Glycogen synthetase phosphorylation

Glycogen synthetase I Vl r Glvcooen synthetase P (nonphosphorylated < (phosphorylated... 

Many enzymes may be activated or inhibited by phosphorylation. -Pyruvate dehydrogenase and glycogen synthetase are inhibited... 

The less active phosphorylated form of glycogen synthetase is dephos-phorylated, causing the enzyme to become active. Insulin causes activation of the phosphatase that catalyzes this reaction. 

Phosphoproteins.— Details of the amino-acid sequences at the phosphorylation sites of two proteins involved in glycogen metabolism have been published, and they show unusual features. For example, there is an unusually high proportion of hydroxyl side-chains near the phosphoserine at one of the phosphorylation sites in glycogen synthetase, ... 

A non-phosphorylated form of glycogen phosphorylase B (EC 2.4.1.1) has been isolated from rabbit liver.Co-operative interactions between the substrate-binding sites become more pronounced in the presence of inhibitors, ATP, and D-glucose, and less pronounced in the presence of the activator AMP. Isoenzymes of glycogen phosphorylase and glycogen synthetase are preserved in chick embryo liver and in the liver of adult chicken. The changes which were observed in the ratio between phosphorylases a and b, on the one hand, and glycogen synthetases I and D on the other, do not fit into the Hers scheme for the liver of adult mammals. 

Glycogen synthetase (11.49) occurs in active unphosphorylated (A) and inactive phosphorylated (B) forms which can be inter-converted by appropriate enzymes. 

A good illustration of the regulatory properties of cAMP occurs in liver stimulated by glucagon. cAMP activates a protein kinase which phosphorylates both phosphorylase and glycogen synthetase, but while phosphorylase is activated, glycogen synthetase is inhibited by the phosphorylation. Consequently, cAMP at the same time stimulates glycogen breakdown and inhibits glycogen synthesis. 

Soderling, T. R., Hickenbottom, J. P., Reimann, E., Hunkeler, F. L., Walsh, D. A., and Krebs, E. G., 1970, Inactivation of glycogen synthetase and activation of phosphoryl-ase kinase by muscle adenosine 3, 5 -monophosphate-dependent protein kinases, /. Biol. Chem. 245 6317. 

Covalent interconversion of enzymes is well established as a fundamental theme in metabolic regulation. The prototypic reversible interconverting systems include the sequence of phosphorylation/dephosphorylation steps in the activation of mammalian glycogen phosphorylase and pyruvate dehydrogenase as well as the nucleotidyla-tion/denucleotidylation using UTP and ATP in the bacterial glutamine synthetase cascade (see Fig. 1.). 

A. Phosphorylation - dephosphorylation Phosphorylation of Ser, Thr Phosphorylation of Tyr Adenylylation, Uridylylation ADP-ribosylation Glycogen phosphorylase Insulin receptor Glutamine synthetase This section Section G Chapter 25 This section... 

Then that kinase starts a cascade of enzyme activity By phosphorylation altering their style So the synthetase for glycogen can change from a to b And slow synthetic action for a while. 

Enzyme activity can be regulated by covalent modification or by noncovalent (allosteric) modification. A few enzymes can undergo both forms of modification (e.g., glycogen phosphorylase and glutamine synthetase). Some covalent chemical modifications are phosphorylation and dephosphorylation, acetylation and deacetylation, adeny-lylation and deadenylylation, uridylylation and deuridyly-lation, and methylation and demethylation. In mammalian systems, phosphorylation and dephosphorylation are most commonly used as means of metabolic control. Phosphorylation is catalyzed by protein kinases and occurs at specific seryl (or threonyl) residues and occasionally at tyrosyl residues these amino acid residues are not usually part of the catalytic site of the enzyme. Dephosphorylation is accomplished by phosphoprotein phosphatases ... 

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