Haemoglobin

Question 1

Describe the structure and function of Haemoglobin

Answer 1

It is a tetra heme protein
Found in the erythrocytes (RBC)

Responsible for binding to Oxygen in lines then transporting the bound oxygen throughout the body

Facilitates the return of CO2 from the tissue to the lungs

Overcomes the issue that there is a low O2 solubility

Question 2

Describe the structure and function of Myoglobin

Answer 2

It is a monomeric heme protein found mainly in muscle tissue

Facillitates oxygen transport in rapidly respiring muscle

Mb receives O2 from Hb

Overcomes the issue that there is a low O2 solubility

Question 3

What is the main similarity between Mb and Hb

Answer 3

Both have globular parts

and these parts are very much the same in both molecules

Question 4

Describe the oxygen saturation curve for Hb

Answer 4

Follows a sigmoidal curve- this means that the rate at which O2 binds to Hb is not the same- it changes

Initially the Hb has a low coperativity to oxygen- however Hb exhibits cooperative binding as its affinity for its ligand, oxygen, changes when oxygen is already bound

Low pO2 in the peripheral cells. Hb collects O2 from the high pO2 and transports it to the periphery of lower O2

Question 5

Compare the oxygen saturation curve for HbF and HbA

Answer 5

HbF has a higher affinity for oxygen than HbA- this means that at any pO2 the there will be a greater oxygen saturation with HbF than HbA.

This makes sense because HbF collects O2 from maternal blood supply in the placenta and transports it into the foetus. This can only be possible if HbF binds to oxygen more strongly

Question 6

Describe the quaternary structure of most Hb

Answer 6

dimer of heterodimers

Question 7

Explain how the heme group is incorporated from Hb

Answer 7

Heme is incorporated during synthesis

It is stabilised by hydrophobic residues found in the interior of the protein- prevents the oxidation of Fe2+ to Fe3+

Question 8

Describe the Globin fold

Answer 8

8 alpha helices are connected by turns

Heme binds between E and F ( between proximal His and distal His) These stabilise the binding of O2 to the protein

The distal histidine assists with the stabilising the O2 bound form and destabilising the CO bound form

Question 9

Explain how the structure is rearranged due to O2 inducement

Answer 9

O2 Binding induces Fe ion movement towards the Heme plane
induces the movement of the F helix
facilitating the allosteric change of shape from T-state to R-state

Question 10

What is the Bohr effect

Answer 10

The impact of pH in the binding of O2 onto Hb

1) Oxygen is converted to carbon dioxide in respiring tissue
2) This means that it can be implied that cells with high metabolic activity are releasing lots of CO2
3) CO2 diffuses into blood-

Can dissolve in water- H bonds
Form carbonic acid
Binds covalently to Hb

Question 11

Describe what happens when carbonic acid is produced in blood

Answer 11

When CO2 is released into the blood plasma from respiring tissue
CO2 reacts with water in the erythrocyte to produce bicarbonate ions and protons catalysed by carbonic anhydrase
Bicarbonate dissolves in the blood plasma and chloride enters the RBC (due to the chloride- bicarbonate exchange protein)
This increases the proton yield- which lowers the pH of the blood plasma- this is due to the fact that it binds to numerous binding sites
This decreases pH
This decreases affinity of Hb for O2
O2 is more readily lost- dissociated from Hb

Question 12

Summarise the effects of the Bohr effect

Answer 12

In the peripheral tissues- lower pH means that CO2 and H+ bind- lowering affinity for O2
In the lungs- higher pH due to release of CO2 and H+) increasing the affinity for O2

This is because only deoxy Hb can accept H+ and become deionised

Question 13

What is BPG?

Answer 13

2,3-Biphosphateglycerate

produced metabolically by tissues
allosterically reduces affinity of Hb for O2

BPG binds to the pocket in the centre of the Hb tetramer- but only in the T state. This means that the deoxy state is stabalised
This mean that the T-state is preferred to the R-state
More oxygen is released
Decrease in affinity

Question 14

Describe the effect of BPG on HbF and Hba thus its impact

Answer 14

BPG binds to affinity to HbA with higher affinity- has greater impact on HbA
This means that the affinity for O2 of HbF will be higher

Nb- only on the T state

Question 15

What is sickle cell Anaemia

Answer 15

a genetic disease arisen from the substitution of Glucose to Val on the beta chain on the 6th residue

Question 16

What is the effect of the mutation (SCA)

Answer 16

It creates hydrophobic “sticky” patches on normal charged surfaces of these Beta chains
Upon deoxygenation: the configuration of the HbS differs considerably from HbA as it aggregates into insoluble fibres- these fibres deform the RBCs into sickle shaped cells

RBCs lose their dynamic structure - fixed in a certain structure
This results in the blocking capillaries
Distorting the membrane

Question 17

Clinical Considerations

Answer 17

Low Fe 2+ intake results in anaemia

In merited defects of the haem group gives rise to a variety of Porphyria

Reduced synthesis of alpha and beta chains can result in a group of genetic disorders called thalassemia

Diabetic patients with high levels of glucose in blood-0 increases the amount of glycosylated Hb in red HbA12
Increase in percentage of HbA12 easily measured in blood samples HPLC images or mass spectrometry