Oxygen Transport

Question 1

What is the main differences between haemoglobin and myoglobin?

Answer 1

Haemoglobin is made of four proteins chains whereas myoglobin is only made if two.
Myoglobin has a higher affinity for oxygen than haemoglobin

Question 2

Why does oxygen have to bind to haemoglobin to be transported?

Answer 2

Because oxygen is non polar. Therefore, it does not readily dissolve in blood and so needs a vessel (haemoglobin) to carry it around.

Question 3

Describe the composition of the haem group

Answer 3

• It is a planar molecule
• It consists of a protoporphyrin ring and an Fe atom bound to 4N atoms of the ring
• The Iron ion can make two additional binds to oxygen on either side of the plane.

Question 4

How is the iron ion bound to the protein?

Answer 4

The Iron ion is bound to the protein via a histidine residue (proximal histidine) on the other side of the ring. This leaves one binding site for the oxygen to reversibly bind to.

Question 5

Describe the myoglobin structure

Answer 5

• It is a small protein (made of only 153 amino acids)
• It is compacts. It is a globular and folded
• It is made of 75% alpha helixes
• Histidine 93 in the 8th alpha helix is covalently bonded to iron.

Question 6

Describe what occurs as oxygen binds to myoglobin.

Answer 6

The iron in deoxymyoglobin is slightly below the plane of the porphyrin ring. When oxygen binds, it causes Iron to move into the plane of the ring. This movement then causes the movement of histidine F8 and a small change in the protein conformation.

Question 7

What shape curve does the binding of oxygen to myoglobin produce? Why?

Answer 7

• A hyperbolic curve.
• Oxygen binding to myoglobin shows a hyperbolic dependence on oxygen concentration. This is affinity is constant and it has high affinity for oxygen binding.

Question 8

What shape curve does the binding of oxygen to haemoglobin produce? Why?

Answer 8

• Sigmoidal Curve
• This is because oxygen shows cooperative binding. This means that, as more oxygen molecules bind to the Hb subunits, the affinity for oxygen increase.
• So, it is difficult for the first molecule of oxygen to bind to the first subunit as it has a lot affinity. But, as affinity increases, oxygen binds more easily.

Question 9

Describe the structure of haemoglobin.

Answer 9

• It is made of a total of four polypeptide chains, two alpha (141 aa) and two beta (146 aa) to make a tetramer with a quaternary structure.
• Each chain contains an essential Haem prosthetic group
• Conformation of each polypeptide chain is very similar to that of myoglobin.

Question 10

What two forms can haemoglobin exist in?

Answer 10

Deoxyhaemoglobin can exist in the low affinity T state (can call it the tense state as too tense to join) or a high affinity R state (relaxed so more susceptible to binding). Oxygen only binds when haemoglobin is in the R state. Oxygen binding promotes a change in conformation from T to R and then the stabilisation of the R state.

Question 11

What are the consequences of cooperative binding of oxygen to haemoglobin?

Answer 11

The cooperative binding and the sigmoidal shaped curve of haemoglobin means that oxygen can be more office toy carried form the lungs to the tissues and that it is more sensitive to small differences in concentration of oxygen.
With cooperative binding, 66% of the oxygen in the blood is able to dissociate from haemoglobin and go into tissues. However, if there was no cooperativity, only 38% of the oxygen in the blood would dissociate and go into tissues.

Question 12

How does BPG regulate oxygen binding?

Answer 12

• 2,3-Bisphosphoglycerate (BPG) is present in red blood cells at around a concentration of 5mM.
• It’s role is to lower the affinity of oxygen to haemoglobin so that, in tissues, it dissociates more easily.

Question 13

How does the concentration of BPG change at high altitude and what effect does this have?

Answer 13

At high altitudes, BPG concentrations increase. This shifts the curve to the right (lowers the affinity of oxygen). This is good because it promotes the release of oxygen at tissues to ensure they can still undergo respiration.

Question 14

How do carbon dioxide and protons regulate oxygen binding?

Answer 14

Both H+ and CO2 can bind to haemoglobin molecules.
Binding of H+ and CO2 lowers the affinity of haemoglobin for oxygen.
This is called the Bohr effect. This ensure that the delivery of oxygen if coupled with demand.

Question 15

Why is carbon monoxide a poison?

Answer 15

Carbon monoxide is a poison because it combines with ferromyoglobin and ferrohaemoglobin and blocks oxygen transport.
It binds to haemoglobin 250x more readily than oxygen.
It is fatal when COHb is Over 50%
CO binding also acts to increase the affinity for oxygen for unaffected subunits
Carbon monoxide binds irreversibly. The only way that this can be reversed is by using a hyperbolic chamber.

Question 16

Why do we have many different types of haemoglobin? How does out composition change after birth?

Answer 16

We have many different types of Haemoglobin because different ones have a different impact at different times. HbA most popular in adults. This is made form two alpha and two beta subunits. After birth, the levels if HbF (foetal haemoglobin containing two alpha and two gamma subunits) decreases and the levels of HbA increase.

Question 17

How do we measure how well diabetics control their sugar levels?

Answer 17

Glycosylation (adding of sugars) of HbA forms HbA1c. The levels of HbA1c are used to measure how well sugar levels are controlled

Question 18

Why is it important that a foetus has HbF?

Answer 18

HbF is the major haemoglobin in foetal blood. It has a higher binding affinity for oxygen than HbA which allows the transfer of oxygen from the mother to the foetus (via Hb in the blood).
The sigmoid curve for HbF is further left than that of HbA

Question 19

What causes sickle cell anaemia?

Answer 19

A mutation of Glutamate to Valine in beta globin.

Question 20

What is the consequence of the mutation that causes sickle cell anaemia?

Answer 20

Glutamate is a negatively charged amino acid whereas Valine is hydrophobic. This causes a change in the secondary structure because Valine would like to be on the inside rather than the outside.
This change in secondary structure produces HbS rather than the normal HbA. The “sticky” hydrophobic pocket allows deoxygenated HbS to stick together (polymerise). This mean that oxygen is not transported as well. Also, HbS binds to cell membranes and it does not have as much of a biconcave shape. This makes it more prone to lysis. HbS is more rigid than normal HbA (block microvasculature)

Question 21

What’re thalassaemias?

Answer 21

Thalassaemias are a group of genetic disorders where there is an imbalance between the number of alpha and the number of beta globin chains.

Question 22

What is Beta thalassaemia?

Answer 22

This is when there is decreased or absent Beta-globin chain production.
This means that the alpha chains are unable to form stable tetramers
Symptoms appear after birth

Question 23

What us alpha-thalassaemia?

Answer 23

Decreased or absent alpha-globin chain production.
This is more severe than beta thalassaemia.
There are several different levels of severity due to multiple copies of the alpha-chains being present.
Beta-chains can form stable tetramers with increased affinity for oxygen.
The onset occurs before birth.