Ch2

FIGURE 15-26 Glycogen phosphorylase of liver as a glucose sensor.

Glucose binding to an allosteric site of the phosphorylase a isozyme of liver induces a conformational change that exposes its phosphory-lated Ser residues to the action of phosphorylase a phosphatase 1(PP1).

This phosphatase converts phosphorylase a to phosphorylase b, sharply reducing the activity of phosphorylase and slowing glycogen breakdown in response to high blood glucose. Insulin also acts indirectly to stimulate PP1 and slow glycogen breakdown.

FIGURE 15-27 Effects of GSK3 on glycogen synthase activity.

Glycogen synthase a, the active form, has three Ser residues near its carboxyl terminus, which are phosphorylated by glycogen synthase kinase 3 (GSK3). This converts glycogen synthase to the inactive (b) form (GSb). GSK3 action requires prior phosphorylation (priming) by casein kinase (CKII). Insulin triggers activation of glycogen synthase b by blocking the activity of GSK3 (see the pathway for this action in Fig. 12-8) and activating a phosphoprotein phosphatase (PP1 in muscle, another phosphatase in liver). In muscle, epinephrine activates PKA, which phosphorylates the glycogen-targeting protein Gm (see Fig. 15-30) on a site that causes dissociation of PP1 from glycogen. Glucose 6-phosphate favors dephosphorylation of glycogen synthase by binding to it and promoting a conformation that is a good substrate for PP1. Glucose also promotes dephosphorylation; the binding of glucose to glycogen phosphorylase a forces a conformational change that favors dephosphorylation to glycogen phosphorylase b, thus relieving its inhibition of PP1 (see Fig. 15-29).

Phosphoserines near carboxyl terminus

Phosphoserines near carboxyl terminus

Insulin

Glucagon, epinephrine

Glucose 6-phosphate

Glucose

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