Glycogen metabolism in the muscle and liver

Question 1

Glycogen

Answer 1

Polysaccharide- storage of glucose (alpha-D-glucose units).

Branched structure, every 8-14 units:
alpha 1-4 bonds linearly
alpha 1-6 bonds branched
- This branched structured allows rapid breakdown via enzymes.

When broken down in glycogenolysis:
Produces glucose-1-phosphate units

Question 2

Sources of glucose in the blood at:

• 2-3 hrs after meal
• 12-24 hrs after meal
• > 24 hrs after meal
• During sleep

Answer 2

2-3 hrs after meal: dietary glucose. Absorbed from intestinal mucosa.

12-24 hrs after meal:
Glycogen storage from previous glycogenesis.

> 24 hrs after meal:
Glycogen stores depleted. Gluconeogenesis from amino acids and glycerols

During sleep: gluconeogenesis

Question 3

Glycogen breakdown in muscle

Answer 3

Glycogen —> G1P —-> G6P

G6P enters glycolysis and is converted to pyruvate.

Pyruvate —> lactate and CO2

Question 4

Glycogen breakdown in the liver

Answer 4

Glycogen —> G1P —> G6P

G6P is converted to glucose via Glucose-6-phosphatase.

This glucose can be released in the blood

Question 5

Enzyme that converts G6P to glucose

Answer 5

Glucose-6-phosphatase

This enzyme is present in the liver but not the muscle.

Question 6

Phosphorolysis of glycogen

Answer 6

Mechanism of breaking down glycogen where phosphate ions are added to glycogen.
- This breaks down alpha 1-4 bonds—> releases G6P

This is done catalysed by glycogen phosphorylase.

This process is not active.

Question 7

Enzyme that breaks alpha 1-4 bonds in glycogen

Answer 7

Glycogen phosphorylase

It can only break up bonds up to 4 glucose units from a branch point.
- releases Glucose-1-phosphate

Question 8

Debranching of glycogen

Answer 8

Performed by transferase and alpha 1-6 glucosidase.

1. Removes 3 units of glucose from branch and transfers it to the linear chain of glucose—-> makes 1-4 bond.
2. Alpha 1-6 glucosidase breaks 1-6 bond at the branch to release free glucose—> hydrolysis mechanism

Question 9

Enzyme that breaks 1-6 bond in glycogen

Answer 9

Alpha 1-6 glucosidase

Does this through a hydrolysis mechanism to release free glucose.

Question 10

Glycogen synthesis

Answer 10

Occurs in the liver and muscle:
1. Glucose—> G6P using Hk/ glucokinase

2. G6P—-> G1P, using mutase enzyme.
3. G1P + UTP —> UDP-glucose
4. UDP-glucose + glycogen—-> Glycogen (n+1) + UDP
   - This uses glycogen synthase

Question 11

Glycogen synthase

Answer 11

Enzyme in glycogen synthase that adds glucose to glycogen via 1-4 bond.

Catalysis UDP-glucose + glycogen.

Question 12

Forming a pre-existing glycogen chain

Answer 12

Uses protein glycogenin:
Adds glucose from UDP-glucose to tyrosine on glycogenin.

This starts the glycogen chain.

UDP-glucose can now add glucose units via 1-4 bonds until glycogen synthase can be used.

Question 13

Synthesis of branches in glycogen

Answer 13

Branching enzyme.

Forms 1-6 bonds by taking 7 units from existing linear chain.

This branching leaves at least 4 units from pre-existing glycogen branch.

Question 14

Benefits of glycogen as an energy store

Answer 14

It can be mobilised rapidly.

Phosphorylase and glycogen synthase are very sensitive to hormone, stress and muscle contraction regulation.

Branched structure= easy access of enzymes

Question 15

Cons of glycogen as an energy store

Answer 15

Glucose is very hydrophilic= heavier weight due to association with water.

Question 16

Allosteric regulation of glycogen phosphorylase.

Answer 16

The following inhibits its activation:
Muscle: ATP, G6P
Liver: High glucose supply, high G6P.

Activates phosphorylase:
Muscle: AMP- indicates low ATP levels.

Question 17

Allosteric regulation of glycogen synthase.

Answer 17

G6P in excess activates synthase.

Also activated by plentiful ATP

Question 18

Protein kinase regulation of glycogen phosphorylase

Answer 18

Phosphorylation by a protein kinase activates phosphorylase.

The mechanism os cAMP dependent.

Phosphorylated phosphorylase is less sensitive to allosteric regulation so will remain active at high ATP and G6P.

Question 19

Protein phosphotase regulation of glycogen phosphorylase

Answer 19

Phosphorylase is de-phosphorylated which makes it less active.

This makes phosphorylase more dependent on allosteric controls.

Question 20

Protein kinase regulation of glycogen synthase

Answer 20

Phosphorylation of synthase makes it less active. Inducing cAMP cascade, deactivates synthase.
- Here it is more dependent on allosteric controls.

This inhibits glycogen synthesis.

Question 21

Protein phosphotase regulation of glycogen synthase

Answer 21

De-phosphorylation of synthase activates the enzyme.

- Inhibiting cAMP activates synthase.