Glycogen synthesis regulation

Regulation of glycogen synthesis and degradation is essentially the same in the liver and muscle, but there are a couple of wrinkles. Glycogen degradation is also activated in muscle in response to the rise in intracellular calcium levels that accompanies contraction. This is achieved by... 

Figure 4.23 Regulation of glycogen synthesis. AKT inactivates GSK-3 and so relieves the inhibition...

Glycogen synthesis is important in two tissues, muscle and liver. In muscle the major factors regulating the rate of synthesis are insulin and the amount of glycogen already present in the muscle. In liver, the major factor is the intracellular concentration of glucose (see below) (Figure 6.19). 

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). 

One is the glucose that is absorbed from the intestine and enters the blood in the hepatic portal vein from where some of it is taken np by the Uver and phosphorylated to form glncose 6-phosphate, which then stimulates the formation of glycogen (for discnssion of regulation of this process, see below). This is known as the direct pathway for glycogen synthesis. 

Integration of regulation of glycogen synthesis and glycogen breakdown by glucose... 

Glycogen stores are regulated by a balance between glycogen synthesis (glycogenesis) and breakdown (glycogenolysis). 

The final step in signal transduction is the action of cAMP on the regulatory subunit of the enzyme, protein kinase A. This ubiquitous enzyme then phosphorylates and activates enzymes with functions specific to different cells and organs. In fat cells, protein kinase A activates lipase, which mobilizes fatty acids in muscle and liver cells, it regulates glycogenolysis and glycogen synthesis. 

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.

SUMMARY 15.4 Coordinated Regulation of Glycogen Synthesis and Breakdown... 

Radziuk, J. Pye, S. (2001) Hepatic glucose uptake, gluconeogenesis and the regulation of glycogen synthesis. 

Shulinan, R.G., Block, G., Rothman, D.L. (1995) In vivo regulation of muscle glycogen synthase and the control of glycogen synthesis. Proc. Natl. Acad. Sci. USA 92, 8535-8542. 

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