In muscle, phosphorylase b is inactivated by

In muscle, glycogen phosphorylase is activated by hormones and neural signals such as epinephrine, that stimulate phosphorylase kinase which phosphorylates the Ser-14 residue of the protein. A second messenger of a cyclic AMP (cAMP) increases in concentration due to epinephrine or glucagon, and this increase results in an enzyme cascade. Activation of phosphorylase kinase is due to increased concentrations of Ca2+ or by the phosphorylation by protein kinase A which is cAMP-dependent. The activated kinase, in turn, activates the glycogen phosphorylase enzyme by phosphorylating the Ser-14 residue. In the liver, glucagon is the primary signal which catalyzes this enzyme cascade. Glycogen phosphorylase b is not always inactive in muscle, as it can be activated allosterically by AMP. An increase in AMP concentration, which occurs during strenuous exercise, signals energy demand. AMP activates glycogen phosphorylase b by changing its conformation from a tense to a relaxed form. This relaxed form has similar enzymatic propeies as the phosphorylated enzyme. An increase in ATP concentration opposes this activation by displacing AMP from the nucleotide binding site, indicating sufficient energy stores.