Energy Storage

Question 1

What is the difference between muscle and liver glycogen stores?

Answer 1

• Muscle glycogen is made up of Glucose-6-Phosphate, it’s only utilised by muscle cells
• Muscle lacks the enzyme Glucose-6-Phosphotase so G-6-P enters glycolysis. Liver has this enzyme, so glucose is released by liver into blood for use by other tissues

Question 2

Describe the process of Glycogenolysis

Answer 2

Step 1:

• Glycogen (n residues) + Pi is converted into Glucose-1-Phosphate and Glycogen (n-1 residues)
• Glycogen Phosphorylase or Debranching Enzyme catalyses this

Step 2:

-Glucose-1-Phosphate converted into Glucose-6-Phosphate via Phosphoglucomutase

Question 3

Describe the process of Glycogenesis

Answer 3

Step 1:

• Glucose + ATP converted into Glucose 6-Phosphate and ADP
• Hexokinase used (Glucokinase in liver)

Step 2:

• Glucose 6-Phosphate converted into Glucose 1-Phosphate via Phosphoglucomutase
• Reversible

Step 3:

-Glucose 1-Phosphate + UTP + H20 converted into UDP-Glucose and 2Pi

Step 4:

• Glycogen (n residues) + UDP-Glucose converted into Glycogen (n+1 residues) and UDP
• via Glycogen synthase or Branching enzyme

Question 4

Describe the process of Gluconeogenesis

Answer 4

Three major precursors:

Lactate- from anaerobic glycolysis in exercising muscle and red blood cells

Glycerol- released from adipose tissue breakdown of triglycerides

Amino Acids- mainly alanine

Key Enzymes in Gluconeogenesis

1) Phosphoenolpyruvate carboxykinase (PEPCK)
2) Fructose 1,6- bisphosphotase
3) Glucose-6-phosphotase

Question 5

How is liver glycogen metabolism regulated?

Answer 5

Glycogen Synthase is rate limiting enzyme in Glycogen Synthesis

Glycogen Phosphorylase is rate limiting enzyme in Glycogen degradation

• Glucagon and adrenaline act on glycogen synthase via phosphorylation, decreasing enzyme activity
• Glucagon and adrenaline acts on glycogen phosphorylase via phosphorylation, increasing enzyme activity
• Insulin does the opposite

NOTE:

Glucagon has no effect on muscle glycogen stores
AMP is an allosteric activator of muscle glycogen phosphorylase but not the liver form of the enzyme

Question 6

Explain how glucose can be obtained from non-carbohydrate sources

Answer 6

• Gluconeogenesis
• Substrates can be pyruvate, lactate, glycerol, amino acids whose metabolism involves pyruvate or krebs cycle intermediates (oxaloacetate)

-Glycolysis, irreversible steps bypassed

Question 7

Discuss the clinical relevance of glycogen storage diseases

Answer 7

-Inborn errors of metabolism

-Arise from deficiency or dysfunction of enzymes of glycogen metabolism
11 distinct types. Incidence varies from 1 in 20,000 to 1 in 1,000,000

• Excess glycogen storage can lead to tissue damage
• Diminished glycogen stores can lead to hypoglycaemia and poor exercise tolerance

Examples:

• von Gierke’s disease- Glucose 6-Phosphatase deficiency
• Macrocell’s disease- muscle glycogen phosphorylase deficiency

Question 8

When and where does gluconeogenesis occur?

Answer 8

• Beyond 8 hours of fasting, liver glycogen stores start to deplete and an alternative source of glucose is required
• Occurs in Liver and to lesser extent in kidney cortex

precursors are lactate, glycerol, amino acids esp. alanine

Question 9

How is gluconeogenesis controlled?

Answer 9

• Glucagon and Cortisol stimulate PEPCK and Fructose 1,6 bisphophatase
• Insulin inhibits PEPCK and Fructose 1,6 bisphosphotase