Hepatic glycogen synthase (regulation)

The regulation of hepatic glycogen synthase should be considered in terms of structure and function:

• the enzyme exists in 2 forms:
  • glycogen synthase a (GSa) is the active form that is non-phosphorylated
  • glycogen synthase b (GSb) is the inactive form that is phosphorylated
• a protein phosphorylase kinase:
  • phosphorylates GSa to GSb
  • increases activity in response to increased cyclic AMP concentration
  • increases activity in response to increased intracellular calcium
• a protein phosphatase:
  • dephosphorylates GSb to GSa
  • is inhibited by high concentrations of glycogen phosphorylase a

Hence, glycogen synthase is stimulated by agents which lower cAMP concentration e.g. insulin, and inhibited by agents which raise cAMP levels e.g. glucagon, adrenaline.

Equally, an increased proportion of the enzyme glycogen phosphorylase in the active a form, as occurs in the presence of reduced cellular glucose concentration, reduces the activity of glycogen synthase.