Glycogen metabolism synthesis

H, receptors in brain slices can also stimulate glycogen metabolism [5] and can positively modulate receptor-linked stimulation of cAMP synthesis. The activation of brain cAMP synthesis by histamine is a well studied phenomenon that reveals a positive interaction between histamine receptors [35]. When studied in cell-free preparations, this response shows characteristics of H2, but not H receptors. When similar experiments are performed in brain slices, however, both receptors appear to participate in the response. Subsequent work showed that H receptors do not directly stimulate adenylyl cyclase but enhance the H2 stimulation, probably through the effects of calcium and PKC activation on sensitive adenylyl cyclase iso forms (see Ch. 21). 

Glycogen and its enzymes are compartmentalized. Glycogen granules are only present in astrocytes of adult animals but are found in both astrocytes and neurons of immature animals. Of the enzymes involved in glycogen metabolism, glycogen phosphorylase is found in astrocytes only. Under steady-state conditions, it is probable that less than 10% of phosphorylase in brain is in the unphosphorylated b form (requiring AMP). This form is probably not very active at the low AMP concentrations present when intracellular glucose is sufficient to maintain ATP synthesis. Brain phosphorylase b kinase is activated indirectly by cAMP and by the molar concentrations... 

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.

In glycogen metabolism (Section 21.5). PKA phosphorylates two enzymes that lead to the breakdown of this polymeric store of glucose and the inhibition of further glycogen synthesis. 

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

Figure 25-14 Mechanism of insulin action. Binding of insulin to the extracellular a-subunit of the insulin receptor induces autophosphorylation of the -subunit of the receptor and phosphorylation of selected intracellular proteins, such as She and the IRS family,These latter phosphoproteins interact with other targets, thereby activating phosphorylation cascades, which result in glucose uptake (in adipose tissue and skeletal muscle), glucose metabolism, synthesis (of glycogen, iipid, and proteins), enhanced gene expression, cell growth, and differentiation, p, protein phosphorylation aPKC, atypical protein kinase C, See text for details.

Figure 21.17 Coordinate control of glycogen metabolism. Glycogen metabolism is regulated, in part, by hormone triggered cyclic AMP cascades. The sequence of reactions leading to the activation of protein kinase A ultimately activates glycogen degradalion. At the same time, protein kinase A also inactivates glycogen synthase, shutting down glycogen synthesis.

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