest. It is concluded that transformation of phosphorylase b to a is important but alone is not adequate for a high activity and thus for a high rate of glycogenolysis in muscle.(ABSTRACT TRUNCATED AT 250 WORDS)