Glycogen synthase control

The principal enzymes controlling glycogen metabolism—glycogen phosphorylase and glycogen synthase— are regulated by allosteric mechanisms and covalent modifications due to reversible phosphorylation and... 

Figure 18-7. Control of glycogen synthase in muscle (n = number of glucose residues). The sequence of reactions arranged in a cascade causes amplification at each step, allowing only nanomole quantities of hormone to cause major changes in glycogen concentration. (GSK, glycogen synthase kinase-3, -4, and -5 G6P, glucose 6-phosphate.)...

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. 

The key control enzyme in the pathway is glycogen synthase (GS) which occurs in either a high activity state (GS-a) or a low activity state (GS-b) the switch from one to the other is brought about partly by covalent modification of the enzyme in response to stimulation by glucagon and partly by allosteric effects of key metabolites. Glycogen... 

Glycogen synthase kinase-3 is itself subject to control by reversible phosphorylation. Stimulation of the liver cell by insulin, the key hormone of the postprandial state,... 

As indicated in Section 6.3.3 and Table 6.2 the key control step is mediated by glycogen phosphorylase, a homodimeric enzyme which requires vitamin B6 (pyridoxal phosphate) for maximum activity, and like glycogen synthase (Section 6.2) is subject to both allosteric modulation and covalent modification. 

Figure 6.40 Reciprocal control of glycogen phosphorylase and glycogen synthase...

Glycogen synthase forms the O -1,4 glycosidic bond found in the linear glucose chains of the granule. Table 1-14-1 shows the control of glycogen synthase in liver and skeletal muscle. 

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. 

Table 4.6.20 Control and pathological values (U/g) for glycogen synthase assay...

FIGURE 15-36 Control of glycogen synthesis from blood glucose in myocytes. Insulin affects three of the five steps in this pathway, but it is the effects on transport and hexokinase activity, not the change in glycogen synthase activity, that increase the flux toward glycogen. 

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. 

IntraeeUulat Controls phosphorylase Glycogen synthase Phosphofrm tokinase phosphatase -... 

Breum L, Bjerre U, Bak JF, Jacobsen S, Astrup A (1995) Long-term effects of fluoxetine on glycemic control in obese patients with non-insulin-dependent diabetes mellitus or glucose intolerance influence on muscle glycogen synthase and insulin receptor kinase activity. Metabolism 44 1570-1576... 

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