Glycogen synthase D, like the other form of the enzyme (glycogen synthase I), catalyzes the addition of a glucose molecule (from UDP-glucose) in an 1,4 linkage to a growing glycogen chain. The two enzymes are identical except that glycogen synthase D arises from phosphorylation of glycogen synthase I by cAMP-dependent protein kinase or SPK (Figures 16.11 and 16.12). The phosphate group on glycogen synthase D causes it to be dependent on glucose-6-phosphate for activity. In the absence of glucose-6-phosphate, glycogen synthase is inactive.

cAMP-dependent protein kinase can phosphorylate glycogen synthase I directly, or it can phosphorylate SPK (also known as phosphorylase b kinase), which in turn is activated to phosphorylate glycogen synthase I. Phosphorylation converts glycogen synthase I to glycogen synthase D.

Conversion of the D form back to the I form requires action of the enzyme phosphoprotein phosphatase I.Glycogen synthase I is called the independent form of glycogen synthase, since it does not require glucose-6-phosphate for activity.

cAMP-dependent protein kinase requires cAMP for activity. Therefore, hormones, such as epinephrine and glucagon, which increase cAMP levels, tend to inactivate synthesis of glycogen due to conversion of glycogen synthase I to the dependent form (glycogen synthase D).

Conversely, hormones, such as insulin, which reduce cAMP levels and counteract the effects of cAMP-dependent protein kinase activity, stimulate dephosphorylation of glycogen synthase D by the enzyme phosphoprotein phosphatase I to the independent form (I) and favor glycogen synthesis.