Haemoglobin

Question 1

Why is O2 a key component of ATP generation?

Answer 1

It is the final electron acceptor in oxidative phosphorylation

Question 2

Where is O2 stored?

Answer 2

In striated muscles bound to myoglobin

Question 3

Features of Hb

Answer 3

Tetramer - made of 2 beta globin subunits and 2 identical alpha globin subunits
It is a dimer of a dimer

Question 4

Features of Mb

Answer 4

Monomer

Question 5

Similarities in Hb and Mb structures

Answer 5

~150 amino acids long
Include haem group in a hydrophobic pocket
Hydrophilic side of haem group faces the surface of the globin
Each haem group can bind O2

Question 6

Haem group

Answer 6

Fe2+ can bond with 6 ligands
Exists in 2 forms - oxyhaemoglobin and deoxyhaemoglobin
Haem with Fe3+ is unable to bind to O2

Question 7

6 ligands that Fe2+ can bind to

Answer 7

4 by Nitrogen atoms of haem group
5th by attachment to specific histidine of globin
6th is available for reversible attachment of oxygen

Question 8

What prevents Fe2+ from being oxidised to Fe3+?

Answer 8

Hydrophobic residues found in the interior of globin

Question 9

What is cooperative oxygen binding?

Answer 9

Increase in affinity of Hb for oxygen as the occupancy for Hb increases
Example of allostery

Question 10

What is allostery?

Answer 10

When the binding of oxygen to one globin changes the shape of the binding site of another globin

Question 11

What is the tense state of haemoglobin?

Answer 11

Low affinity for O2

Question 12

What is the relaxed state of haemoglobin?

Answer 12

High affinity for O2

Question 13

How is CO2 transported in the blood?

Answer 13

Some dissolved in the blood
Most converted to carbonic acid, which dissociates to bicarbonate
Some CO2 reversibly binds to Hb to form carbaminohaemoglobin

Question 14

Bohr effect

Answer 14

Ability of haemoglobin to bind oxygen decreases as the [H+] increases (due to CO2 production)

Question 15

Why does [H+] affect binding of O2 to haemoglobin?

Answer 15

In order to be transported, CO2 is converted into H2CO3
pKa of carbonic acid is 6.4 and at physiological pH, it dissociates into H+ and HCO3-
Increase in [H+] causes Hb to release O2

Question 16

BPG and Oxygen binding of haemoglobin

Answer 16

2,3 bisphosphate is allosteric regulator of oxygen binding of haemoglobin
BPG is generated by metabolising tissues
BPG binds to internal position of Hb in the tense state
BPG is negatively charged and binds to positively charged pocket
Binding of BPG lowers the affinity of Hb for oxygen
Without BPG, oxygen binding curve of HbA is similar to Mb

Question 17

Difference between affinity of HbF and HbA

Answer 17

HbF has variation in sequence causing less BPG binding
HbF has greater affinity for Oxygen than HbA

Question 18

Sickle cell anaemia

Answer 18

Recessively inherited disease
Mutation of beta globin
Sticky hydrophobic patches on normally charged surface of the beta globin

Question 19

HbS aggregation

Answer 19

Conformational change in deoxy Hb causes alpha helix containing position 6 shifting to position more on the surface
In HbS to prevent valine being in an aqueous environment two haemoglobin molecules aggregate together
This aggregation continues to form polymers

Question 20

How many oxygen molecules bind to MetHb when fully saturated?

Answer 20

0
Met Hb contains Fe3+, which cannot bind to oxygen

Question 21

Subunit structure of HbF

Answer 21

α2 γ2