skeletal muscle glycogen synthase (regulation)

Last reviewed 01/2018

Unlike liver glycogen synthase, skeletal muscle glycogen synthase exists in at least three interconvertable forms. The forms differ from each other in their degree of phosphorylation. Increased phosphorylation results in decreased activity.

Phosphorylation occurs at different sites on glycogen synthase by 3 enzymes:

• glycogen synthase kinase 1 (GSK1); increases activity in response to cAMP
• GSK2:
• when activated, also acts to phosphorylate the enzyme glycogen phosphorylase; hence, it decreases glycogen synthase activity but increases glycogen phosphorylase activity
• has a binding site for calcium; calcium increases GSK 2 activity, so decreasing the activity of glycogen synthase
• GSK2 exists in at least 2 forms; the active form is phosphorylated; dephosphorylation to the inactive form depends on the presence of a phosphatase
• GSK3; activity increased by elevations in cAMP

Similarly to glycogen phosphorylase, glycogen synthase may also be dephosphorylated by phosphatase enzymes. The phosphatase enzymes may be stimulated by reductions in cAMP concentration.

Hence, glycogen synthase in skeletal muscle may be stimulated by insulin, which acts to reduce cAMP concentration. The reverse is true for adrenaline. Due to an absence of membrane receptors, glucagon does not tend to act on skeletal muscle.

Calcium released during excitation-contraction coupling acts on GSK2 to indirectly reduce glycogen synthase activity.