Glycogen Metabolism

Question 1

Which linkages are used to form glycogen?

Answer 1

α-D-GLUCOPYRANOSIDE

Question 2

α-1,6 linkage and α-1,4 linkage. What are the two linkages used to form ?

Answer 2

Glycogen - the main storage form for glucose in mammalian cells

Question 3

In the fed state glycogen constitutes:

Answer 3

• 10% of the weight of liver
• 2% of the weight of muscle

BUT
- 40% of human body weight is muscle
- 2.5% of human body weight is liver
SO
- More glycogen overall is stored in muscle

Question 4

What is mobilisation ?

Answer 4

In times of metabolic need cells can switch on the breakdown of stored glycogen very rapidly

Question 5

The breakdown products meet different ?

Answer 5

Needs in liver and muscle

Question 6

What is Glycogen broken down to ?

Answer 6

Into Glucose-1-Phosphate then Glucose-6-Phosphate which is a reversible reaction

Question 7

After Glucose-6-Phosphate what is it broken down into ?

Answer 7

Pyruvate which then breaks up into Lactate and CO2 + H2O

Question 8

Muscle mobilises its glycogen to fuel ?

Answer 8

Its own energy requirement via glycolysis

Question 9

What is Liver glycogen converted to ?

Answer 9

Glucose for export to other tissues

Question 10

What does defects in G-6-Phosphatase result in ?

Answer 10

Congenital neutropenia (recurring infections)

Question 11

Why can the liver convert this ?

Answer 11

Because it expresses the enzyme glucose-6-phosphatase which is not present in muscle cells

Question 12

How are the α1-4 linkages are broken by

Answer 12

Phosphorolysis, catalysed by the enzyme (glycogen) Phosphorylase. It bites off single units from the non-reducing end

Question 13

What is Phosphoglucomutase ?

Answer 13

An enzyme that transfers a phosphate group on an α-D-glucose monomer from the 1 to the 6 position in the forward direction or the 6 to the 1 position in the reverse direction

Question 14

What is Phosphorolysis ?

Answer 14

It’s analogous to hydrolysis (with phosphate acting like water in hydrolysis reactions).
- NOTE THAT ATP IS NOT INVOLVED IN THIS REACTION

Question 15

What is Pyridoxal phosphate (PLP) ?

Answer 15

A derivative of vitamin B6, serves as prosthetic group for glycogen phosphorylase

Question 16

How do you regulate glycogen phosphorylase?

Answer 16

The hormones glucagon & epinephrine (adrenalin) activate cAMP cascades in liver and in muscle, respectively, to activate phosphorylase

Question 17

Explain the signal transduction by cAMP ?

Answer 17

• Hormone acts as 1st messenger and activates receptor
• Exchange of GTP for GDP on Gsa leads to activation of Adenylate Cyclase and cAMP formation (2nd messenger)
• cAMP activates cAMP-dependent protein kinase (PKA) resulting in phosphorylation of target protein leading to the physiological response

Question 18

When are both hormones glucagon & epinephrine produced ?

Answer 18

They are produced in response to low blood glucose, thus releasing glucose from glycogen when needed
Epinephrine is also part of the “fight or flight” response and levels rise greatly during exercise when the metabolic demands of muscle are high

Question 19

What happens in the response to epinephrine:

Answer 19

The cAMP cascade results in phosphorylation of a serine hydroxyl of muscle glycogen phosphorylase, which promotes transition to the active (relaxed) state

Question 20

Role of G-proteins ?

Answer 20

• Multiple forms of G protein
• β-adrenergic receptor interacts with Gs (stimulatory) to activate ACase
• Muscarinic receptors interact with Gi (inhibitory) to inhibit ACase

Question 21

Phosphorylase can only break ?

Answer 21

α-1:4-links up to within 4 residues (glucose units) of a branch point.

Question 22

At this point a transferase activity takes?

Answer 22

Three residues and transfers them to the end of another chain

Question 23

The single glucose unit left from the branch is ?

Answer 23

Removed by the action of α-1:6-glucosidase.