Phosphatases glycogen synthesis

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... 

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.

The glucocorticoids have important dose-related effects on carbohydrate, protein, and fat metabolism. The same effects are responsible for some of the serious adverse effects associated with their use in therapeutic doses. Glucocorticoids stimulate and are required for gluconeogenesis and glycogen synthesis in the fasting state. They stimulate phosphoenolpyruvate carboxykinase, glucose-6-phosphatase, and glycogen synthase and the release of amino acids in the course of muscle catabolism. 

Diabetes - insulin dependent Methyl malonic, propionic or isovaleric acidaemias Pyruvate carboxylase and multiple carboxylase deficiency Gluconeogenesis enzyme deficiency glucose-6-phosphatase, fructose-1,6-diphosphatase or abnormality of glycogen synthesis (glycogen synthase) Ketolysis defects Succinyl coenzyme A 3-keto acid transferase ACAC coenzyme A thiolase... 

Semiz, S. and J.H. McNeill. 2002. Oral treatment with vanadium of Zucker fatty rats activates muscle glycogen synthesis and insulin-stimulated protein phosphatase-1 activity. Mol. Cell. Biochem. 236 123-131. 

Insulin could also promote glycogen synthesis by activating glycogen synthase phosphatase, rather than inactivating glycogen synthase kinase. However, a pathway linking insulin receptor activation to the activation of serine/threonine phosphatases of the PPl type has not yet been identified. 

Insulin Stimulates Glycogen Synthesis by Activating Protein Phosphatase 1... 

Figure 21.20. Insulin Activates Protein Phosphatase 1. Insulin triggers a cascade leading to the activation of protein phosphatase 1, which results in the stimulation of glycogen synthesis and inhibition of its breakdovm. The activated receptor tyrosine kinase switches on a putative master kinase that phosphorylates the insulin-sensitive protein kinase. In turn, the glycogen-targeting suhunit (Rgj suhunit) of the phosphatase is phosphorylated, which activates the enzyme. [After P. Dent, A. Lavoirme, S. Nakielny, F. B. Caudwell, P. Watt, and P. Cohen. Nature 348(1990) 306.]...

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