Kinase Cascade

Glycogen metabolism (and other metabolic pathways, as well) is regulated by phosphorylation and dephosphorylation of a set of proteins. These are depicted in Figure 13.18, Figure 16.11, and Figure 16.12. The reactions in the phosphorylation occur in a cascading mechanism, referred to here as a kinase cascade. It operates as follows in the cell:

> 1. Stimulus for phosphorylation is hormone interaction (glucagon or epinephrine) with a cellular receptor, which sends a signal via a G protein to the membrane-bound enzyme, adenylate cyclase.

> 2. Adenylate cyclase, in turn, forms cAMP from ATP.

> 3. cAMP activates cAMP-dependent protein kinase.

> 4. cAMP-dependent protein kinase phosphorylates phosphorylase b kinase.

> 5. Phosphorylase b kinase phosphorylates glycogen phosphorylase b to convert it to glycogen phosphorylase a.

> 6. Glycogen phosphorylase a catalyzes phosphorolysis of glycogen to form glucose-1-phosphate.

Phosphorylation of proteins in glycogen metabolism favors glycogen breakdown, inhibits glycogen synthesis

Coincident with stimulating glycogen breakdown, cAMP exerts two effects in inhibiting glycogen synthesis:

> 1. Phosphorylation of glycogen synthase, converting it to a form dependent on glucose-6-phosphate.

> 2. Inhibition of phosphoprotein phosphatase (PP-1), whose activity would tend to restore activity of glycogen synthase. PP-1 and other phosphoprotein phosphatases play converse roles in glycogenolysis, in which dephosphorylation of glycogen phosphorylase b kinase (SPK) causes its inactivation.

See also: Calmodulin, Mechanism of Activating Glycogen Breakdown, Glycogen Breakdown Regulation, Glycogen Breakdown, Kinase Cascade in Fat Mobilization (from Chapter 18), Second Messenger Systems