Lecture 4 & 5: Haemoglobin as a model protein

Question 1

What is haemoglobins function?

Answer 1

• blood oxygen transport around the body

- —> reversible oxygen carriage

Question 2

What is the structure of haemoglobin?

Answer 2

• tetramer - 4 pyrrole rings linked by methene bridges
• Fe2+ in its ferrous state is located in the middle and is attached to the haem by 4 nitrogen atoms
• 2-alpha & 2-beta chains

Question 3

How is heme & globin arranged in haemoglobin?

Answer 3

Each subunit has a heme group & globin protein, so the overall haemoglobin protein is able to carry 4 O2 molecules.
- Ferrous Fe2+ is located in the centre

Question 4

How does Haemoglobin display co-operative behaviour?

Answer 4

• subunits co-operate with each other
• –> the binding of O2 to one subunit of the Hb tetramers induce sa conformation change in the subunit. This conformation change is transmitted to adjacent subunits which makes the binding of O2 to other subunits easier

Question 5

What happens to haemoglobin as oxygen binds to one of the subunits?

Answer 5

When O2 binds to one of the subunits, it influences neighbouring units to take up more oxygen easier
- when the oxygen binds to the haem, the HisF8 drops down which causes a shift in the F helix which changes the shape of the other subunits

Question 6

What is the function of myoglobin?

Answer 6

• Stores and releases oxygen when needed

Question 7

What is the structure of myoglobin?

Answer 7

• A monomer & consists of a haem group & globin protein.
• The haem containing Fe2+ is located within a hydrophobic cleft of globin
• 8 alpha helices

Question 8

What are the major differences btw myoglobin and haemoglobin’s ability to bind oxygen?
- MYOGLOBIN

Answer 8

• Is saturated with Ox at low pressure of O2
• —> myoglobin has a high affinity to O2
• —-> won’t release its O2 until levels of O2 are low
• —> acts as a reservoir of oxygen - stores O2
• —> O2 is easily attached but released at very low pressures of O2

Question 9

What are the major differences btw myoglobin and haemoglobin’s ability to bind oxygen?
- HAEMOGLOBIN?

Answer 9

• Is a tetramer and its units cooperate with each other
• —> O2 is bound/released gradually as the subunits influence each other
• —-> hard to get the first O2 bound but due to allosteric behaviour addition oxygen binding is easier

Question 10

What is the Bohr effect?

Answer 10

H+ and CO2 both bind to haemoglobin & affect the affinity of haemoglobin for oxygen
—-> the affect of H+ is called the Bohr effect
As H+ increases (pH decreases) the oxygen binding affinity of haemoglobin is reduced

Question 11

How does BPG change the oxygen-binding characteristics of haemoglobin?

Answer 11

In the presence of BPG the affinity of oxygen binding to haemoglobin is reduced significantly.
—> oxygen is released from HbA in peripheral tissues where oxygen is being taken up by cell to enable aerobic metabolism