Haemoglobin

Question 1

What is the structure of Haemoglobin?

What is the structure of the Haem group?

Answer 1

Tetramer of two alpha and two beta polypeptides
(Myoglobin: single polypeptide of Hb)

Fe atom bound to 4 Nitrogen’s in a protoporphyrin ring and a Histidine residue, leaving space for binding of one O2

Question 2

What is the function of Haemoglobin?

What is the function of Myoglobin?

Answer 2

Haemoglobin: Transport O2 in the blood
Myoglobin: Transport O2 from Haemoglobin to tissue

Question 3

How does oxygen binding change the shape of Haemoglobin and what is this type of binding called?

Answer 3

Moves Fe molecule into plane of the ring (stabilises the R-state of Haemoglobin)
Co-operative binding

Question 4

How is O2 binding to Haemoglobin regulated?

Answer 4

Decreases affinity:
2,3-Bis-Phosphoglycerate (binds to tetramer)
Bohr effect (Active tissue, lower pH - more H+ and CO2 present)
CO (has a higher affinity than Hb)
fHb (has a higher affinity than Hb)

Question 5

What causes sickle-cell anaemia and what is the result to the erythrocyte?

Answer 5

Missense mutation of glutamate to valine in beta-Hb polypeptide
Causes a ‘sticky pocket’ of hydrophobic valine
Structure of the erythrocytes are more rigid (blocking capillaries) and prone to lyse (release Hb strands when they lyse - further blocking capillaries)
Individual deoxygenated Sickle-Hb will polymerise

Question 6

What is thasselaemia?

What are the types?

Answer 6

Genetic disorder of imbalanced alpha and beta globin chains
Alpha: (symptoms appear before birth)
- Decreased/Absent alpha-chains
- beta-chains form tetramers with an increased affinity but unstable
- 2 copies of the alpha-globin gene (therefore varying severity)
Beta: (symptoms appear after birth)
- Decreased/Absent beta-chains
- alpha-chains cannot form tetramers
- 1 copy of the beta-globin gene