Glycogen as a fuel for skeletal muscle.

The utilization of glycogen by skeletal muscle was, at one time, one of the central problems of biochemistry. Attention focused on the most dramatic property of the system: the very rapid glycogenolysis that occurs synchronously with muscle contraction. This phenomenon now has a generally accepted explanation : the increase in Ca2+ that induces muscle contraction also activates phosphorylase kinase. This enzyme catalyses the phosphorylation of inactive phosphorylase b to active phosphorylase a and this, finally, catalyses glycogenolysis. Another mechanism whereby an extrinsic stimulus catalyses glycogenolysis is also well understood. Circulating hormones indirectly activate cyclic AMP-dependent protein kinase, which catalyses phosphorylation of phosphorylase kinase to a more active form, which functions at lower Caz+ concentration. Graves & Wang (1972) have reviewed these pathways. Another mechanism has been extensively studied in uitro with purified phosphorylase, but is less well understood in viuo. This involves non-covalent activation of phosphorylase b by binding of A M P or IMP. Both thesc activators accumulate in energydepleted tissues, whereas two inhibitory nucleotides, ATP and ADP, predominate in energy-rich tissues. Glucose 6-phosphate, the enzyme’s effective product, is also a potent inhibitor, and somewhat less effective inhibition is provided by UDP-glucose, the substrate for glycogen synthesis. This system, shown in Scheme I , would provide a mechanism wherebya constant concentration of glucose 6-phosphate may be maintained in skeletal muscle by glycogenolysis to supply the metabolic needs of the muscle cell.