Regulation of glycogen metabolism

REGULATION OF GLYCOGEN METABOLISM IS EFFECTED BY A BALANCE IN ACTIVITIES BETWEEN GLYCOGEN SYNTHASE PHOSPHORYLASE (Figure 18-8)... 

The current state of Ser/Thr phosphorylation of a protein is determined by the relative activity of Ser/Thr-specific protein kinase and protein phosphatase. It is therefore imderstandable that the cell has had to develop special mechanisms to balance the two activities with one another, and, when needed, to allow kinase or phosphatase activity to dominate. One of the best investigated examples of coordinated activity of protein kinases and protein phosphatases is the regulation of glycogen metabolism in skeletal muscle. Glycogen metabolism is an example of how two different signals, namely a cAMP signal and a Ca signal meet in one metabolic pathway and control the activity of one and the same enzyme. 

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.

Antoniw, J. F., Nimmo, H. G., teaman, S. J., and Cohen, P. (1977). Comparison of the Substrate Specificities of Protein Phosphatases Involved in the Regulation of Glycogen Metabolism in Rabbit Skeletal Muscle. Biochem J 162 423. 

Protein phosphatase-1 (Mg +/ATP-dependent phosphatase multisubstrate protein phosphatase M.W. of catalytic subunit is 35,000 major enzyme in regulation of glycogen metabolism in skeletal muscle dephosphorylates glycogen phosphorylase, jS-subunit of phosphorylase kinase, and at least three sites of glycogen synthase regulated by inhibitor-1, inhibitor-2, and GSK-3 -t- Mg +- ATP). 

Possible mechanism for regulation of glycogen metabolism in skeletal muscle by changes in cytosolic calcium. Increased glycogen breakdown may be coordinated with muscle contractions, as indicated here. The actual control scheme is probably more complicated, since phosphoprotein phosphatases are also involved. Interactions with cAMP-activated reactions, which also may complicate regulation, are not included. 

Figures 15-11 and 15-12 provide a model for the regulation of glycogen metabolism in muscle. This model is consistent with many of the known facts, but alternative interpretations are equally plausible. Only two of the external stimuli that affect muscle glycogen metabolism are considered in these figures.

Chart 4 Regulation of glycogen metabolism in mammalian liver. 

Gomez-Foix AM, Coats WS, Baque S, et al. Adenovirus-mediated transfer of the muscle glycogen phosphorylase gene into hepatocytes confers altered regulation of glycogen metabolism./ Biol Chem 1992 267 25129-25134. 

A FIGURE 13-17 Regulation of glycogen metabolism by cAMP in liver and muscle cells. Active enzymes are... 

Serotonin appears to be an important regulator of glycogen metabolism in most parasitic helminths. In flatworms, such as Fasciota hepatica or Schistosoma mansoni, serotonin stimulates both glycogen breakdown and muscle contraction in nematodes, such as A. suum, only glycogen breakdown is affected. In F. hepatica, the serotonin... 

Donahue, M. J., Masaracchia, R. A. and Harris, B. G. (1983) The role of cyclic AMP-mediated regulation of glycogen metabolism in levamisole-perfused Ascaris suum muscle. Mol. Pharmacol. 23 378-383. 

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