Glycogen Metabolism - Control of Glycogen Metabolism Flashcards
(28 cards)
If the glycogen synthesis and breakdown pathways operate simultaneously, what is achieved?
Wasteful hydrolysis of UTP
What stringent control must glycogen phosphorylase and glycogen synthase be under?
Glycogen must either be synthesized or utilized according to cellular needs
What do the mechanism that controls glycogen phosphorylase and glycogen synthase involve?
- Allosteric control and substrate cycles
- Enzyme-catalyzed covalent modification of both glycogen synthase and glycogen phosphorylase under hormonal control through an enzymatic cascade
Which effectors allosterically control the rates of glycogen phosphorylase and glycogen synthase reactions?
- ATP
- G6P
- AMP
In muscle, what activates and inhibits glycogen phosphorylase?
Activated by AMP and inhibited by ATP and G6P
What activates glycogen synthase?
G6P
What happens to glycogen phosphorylase and glycogen synthase when there is low [ATP] and [G6P] and high [AMP]?
Glycogen phosphorylase is stimulated and glycogen synthase is inhibited - flux through this pathway favours glycogen breakdown *high demand for ATP
What happens to glycogen phosphorylase and glycogen synthase when there is high [ATP] and [G6P] and low [AMP]?
Glycogen synthase is stimulated and glycogen phosphorylase is inhibited - flux through this pathway favours glycogen synthesis *low demand for ATP
What are the T and R confirmations of glycogen phosphorylase?
- T state is inactive: Enzyme has buried active site and low affinity for its substrates
- R state is active: Enzyme has an accessible catalytic site and high-affinity phosphate-binding site
What promotes phosphorylase’s T (inactive) to R (active) conformation? How?
AMP by binding to the R state of the enzyme at its allosteric effector site
How can ATP inhibit the T–>R conformational shift?
By binding to the allosteric effector site in the T state
How is the inhibitory action of ATP on phosphorylase simply understood?
It competes with AMP for binding to phosphorylase, and in doing so, prevents the relative motions of the three polypeptide segments required for phosphorylase activation
How can glycogen synthase and glycogen phosphorylase each be enzymatically interconverted between two forms with different kinetic and allosteric properties?
Through a complex series of reactions known as a cyclic cascade
What does the interconversion of these different enzyme forms involve?
Distinct, enzyme-catalyzed covalent modifications and demodification reactions
What can enzymatically interconvertible enzyme systems do?
1) Respond to a greater number of allosteric stimuli
2) Exhibit greater flexibility in their control patterns
3) Possess enormous amplification potential in their responses to variations in effector concentrations
How are the two forms of glycogen phosphorylase activated?
- glycogen phosphorylase b requires AMP for activity
- glycogen phosphorylase a is active without AMP
What do phosphorylases a and b correspond to?
Forms of the protein in which a specific residue, Ser 14, is enzymatically phosphorylated or dephosphorylated
How is the activity of glycogen phosphorylase allosterically controlled?
Through AMP activation and ATP, G6P, and glucose inhibition
What enzymes are involved in the activation of glycogen phosphorylase and what do they phosphorylate or dephosphorylate?
1) Phosphorylase kinase: Specifically phosphorylates Ser 14 of glycogen phosphorylase b
2) Protein kinase A: Phosphorylates and thereby activates phosphorylase kinase
3) Phosphoprotein phosphatase-1: Dephosphorylates and thereby deactivates both glycogen phosphorylase a and phosphorylase kinase
What is the level of phosphorylase activity largely determined by?
The function of the enzyme present as phosphorylase a
What does phosphorylase kinase convert?
phosphorylase b to phosphorylase a
When does phosphorylase kinase become fully active?
When Ca2+ is present and the protein is phosphorylated
What is the cAMP concentration in a cell a function of?
The ratio of its rate of synthesis from ATP by adenylate cyclase (AC or adenylyl cyclase) and its rate of breakdown to AMP by enzymes known as cAMP-phosphodiesterases (cAMP-PDEs)
What is cAMP absolutely required for?
The activity of protein kinase A [PKA; cAMP-dependent protein kinase (cAPK)]
