Glycogen phosphorylase dephosphorylation

Dephosphorylation of glycogen phosphorylase is carried out by phospho-protein phosphatase 1. The action of phosphoprotein phosphatase 1 inactivates glycogen phosphorylase. 

A well-known example, indeed the first enzyme that was shown to be regulated by the phosphorylation/ dephosphorylation mechanism, is glycogen phosphorylase, which catalyses the breakdown of glycogen (Box 3.7). 

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.). 

Fig. 7.21. Activation of glycogen-bound protein phosphatase I by insulin. Insulin has a stimulating effect on glycogen synthesis by initiating the dephosphorylation and activation of glycogen synthase and the dephosphorylation and inhibition of glycogen phosphorylase. Both enzymes (substrate S in the figure) are dephosphorylated by protein phosphatase PPIG. Insulin mediates the activation of a protein kinase (insulin-sensitive protein kinase) within an insulin-stimulated signal pathway, which phosphorylates and thus activates protein phosphatase PPIG at the PI site.

Many enzymes are regulated by covalent modification, most frequently by the addition or removal of phosphate groups from specific serine, threonine, or tyrosine residues of the enzyme. In the fed state, most of the enzymes regulated by covalent modification are in Ihe dephosphorylated form and are active (see Figure 24.2). Three exceptions are glycogen phosphorylase (see p. 129), fructose bis-phosphate phosphatase-2 (see p. 98), and hormone-sensitive lipase of adipose tissue (see p. 187), which are inactive in their dephosphorylated state. 

The control of glycogen phosphorylase by the phosphorylation-dephosphorylation cycle was discovered in 1955 by Edmond Fischer and Edwin Krebs50 and was at first regarded as peculiar to glycogen breakdown. However, it is now abundantly clear that similar reactions control most aspects of metabolism.51 Phosphorylation of proteins is involved in control of carbohydrate, lipid, and amino acid metabolism in control of muscular contraction, regulation of photosynthesis in plants,52 transcription of genes,51 protein syntheses,53 and cell division and in mediating most effects of hormones. 

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... 

A phosphorylated enzyme may be either more or less active than its dephos-phorylated form. Thus phosphorylation /dephosphorylation may be used as a rapid, reversible switch to turn a metabolic pathway on or off according to the needs of the cell. For example, glycogen phosphorylase, an enzyme involved... 

Fig. 7.9 Comparison of the allosteric regulation of gycogen phosphorylase with covalent regulation by phosphorylation dephosphorylation. The role of protein phosphatases in regulation was realized for the first time more than 50 years ago, as a cellular enzyme activity that converts the active a form of glycogen phosphorylase to an inactive b form.23...

There must be a way to shut down the high-gain system of glycogen breakdown quickly to prevent the wasteful depletion of glycogen after energy needs have been met. Indeed, another cascade leads to the dephosphorylation and inactivation of phosphorylase kinase and glycogen phosphorylase. Simultaneously, glycogen synthesis is activated. 

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