Glycogen synthase, regulation dephosphorylation

A Closer Look at Glycogen Synthase Regulation Dephosphorylation of the D Form (Figure 16.12)... 

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). 

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. 

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. 

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

Glycogen synthase is also regulated by covalent modification and allosteric interactions. The enzyme exists as an active glycogen synthase a and a normally inactive glycogen synthase b. However, in contrast to phosphorylase, it is the active form of glycogen synthase (synthase a) that is dephosphorylated whereas the inactive synthase b form is the phosphorylated form (Fig. 2b). 

Figure 18.14 Glycogen biosynthesis and degradation regulation. cAMP activates cAMP-dependent protein kinases. They cause the phosphorylation of glycogen synthase (inactivation), phosphorylase kinase (activation), and the inhibitory protein. The last inhibits phosphoprotein phosphatase. Activated phosphorylase kinase causes the phosphorylation of phosphorylase b, thus activating it to phosphorylase a. Phosphoprotein phosphatase is inhibited by the phosphorylated inhibitor protein. Such inhibition is released when the inhibitor protein is dephosphorylated. The phosphatase then reactivates glycogen synthase and inactivates phosphorylase kinase and phosphorylase a.

Dephosphorylation of glycogen synthase and glycogen phosphorylase reverses the effects of phosphorylation. This converts glycogen synthase to the independent form and glycogen phosphorylase to a less active form. The primary enzyme responsible for dephosphorylating the glycogen metabolism enzymes is phosphoprotein phosphatase (PP-1). It is regulated by another protein called phosphoprotein phosphatase inhibitor (PI-1). PI-1 is also phosphorylated by active protein kinase. When phosphorylated, PI-1 inhibits PP-1. 

Fig. 36.2. Regulation of glycogen synthase. This enzyme is phosphorylated by a series of kinases, which are initiated by the cAMP-dependent protein kinase, under fasting conditions. it is dephosphorylated and active after a meal, and glycogen is stored. Circled P = phosphate a circled + sign = activated by a circled — sign = inhibited by.

Fig. 11-11 Regulation of glycogen synthase by phosphorylation, dephosphorylation, and glucose 6-phosphate. Phosphorylation of glycogen synthase takes place via at least seven different protein kinases as indicated. cAMP denotes cyclic AMP. The dashed arrows with adjacent -t and - signs denote activation or inhibition, respectively.

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