Glycogen phosphorylase/synthase

Figure 4. Glycogen phosphorylase/synthase. Phos., phosphorylase regulatory subunit of protein kinase (cf, protein modifiers, this chapter. Section II.F.l.) denotes that degree of phosphorylation is variable, providing for a continuum of activity in the presence of G-6-P Lpo4 indicates this form of the enzyme is phosphorylated.

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. 

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

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...

The glucose concentration is the major factor regulating glycogen synthesis in liver. Glucose activates glucokinase directly as a substrate and indirectly via an increase in the concentration of fructose 6-phosphate. It also activates glycogen synthase but it inhibits glycogen phosphorylase (see text). 

Figure 6.31 (a) An increase in the intracellular concentration of glucose in the liver results in an increased activity of glycogen synthase and a decreased activity of glycogen phosphorylase. The mechanisms for these effects are shown in (b). 

GLYCOGEN PHOSPHORYLASE 1,3-y3-G LUCAN SYNTHASE GLUCARATE DEHYDRATASE D-Glucitol,... 

GLUCOSE TRACER KINETICS GLYCOGEN PHOSPHORYLASE GLYCOGEN SYNTHASE GLYCOLA.TE OXIDASE... 

Fig. 7.18. Regulation of glycogen metabolism in muscle. Phosphorylase kinase stands at the center of regulation of glycogen metabolism. Phosphorylase kinase may exist in an active, phosphorylated form and an inactive, unphosphorylated form. Phosphorylation of phosphorylase kinase is triggered by hormonal signals (e.g. adrenahne) and takes place via an activation of protein kinase A in the cAMP pathway. In the absence of hormonal stimulation, phosphorylase kinase can also be activated by an increase in cytosolic Ca. The active phosphorylase kinase stimulates glycogen degradation and inhibits glycogen synthesis, in that, on the one side, it activates glycogen phosphorylase by phosphorylation, and on the other side, it inactivates glycogen synthase by phosphorylation.

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.

T Glucokinase (increased expression) T Glycogen synthase I Glycogen phosphorylase T PFK-l (by T PFK-2)... 

T Glycogen phosphorylase I Glycogen synthase I PFK-1 T FBPase-2 i Pyruvate kinase T PEP carboxykinase T Triacylglycerol lipase Perilipin phosphorylation T Acetyl-CoA carboxylase... 

Response of enzyme to phosphorylation Depending on the specific enzyme, the phosphorylated form may be more or less active than the unphosphorylated enzyme. For example, phosphorylation of glycogen phosphorylase (an enzyme that degrades glycogen) increases activity, whereas the addition of phosphate to glycogen synthase (an enzyme that synthesizes glycogen) decreases activity (see p. 132). 

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