Covalent Inhibition of Glycogenesis

The regulated enzyme in glycogenesis, glycogen synthase, also exists in two forms, the active “a” form and the inactive “b” form. However, in contrast to phosphorylase kinase and phosphorylase, the active form of glycogen synthase is dephosphorylated, whereas the inactive form is phosphorylated at several sites on the enzyme, with the level of inactivation proportional to the degree of phosphorylation (Fig. 1). Phosphorylation is catalyzed by several different protein kinases in response to cAMP (for example, PKA and phosphorylase kinase) or other signaling mechanisms (see C. below). Glycogen synthase b can be reconverted to the “a” form by PP1. Figure 2 summarizes the covalent regulation of glycogen metabolism.

Figure 1: Hormonal regulation of glycogen synthesis. [Note: In contrast to glycogen phosphorylase, glycogen synthase is inactivated by phosphorylation.] cAMP = cyclic adenosine monophosphate; = phosphate; PPi = pyrophosphate; R = regulatory subunit; C = catalytic subunit; ADP = adenosine diphosphate.

Figure 2: Summary of the hormone-mediated covalent regulation of glycogen metabolism. cAMP = cyclic adenosine monophosphate; PKA = protein kinase A.