Glycogenesis And Glycogenolysis

Question 1

How is glycogen stored in the liver?

Answer 1

Large granules in cytoplasm of hepatocytes

Question 2

What is the difference between muscle glycogen and liver glycogen?

Answer 2

• Muscle: glycogen is broken down into glucose which enters glycolysis and is used to produce energy specifically for muscle cells (ATP)
• Liver: glycogen is broken down into glucose which enters bloodstream and travels to cells which require it e.g. CNS, red blood cells

Question 3

Give 5 examples of tissues which have an absolute requirement for glucose

Answer 3

• Erythrocytes and leukocytes
• Kidney medulla
• CNS
• Lens and cornea of eye
• Testes

Question 4

Describe the structure and composition of glycogen

Answer 4

• Glucose linked by α-1,4 glycosidic bonds (chains) and α-1,6 glycosidic bonds (branching)
• 1 α-1,6 link every 8-10 α-1,4 links so structure is highly branched
• Chains originate from a dimer of the protein GLYCOGENIN which acts as a primer
• Stable compact structure minimise osmotic effects

Question 5

State why glycogenesis can be seen as an anabolic process

Answer 5

Requires an input if chemical energy in the form of ATP and UTP

Question 6

Briefly explain the process of glycogenesis

Answer 6

• Glucose —> Glucose-6-P using Hexokinase and ATP
• Glucose-6-P —> Glucose-1-P using Phosphoglucomutase
• Glucose-1-P —> UDP-Glucose using UTP and uridyl transferase
• UDP-Glucose is added to glycogen chain using Glycogen Synthase (1,4) or Branching Enzyme (1,6)

Question 7

Explain the significance of the branched structure of glycogen

Answer 7

• Compact, so minimises osmotic effect

- Lots of positions for enzymes to bind in order to break down glycogen to glucose quickly so it can be metabolised

Question 8

Explain why glycogenolysis is not simply a reversal of glycogenesis

Answer 8

Different enzymes allow simultaneous inhibition of one pathway and stimulation of another

Question 9

Which 2 enzymes are involved in the breakdown of glycogen to Glucose-1-P?

Answer 9

• Glycogen Phosphorylase breaks α-1,4 links
• De-branching Enzyme breaks α-1,6 links
• Addition of Pi converts UDP-Glucose to Glucose-1-P

Question 10

What is the action of PHOSPHOGLUCOMUTASE?

Answer 10

• Catalyses a reversible reaction of the conversion of Glucose-6-P to Glucose-1-P
• The phosphate group is moved from C6 to C1

Question 11

Explain how Glucose-6-Phosphate is used by liver and muscle cells

Answer 11

• LIVER: converted to Glucose using GLUCOSE-6- PHOSPHATATSE, which enters the blood and is transported to requiring tissues
• MUSCLE: lacks Glucose-6-Phosphatase enzyme so G-6-P enters Glycolysis and is used for local energy production in muscle cells

Question 12

What is ‘branching enzyme’?

Answer 12

Enzyme used to form α-1,6 glycosidic links between UDP-glucose residues for storage as glycogen

Question 13

What is GLUT4?

Answer 13

• Insulin sensitive glucose transporter found in plasma membrane of muscle cells
• Allows uptake of glucose into cells and is stimulated by insulin and inhibited by glucagon

Question 14

What is GLUT2?

Answer 14

Glucose transporter found in plasma membrane of liver cells and pancreatic beta cells which can transport glucose both in and out of the cell (out to glucose-dependant tissues)

Question 15

What is the effect of Glucagon on Glycogen Phosphorylase in MUSCLE.

Answer 15

• NO EFFECT

- AMP is an allosteric activator of muscle glycogen phosphorylase but not of liver glycogen phosphorylase

Question 16

Explain the effect of Insulin on glycogenesis and glycogenolysis

Answer 16

• Dominates during fed state (need to store excess glucose as glycogen in order to lower blood glucose levels)
• INCREASES ACTIVITY of Glycogen Synthase so promotes glycogenesis
• DECREASES ACTIVITY of Glycogen Phosphorylase so suppresses glycogenolysis

Question 17

Explain the effect of Glucagon/Adrenaline on glycogenesis and glycogenolysis

Answer 17

• Dominates during fasted state (need to utilise glycogen stores in order to raise blood glucose levels)
• INCREASES ACTIVITY of Glycogen Phosphorylase so promotes glycogenolysis
• DECREASES ACTIVITY of Glycogen Synthase so suppresses glycogenesis

Question 18

How are the enzymes of glycogenesis and glycogenolysis controlled by covalent modification?

Answer 18

• RECIPROCALLY CONTROLLED by reversible phosphorylation
• Glucagon promotes phosphorylation whereas Insulin promotes de-phosphorylation
• Glycogen Synthase is inhibited by phosphorylation and activated by de-phosphorylation
• Glycogen Phosphorylase is activated by phosphorylation and inhibited by de-phosphorylation

Question 19

What are the consequences of glycogen storage diseases?

Answer 19

Increased or decreased amounts of glycogen can lead to:

• Tissue damage if stored excessively
• Fasting HYPOGLYCAEMIA
• Poor exercise tolerance

Question 20

Explain why only the liver or the muscle may be affected in glycogen storage diseases

Answer 20

Muscle glycogen phosphorylase and liver glycogen phosphorylase are coded for by different genes so mutation may only affect one of them

Question 21

How is glycogen stored in muscle?

Answer 21

Stored as granules both intermyofibrilly (between myofibrils) and intramyofibrilly (inside fibrils)

Question 22

What is von Gierke’s disease?

Answer 22

• GLYCOGEN STORAGE DISEASE
• Glucose-6-phosphatase deficiency
• Affects liver but not muscle