Glycogen metabolism degradation

C. As glucose is consumed by cellular metabolism, glycogen is degraded (glycogenolysis) to form free glucose in an effort to maintain relatively constant blood glucose levels. 

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.

Renewed docking of the catalytic subunit requires the removal of the phosphate residue at the G subunit phosphorylated at the P2 site. This takes place via the protein phosphatases 2A and 2B (calcineurin). Thus, a cascade of protein phosphatases is involved in the regulation of dephosphorylation of key enzymes of glycogen degradation, whereby a phosphatase, namely protein phosphatase I, is indirectly activated by other protein phosphatases. With calcineurin, a Ca -dependent protein phosphatase is involved and thus it is possible to influence glycogen metabolism via Ca -mediated signals. 

As we have seen in glycolysis and gluconeogenesis, biosynthetic and degradative pathways rarely operate by precisely the same reactions in the forward and reverse directions. Glycogen metabolism provided the first known example of this important principle. Separate pathways afford much greater flexibility, both in energetics and in control. 

Glycogen degradation is stimulated and synthesis is inhibited when the enzymes of glycogen metabolism are phosphorylated. 

Glycogen metabolism is important for the proper function of many aspects of cellular metabolism. Many diseases of glycogen metabolism have been discovered. Generally, these are diseases that result in the excessive accumulation of glycogen in the liver, muscle, and tubules of the kidneys. Often they are caused by defects in one of the enzymes involved in the degradation of glycogen. 

Defects in other enzymes of glycogen metabolism also exist. Cori s disease is caused by a genetic defect in the debranching enzyme. As a result, individuals who have this disease cannot completely degrade glycogen and thus use their glycogen stores very inefficiently. 

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