Hormones glycogen degradation

Fig. 7.18. Regulation of glycogen metabolism in muscle. Phosphorylase kinase stands at the center of regulation of glycogen metabolism. Phosphorylase kinase may exist in an active, phosphorylated form and an inactive, unphosphorylated form. Phosphorylation of phosphorylase kinase is triggered by hormonal signals (e.g. adrenahne) and takes place via an activation of protein kinase A in the cAMP pathway. In the absence of hormonal stimulation, phosphorylase kinase can also be activated by an increase in cytosolic Ca. The active phosphorylase kinase stimulates glycogen degradation and inhibits glycogen synthesis, in that, on the one side, it activates glycogen phosphorylase by phosphorylation, and on the other side, it inactivates glycogen synthase by phosphorylation.

Glycogen degradation and glycogen synthesis are controlled both by allosteric regulation and by hormonal control. 

Figure 21.14. Regulatory Cascade for Glycogen Breakdown. Glycogen degradation is stimulated by hormone binding to 7TM receptors. Hormone binding initiates a G-protein-dependent signal-transduction pathway that results in the phosphorylation and activation of glycogen phosphorylase.

Skeletal muscle cells lack glucagon receptors. Hormonal control of glycogen degradation is achieved by epinephrine via P-adrenergic activation of adenylate cyclase, resulting in enhanced cytoplasmic cyclic AMP levels. Neural activation of skeletal muscle cells considerably increases the cytoplasmic Ca level. Cyclic AMP and Ca " act in a synergistic fashion to fully express the activity of glycogen phosphorylase in the process described above (Devlin, 1992). 

The target proteins affected by cAMP depend on the cell type. In addition, several hormones may activate the same G protein. Therefore different hormones may elicit the same effect. For example, glycogen degradation in liver cells is initiated by both epinephrine and glucagon. 

This elegant system of hormonal control ensures that the reactions involved in glycogen degradation and synthesis do not compete with one another. In this way they provide glucose when the blood level is too low, and they cause the storage of glucose in times of excess. 

Insulin results in the activation of PPl. The hormone activates an insulin-sensitive protein kinase that phosphorylates a subunit of PPl, rendering the phosphatase more active. The activated phosphatase dephosphorylates phosphorylase, protein kinase, and glycogen synthase. These changes result in a decrease in glycogen degradation and the stimulation of glycogen synthesis. 

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