Regulation of Glycogenolysis

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How can norepinephrine induce glycogenolysis?

induces glycogenolysis via α-adrenergic receptors without any other receptor stimulation.

How is glycogen phosphorylase (GPP) phosphorylated /activated?

Phosphorylase kinase b is converted into its highly active state, phosphorylase kinase a, to phosphorylate glycogen phosphorylase. NOTE: PKA phosphorylates phosphorylase kinase & GSK-3. GSK-3 can also activate glycogen phosphorylase.

What are the two distinct conformational states of Glycogen phosphorylase (GPP)?

Glycogen phosphorylase (GPP) is a homodimeric enzyme that exists in two distinct conformational states: a T (for tense, less active) and R (for relaxed, more active) state.

How does phosphorylation affect Glycogen phosphorylase? Does GPP predominate in the R or T forms?

Phosphorylation also influences activity; GPP-a is phosphorylated while GPP-b is not. GPP-a and GPP-b can both exist in the R or T form. GPP-a predominates in the R form while GPP-b predominates in T form. R forms are enhanced when there is reduced G6P.

What is the balance between glycogen phosphorylase -a and -b and T and R forms of glycogen phosphorylase (GPP) dependent upon?

the degree of phosphorylation, and cellular levels of AMP, ATP, and G6P. Adrenergic and glucagon receptors are coupled to activation of adenylate cyclase which increases cAMP (figure 36).

How is the rate of glycogenolysis affected when phosphorylated glycogen phosphorylase a is formed (GPP-a)?

Glycogenolysis increases when phosphorylated glycogen phosphorylase-a is formed (predominant as R form) when there are reduced levels of G6P and ATP (indicated by increase Pi).

What forms of GPP-a or GPP-b does increased ATP or G6P favor?

Increased ATP or glucose-6-phosphate (G6P) favors T forms of either GPP-a or GPP-b due to the energy surplus. This reduces glycogenolysis when plasma [glucose] is elevated, as in after a meal.

Which form, R or T-form of either GPP-a or GPP-b ensures that glycogenolysis will continue but at a very reduced rate?

The T form, of either GPP-a or GPP-b, has greatly reduced activity but ensures that glycogenolysis will continue, but at a very reduced rate, even when high plasma glucose levels are present. Binding of AMP (not cAMP) also favors conversion to GPP-a, where the T form predominates. This ensures that liver cells will have sufficient glucose in the post prandial period since glucokinase has a reduced affinity for glucose.

What is the effect of epinephrine on glycogen phosphorylase activity (GPP)?

This catecholamine neurotransmitter binds to α-adrenergic receptors, stimulating glycogen phosphorylase and inhibiting glycogen synthesis, especially in muscle cells which lack glucagon receptors.

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