Muscle Glycogen Synthase

This chapter discusses the structure and activity of muscle glycogen synthase. Glycogen synthase is regulated by a phosphorylation–dephosphorylation mechanism. Following the discovery that glycogen phosphorylase and phosphorylase kinase were activated by phosphorylation, Larner and co-workers found that glycogen synthase could exist in two forms in mammalian skeletal muscle. One possessed little activity without glucose 6-phosphate (G6P), whereas the other was almost fully active in the absence of this allosteric activator. The conversion of glycogen synthase from a G6P-independent to a G6P-dependent form is shown to require MgATP and a further protein and to be stimulated by cyclic adenosine 3′,5′-monophosphate (cAMP). The basis for these effects became clearer following the purification of glycogen synthase to homogeneity, when the enzyme is phosphorylated by cAMP-dependent protein kinase. It was reported in an earlier study that the G6P-dependent form contained ≃6 mol phosphate/86 kDa subunit, and with the subsequent identification of additional glycogen synthase kinases it became clear that glycogen synthase is regulated by multisite phosphorylation.