Glycogen synthase activation

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.

FIGURE 15-27 Effects of GSK3 on glycogen synthase activity. 

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. 

Correct answer = B. Epinephrine and glucagon both cause increased glycogen degradation in the liver. Therefore, glycogen phosphorylase activity is increased, whereas glycogen synthase activity is decreased. Both cAMP-dependent protein kinase and its substrate, phosphorylase kinase, are also activated. 

Fig. 2. Regulation of (a) glycogen phosphorylase activity and (b) glycogen synthase activity by phosphorylation (covalent modification).

Starch synthase or glycogen synthase activity can be measured by transfer of [14C]glucose from ADPGlc into an appropriate primer, such as amylopectin or rabbit glycogen, followed by precipitation of the labeled polymer.171172... 

Lawrence, J. C., and Roach, P. J. (1997). New insights into the role and mechanisms of glycogen synthase activation by insulin. Diabetes 46,541-547. 

Dwek, R.A., and Redman, C.W. Preeclampsia is associated with an increase in trophoblast glycogen content and glycogen synthase activity, similar to that found in hydatidiform moles. J. Clin. Invest., 1993, 91, 2744-2753. 

Figure 20-2. The mobilization of glycogen in the liver in response to hormonal signals. Binding of the hormones glucagon and/or epinephrine causes the activation of adenylate cyclase resulting in the production of cyclic AMP, which activates protein kinase A. By phosphorylation reactions, protein kinase A inactivates glycogen synthase, activates a cascade that results in active glycogen phosphorylase, and produces an active inhibitor of protein phosphatase 1.

The effect of phosphorylation on glycogen synthase activity and relative effects of... 

In vitro studies Phosphorylation of the glycogen synthase activity leads to decreased activity but phosphorylations at different sites have different effects. Little or no inactivation is seen with phosphorylation at sites 5, la, and lb while phosphorylation of site 2 gives moderate inactivation. A most potent inactivation... 

Figure 16.12 Regulation of glycogen synthase activity through cAMP-mediated control of phosphoprotein phosphatase (PP-1) activity. 

Glycogen synthase has also been purified from A. suum muscle and is about 3% of the soluble protein (5). It is converted into an inactive o-form when phosphorylated by ox heart cAMP-dependent protein kinase and binds about 1 mol of phosphate/mol of subunit. A second glycogen synthase activity has also been described and purified from... 

Semiz S, Oevig C and McNeill JH (2002) Effects of diabetes, vanadium, and insulin on glycogen synthase activation in Wistar rats. Mol Cell Biochem 231 23-35. 

Damsbo P, Vaag A, Hother-Nielsen O, et al. Reduced glycogen synthase activity in skeletal muscle from obese patients with and without type 2 (non-insulin-dependent) diabetes mellitus. Diabetologia 1991 34(4) 239-245. 

Insulin Liver Increased glucokinase increased glucose uptake Increased glycogen synthase activity glycogen deposition Inhibited gluconeogenesis Increased malic enzyme, acetyl-CoA carboxylase, fatty acid synthetase and stearoylCoA desaturase increased lipogenesis Release of VLDL from hepatocytes... 

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