Glycogen synthase dephosphorylation

Glycogen synthase also exists in two distinct forms which can be interconverted by the action of specific enzymes active, dephosphorylated glycogen synthase I (glucose-6-P-independent) and less active phosphorylated glycogen synthase D (glucose-6-P-dependent). The nature of phosphorylation is more complex with glycogen synthase. As many as nine serine residues on the enzyme appear to be subject to phosphorylation, each site s phosphorylation having some effect on enzyme activity. 

Dephosphorylation of both glycogen phosphorylase and glycogen synthase is carried out by phosphoprotein phosphatase 1. The action of phosphopro-tein phosphatase 1 inactivates glycogen phosphorylase and activates glycogen synthase. 

Like phosphorylase, glycogen synthase exists in either a phosphorylated or nonphosphorylated state. However, unlike phosphorylase, the active form is dephosphorylated (glycogen synthase a) and may be inactivated to... 

Welsh, G. I., Miller, C. M Loughlin, A. J., Price, N. T., and Proud, C. G. (1998). Regulation of eukaryotic initiation factor eIF2B Glycogen synthase kinase-3 phosphor-ylates a conserved serine which undergoes dephosphorylation in response to insulin. FEBS Lett. 421, 125-130. 

Synthesis of glycogen from UDP-glucose is catalyzed by glycogen synthase, which is rate-controlling. As in other tissues, glycogen synthase occurs in both a phosphory-lated form, synthase-b, which depends on Glc-6-P as a positive modulator, and a dephosphorylated, independent synthase-a form, which is much more active. 

In the fed state when the insulin glucagon ratio is high, would you expect glycogen synthase, PK and PDH to be phosphorylated or dephosphorylated Give reasons to support your answer. 

Since the enzyme glycogen synthase catalyses the rate-limiting step in glycogen synthesis, it is the activity of this enzyme that must be increased as the blood glucose concentration increases. This is achieved via an interconversion cycle (i.e. reversible phosphorylation). A protein kinase phosphorylates it, which inactivates the enzyme, whereas a protein phosphatase dephosphorylates it, which... 

Glycogen synthase is regulated via the same pathway. Glycogen synthase is inactive in the phosphorylated form whereas in the dephosphorylated form, it is active. Three key enzymes of glycogen metabohsm are thus controlled with the help of reversible protein phosphorylation. 

Fig. 7.21. Activation of glycogen-bound protein phosphatase I by insulin. Insulin has a stimulating effect on glycogen synthesis by initiating the dephosphorylation and activation of glycogen synthase and the dephosphorylation and inhibition of glycogen phosphorylase. Both enzymes (substrate S in the figure) are dephosphorylated by protein phosphatase PPIG. Insulin mediates the activation of a protein kinase (insulin-sensitive protein kinase) within an insulin-stimulated signal pathway, which phosphorylates and thus activates protein phosphatase PPIG at the PI site.

Fig. 12-23). Glycogen synthase kinase 3 (GSK3) is inactive when phosphorylated on a Ser residue in its auto-inhibitory domain (Fig. 12-23b). Dephosphorylation of that domain frees the enzyme to bind and phosphory-late its target proteins. Similarly, the polar head group of the phospholipid PIP3, protruding from the inner leaflet of the plasma membrane, provides points of attachment for proteins that contain SH3 and other domains. 

Glycogen Synthase Is Also Regulated by Phosphorylation and Dephosphorylation... 

Glycogen synthase a is inactivated by phosphorylation catalyzed by GSK3. Insulin blocks GSK3. PP1, which is activated by insulin, reverses the inhibition by dephosphorylating glycogen synthase b. 

Glycogen synthase (muscle) Enzymes of lipid synthesis Dephosphorylation... 

The dephosphorylated form of the carboxylase does not require citrate for activity, but the phosphorylated form of the enzyme can be activated by citrate in vitro. This reaction is reminiscent of the effect of glucose-6-phosphate on glycogen synthase. The active, dephosphorylated form of glycogen synthase has only a small requirement for glucose-6-phosphate, whereas high concentrations of this activator are required to activate the phosphorylated form of glycogen synthase. 

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