S14 Protein Function - Oxygen Transport

Question 1

Why is the structure of haem as it is?

Answer 1

To allow oxygen to bind

Question 2

How is the Fe atom bound to Hb?

Answer 2

Bound via a histidine residue on the side of the ring

Question 3

Is myoglobin large or small?

Answer 3

Small (153 amino acids (100 or more classes as a protein))

Question 4

What does binding of oxygen mean happens to the plane in myoglobin?

Answer 4

Oxygen binding causes movement of Fe into the plane of the ring (causes a small change in protein conformation that has no major effects)

Question 5

What type of curve is seen with oxygen binding to myoglobin?

Answer 5

Hyperbolic

Question 6

What type of curve is seen with oxygen binding to Hb?

Answer 6

Sigmoidal

Question 7

How many polypeptide chains is Hb made up of?

What about myoglobin?

Answer 7

2

1

Question 8

What are the two states of Hb?

Answer 8

T - low affinity state

R - high affinity state

Question 9

Which state does oxygen binding promote the stabilisation of?

Answer 9

The R state

Question 10

What does binding of 2,3-BPG do to Hb?

Answer 10

Decreases Hb affinity of oxygen

BPG conc increases at high altitudes, promotes oxygen release at the tissues

Question 11

What does binding of carbon dioxide and H+ do to Hb affinity for oxygen? What is its significance?

Answer 11

Lower the affinity (Bohr effect)

H+ and CO2 produced by metabolically active tissues - the Bohr affect means that delivery of O2 is coupled with demand

Question 12

What is the affect of carbon monoxide poisoning on Hb?

Answer 12

Binds to the Fe in Hb (ferroHb) and blocks oxygen transport as CO can bind more readily than O2

Question 13

What are the polypeptide chains in HbA, HbF and HBA2?

Answer 13

HbA - alpha 2 and beta 2
HbF - alpha 2 and gamma 2
HbA2 - alpha 2 and delta 2

Question 14

What is the most common Hb in human adults?

Answer 14

HbA (90%)

Question 15

What is the importance of foetal Hb (HbF)?

Answer 15

It is the major Hb in foetal blood

It has a higher binding affinity for oxygen than HbA which allows transfer of oxygen to the foetal blood supply from the mother

Question 16

Which direction does the curve shift for increased affinity?

Answer 16

To the left

Question 17

What mutation causes sickle cell anaemia?

Answer 17

Mutation of glutamate to valine in the beta globin (HbS)

Question 18

What does the mutation Glu —> Val cause in Hb?

Answer 18

A sticky hydrophobic pocket (Val is hydrophobic, Glu isn’t) which allows HbS to polymerise.

Question 19

What are sickled cells prone to? What is their structure?

Answer 19

More prone to lyse

More rigid (block microvasculature e.g. capillaries)

Question 20

What are thalassaemias?

Answer 20

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

Question 21

What is beta-thalassaemia? What form of Hb takes over?

Answer 21

• decreased/absent beta-globin chain production
• alpha chains unable to form stable tetramers
• symptoms appear after birth

(Major is both beta globins missing, minor is only one missing)

HbF takes over (not ideal in high amounts)

Question 22

What is alpha-thalassaemia?

Answer 22

• decreased or absent alpha globin chain production
• different levels of severity due to multiple copies of the alpha chains present (alpha 1 and alpha 2)
• beta chains can form stable tetramers with increased affinity for oxygen
• onset before birth

Question 23

What are the different levels of severity for alpha thalassaemia?

Answer 23

1. Normal - 2 alpha-1, 2 alpha-2
2. Silent carrier - 1 alpha-1, 2 alpha-2
3. Alpha-thalassaemia trait (heterozygous clinically mild) - no alpha-1, 2 alpha-2
4. Alpha-thalassaemia trait (heterozygous clinically mild) - 1 alpha-1, 1 alpha-2
5. HbH disease (clinically severe) - 1 alpha-2
6. Hydrops fetalis (fatal after birth) - none

Question 24

How many haem subunits make up HbA?

Answer 24

4 haem containing subunits - 2 alpha, 2 beta