Glycogen synthases

Glycogen Synthase Catalyzes Formation of a-(l 4) Glycosidic Bonds in Glycogen... 

Glycogen synthase also exists in two distinct forms which can be interconverted by the action of specific enzymes active, dephosphorylated glycogen synthase I (glucose-6-P-independent) and less active phosphorylated glycogen synthase D (glucose-6-P-dependent). The nature of phosphorylation is more complex with glycogen synthase. As many as nine serine residues on the enzyme appear to be subject to phosphorylation, each site s phosphorylation having some effect on enzyme activity. 

Dephosphorylation of both glycogen phosphorylase and glycogen synthase is carried out by phosphoprotein phosphatase 1. The action of phosphopro-tein phosphatase 1 inactivates glycogen phosphorylase and activates glycogen synthase. 

Suggest an explanation for the exergonic nature of the glycogen synthase reaction (AG° = - 13.3 kj/mol). Consult Chapter 3 to review the energetics of high-energy phosphate compounds if necessary. 

Earner, J., 1990. Insulin and the stimulation of glycogen synthesis The road from glycogen structure to glycogen synthase to cyclic AMP-dependent protein kinase to insulin mediators. Advances in Enzymology 63 173-231. 

Glycogen synthesis 1 Muscle glycogen synthase l Activity Muscle... 

GSK3 phosphorylates glycogen synthase (GS), the key enzyme for glycogen synthesis which builds up the... 

Liver Activation of glycogen synthesis Activation of glycogen synthase (GS) Inactivation of glycogen synthase kinase 3 (GSK3) through phosphorylation by Akt... 

In the frame of a medicinal project at J J Pharmaceutical Research and Development aimed at designing new potent and selective glycogen synthase kinase-3/i (GSK-3/3) inhibitors, the C-3 derivatization of the 1-methyl-4-[l-alkyl-lff-indol-3-yl]-lff-pyrrole-2,5-dione scaffold was explored [31]. Microwave-assisted Stille reaction of 3-chloro-l-methyl-4-[l-alkyl-lff-indol-3-yl]-lH-pyrrole-2,5-diones with (2,4-dimethoxy-5-pyrimidinyl)(tributyl) stannane at 200 °C yielded in 6 min the desired 3,4-diaryl-lff-pyrrole-2,5-diones in moderate yields (Scheme 12). 

Nserum L, Nprskov-Lauritsen L, Olesen PH. Scaffold hopping and optimization towards libraries of glycogen synthase kinase-3 inhibitors. Bioorg Med Chem Lett 2002 12 1525-8. 

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

Glycogen Synthase Phosphorylase Activity Are Reciprocally Regulated (Figure 18-7)... 

Like phosphorylase, glycogen synthase exists in either a phosphorylated or nonphosphorylated state. However, unlike phosphorylase, the active form is dephosphorylated (glycogen synthase a) and may be inactivated to... 

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.)...

REGULATION OF GLYCOGEN METABOLISM IS EFFECTED BY A BALANCE IN ACTIVITIES BETWEEN GLYCOGEN SYNTHASE PHOSPHORYLASE (Figure 18-8)... 

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,... 

The breakdown of glycogen to glucose 1-phosphate is catalyzed by phosphorylase. Glycogen synthesis involves a different pathway via uridine diphosphate glucose and glycogen synthase (Figure 18-1). 

Enzymes of glycogenes Glycogen synthase system is,glycoiy T sis, and py T ruvate oxidation Insulin Insulin Glucose 6-phosphate Glucagon (cAMP) phos-phorylase, glycogen... 

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