Glycogen synthase inhibition

Promotes glucose storage as glycogen (induces glucokinase and glycogen synthase, inhibits phosphorylase)... 

Not only is phosphorylase activated by a rise in concentration of cAMP (via phosphorylase kinase), but glycogen synthase is at the same time converted to the inactive form both effects are mediated via cAMP-dependent protein kinase. Thus, inhibition of glycogenolysis enhances net glycogenesis, and inhibition of glycogenesis enhances net glycogenolysis. Furthermore,... 

Chen G, Jiang Y et al. The mood stabilising agent valproate inhibits the activity of glycogen synthase kinase 3. J Neurochem 1999 72 1327-1330. 

Lithium can selectively inhibit the activity of glycogen synthase kinase-3 6 (GSK-3 ji), an enzyme which regulates cell fate determina-... 

Karelson, Bioorganic and Medicinal Chemistry, 14, 4987 (2006). QSAR Modeling of the Inhibition of Glycogen Synthase Kinase-3. 

Leclerc, S., Garnier, M., Hoessel, R. (2001) et al. Indirubins inhibit glycogen synthase kinase-3 3 and CDK5/P25, two protein kinases involved in abnormal tau phosphorylation in Alzheimer s disease. A property common to most cyclin-dependent kinase inhibitors. J. Biol. Chem., 276, 251-260. 

Figure 6.19 Regulation of the synthesis of glycogen from glucose in liver and muscle. Insulin is the major factor stimulating glycogen synthesis in muscle it increases glucose transport into the muscle and the activity of glycogen synthase, activity which is also activated by glucose 6-phosphate but inhibited by glycogen. The latter represents a feedback mechanism and the former a feedforward. The mechanism by which glycogen inhibits the activity is not known. The mechanism for the insulin effect is discussed in Chapter 12.

The glucose concentration is the major factor regulating glycogen synthesis in liver. Glucose activates glucokinase directly as a substrate and indirectly via an increase in the concentration of fructose 6-phosphate. It also activates glycogen synthase but it inhibits glycogen phosphorylase (see text). 

In addition to inhibition of glycogenolysis, glucose also activates glycogen synthase and hence stimulates glycogen synthesis and this is achieved by an even more intriguing... 

In contrast to glucagon, the peptide hormone insulin (see p. 76) increases glycogen synthesis and inhibits glycogen breakdown. Via several intermediates, it inhibits protein kinase GSK-3 (bottom right for details, see p. 388) and thereby prevents inactivation of glycogen synthase. In addition, insulin reduces the cAMP level by activating cAMP phosphodiesterase (PDE). 

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