Oxygen Transport

Question 1

Why does oxygen need to bind to specific transporters?

Answer 1

Not soluble in water

Question 2

Where is myoglobin found?

Answer 2

Muscle tissue

Question 3

What does Haem consist of?

Answer 3

A protoporphyrin ring and an Fe atom bound to a N atoms of the ring

Question 4

What does oxygen bind to and why?

Answer 4

Haem groups - Fe2+ can make 2 additional bonds to oxygen, one on either side of the plane

Question 5

What is the Fe atom bound to the protein via?

Answer 5

Histidine residue on the other side of the ring

Question 6

What are some features of the structure of myoglobin?

Answer 6

153 amino acids, compact, 75% alpha helical, His 93 in the 8th alpha helix is covalently linked to Fe

Question 7

Where is Fe in deoxymyoglobin?

Answer 7

Slightly below plane of the ring

Question 8

What does oxygen binding do to the Fe in myoglobin?

Answer 8

Moves Fe into plane of the ring which causes movement of His F8 and small change in overall protein conformation

Question 9

What graph does oxygen binding to myoglobin show?

Answer 9

Hyperbolic dependence on oxygen concentration

Question 10

In the graph of the binding of oxygen to myoglobin, what does Y, pO2 and P50 mean?

Answer 10

Y = percentage saturation with oxygen
PO2 = partial pressure of oxygen
P50 = partial pressure giving 50% saturation

Question 11

What is the shape of the oxygen dissociation curve for myoglobin?

Answer 11

Rectangular hyperbola - due to being only one subunit

Question 12

What is the shape of the oxygen dissociation curve for haemoglobin?

Answer 12

Sigmoidal - a consequence of the four subunits co-operating

Question 13

What are some features of haemoglobin structure?

Answer 13

2 polypeptide chains - each containing haem prosethetic group

alpha chain (141 amino acids) and beta chain (146 amino acids) in a a2b2 tetramemer

Question 14

In what two states can deoxyhaemoglobin exist in?

Answer 14

Low affinity T state (tense) ad high affinity R state (relaxed)

Question 15

Which state of deoxyhaemoglobin does oxygen binding promote the stabilisation of?

Answer 15

R state

Question 16

What does oxygen binding to haemoglobin cause?

Answer 16

Change in conformation

Question 17

What is meant by the co-operative binding of oxygen?

Answer 17

Binding affinity for oxygen increases as more oxygen molecules bind to Hb subunits. Binding of the first oxygen molecule is hard as it has a low affinity but it gets progressively easier so that the binding of the last oxygen molecule to the 4th subunit is very easy - has a high affinity.

Question 18

What does the sigmoidal binding curve of haemoglobin mean?

Answer 18

That oxygen can be efficiently carried from lungs to tissues and there is more sensitivity to small differences in oxygen concentrations

Question 19

What effect does 2,3-Bisphosphoglycerate (BPG) have on oxygen binding?

Answer 19

Stabilises T state of haemoglobin so lowers the affinity making it harder for oxygen to bind

Question 20

What is 2,3-BPG present in red blood cells at?

Answer 20

~5mM

Question 21

What happens to the concentration of BPG at high altitudes?

Answer 21

Concentration increases to promote oxygen release at the tissues

Question 22

What can regulate oxygen binding?

Answer 22

Binding of BPG, H+ and CO2

Question 23

What does the binding of H+ and CO2 do to the affinity of haemoglobin for oxygen?

Answer 23

Decreases affinity

Question 24

What does the Bohr effect ensure?

Answer 24

Ensures the delivery of O2 to tissues is coupled to demand. Metabolically active tissues produce large amounts of H+ and CO2.

Question 25

Why is carbon monoxide poisonous?

Answer 25

CO combines with ferromyoglobin and ferrohaemoglobin, blocking oxygen transport. It also increases the affinity for oxygen for unaffected subunits

Question 26

How much more readily does CO bind to haemoglobin than O2?

Answer 26

250x more readily

Question 27

When is COHb fatal?

Answer 27

> 50%

Question 28

What is the importance of faetal haemoglobin?

Answer 28

Has a higher binding affinity for oxygen than adult haemoglobin which allows transfer of oxygen to foetal blood supply from the mother

Question 29

What is the mutation involved in Sickle Cell Anaemia?

Answer 29

Mutation of Glutamate to Valine in beta globin forming a ‘sticky’ hydrophobic pocket which allows deoxygenated HbS to polymerize.

Question 30

What are sickle cells more prone to?

Answer 30

More prone to lyse - anaemia

Also more rigid - microvasculature

Question 31

What are thalassaemias?

Answer 31

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

Question 32

What are beta-thalassaemias?

Answer 32

Decreased or absent beta globin chain prdouction meaning that alpha chains are unable to form stable tetramers.

Question 33

Do symptoms of beta-thalassaemias appear before or after birth?

Answer 33

After birth

Question 34

What are alpha-thalassaemias?

Answer 34

Decreased or absent alpha-globin chain production. Beta chais can form stable tetramers with increased affinity for oxygen. There can be different levels of severity as there are multiple copies of the alpha chains present.

Question 35

Is alpha-thalassaemia onset before or after birth?

Answer 35

Before birth