Glycogen Metabolism - Control of Glycogen Metabolism

Question 1

If the glycogen synthesis and breakdown pathways operate simultaneously, what is achieved?

Answer 1

Wasteful hydrolysis of UTP

Question 2

What stringent control must glycogen phosphorylase and glycogen synthase be under?

Answer 2

Glycogen must either be synthesized or utilized according to cellular needs

Question 3

What do the mechanism that controls glycogen phosphorylase and glycogen synthase involve?

Answer 3

• Allosteric control and substrate cycles
• Enzyme-catalyzed covalent modification of both glycogen synthase and glycogen phosphorylase under hormonal control through an enzymatic cascade

Question 4

Which effectors allosterically control the rates of glycogen phosphorylase and glycogen synthase reactions?

Answer 4

• ATP
• G6P
• AMP

Question 5

In muscle, what activates and inhibits glycogen phosphorylase?

Answer 5

Activated by AMP and inhibited by ATP and G6P

Question 6

What activates glycogen synthase?

Answer 6

G6P

Question 7

What happens to glycogen phosphorylase and glycogen synthase when there is low [ATP] and [G6P] and high [AMP]?

Answer 7

Glycogen phosphorylase is stimulated and glycogen synthase is inhibited - flux through this pathway favours glycogen breakdown *high demand for ATP

Question 8

What happens to glycogen phosphorylase and glycogen synthase when there is high [ATP] and [G6P] and low [AMP]?

Answer 8

Glycogen synthase is stimulated and glycogen phosphorylase is inhibited - flux through this pathway favours glycogen synthesis *low demand for ATP

Question 9

What are the T and R confirmations of glycogen phosphorylase?

Answer 9

• 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

Question 10

What promotes phosphorylase’s T (inactive) to R (active) conformation? How?

Answer 10

AMP by binding to the R state of the enzyme at its allosteric effector site

Question 11

How can ATP inhibit the T–>R conformational shift?

Answer 11

By binding to the allosteric effector site in the T state

Question 12

How is the inhibitory action of ATP on phosphorylase simply understood?

Answer 12

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

Question 13

How can glycogen synthase and glycogen phosphorylase each be enzymatically interconverted between two forms with different kinetic and allosteric properties?

Answer 13

Through a complex series of reactions known as a cyclic cascade

Question 14

What does the interconversion of these different enzyme forms involve?

Answer 14

Distinct, enzyme-catalyzed covalent modifications and demodification reactions

Question 15

What can enzymatically interconvertible enzyme systems do?

Answer 15

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

Question 16

How are the two forms of glycogen phosphorylase activated?

Answer 16

• glycogen phosphorylase b requires AMP for activity
• glycogen phosphorylase a is active without AMP

Question 17

What do phosphorylases a and b correspond to?

Answer 17

Forms of the protein in which a specific residue, Ser 14, is enzymatically phosphorylated or dephosphorylated

Question 18

How is the activity of glycogen phosphorylase allosterically controlled?

Answer 18

Through AMP activation and ATP, G6P, and glucose inhibition

Question 19

What enzymes are involved in the activation of glycogen phosphorylase and what do they phosphorylate or dephosphorylate?

Answer 19

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

Question 20

What is the level of phosphorylase activity largely determined by?

Answer 20

The function of the enzyme present as phosphorylase a

Question 21

What does phosphorylase kinase convert?

Answer 21

phosphorylase b to phosphorylase a

Question 22

When does phosphorylase kinase become fully active?

Answer 22

When Ca2+ is present and the protein is phosphorylated

Question 23

What is the cAMP concentration in a cell a function of?

Answer 23

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)

Question 24

What is cAMP absolutely required for?

Answer 24

The activity of protein kinase A [PKA; cAMP-dependent protein kinase (cAPK)]

Question 25

What important cellular proteins does PKA phosphorylate?

Answer 25

Phosphorylase kinase and glycogen synthase

Question 26

In the absence of cAMP, what is PKA?

Answer 26

An inactive heterotetramer consisting of two regulatory and two catalytic subunits

Question 27

What does the intracellular concentration of cAMP determine?

Answer 27

The fraction of PKA in its active form and thus the rate at which it phosphorylates its substrates

Question 28

In all known eukaryotic cases, how are the physiological effects of cAMP exerted?

Answer 28

Through the activation of specific protein kinases