Haemoglobin

Question 1

Definition of haemoglobin

Answer 1

Molecule required to efficiently transport O2 from the lungs to respiring tissues

Question 2

Definition of myoglobin

Answer 2

Stored in muscles, unload O2 at very low O2 partial pressures

Question 3

Structure of haemoglobin

Answer 3

2a, 2b chains, 4 haem groups
Haem group has porphyrin ring (Fe2+/Fe3+), make 6 bonds
4 bonds with N, 1 bond with proximal histidine, last spot open for O2
Distal histidine binds to rest of globin

Question 4

Myoglobin structure and properties

Answer 4

Monomeric haem found mainly in muscle
Facilitate O2 transport in rapidly respiring muscle
Receives O2 from Hb

Question 5

Role of distal histidine in haemoglobin

Answer 5

Stabilises O2, déstabilises CO binding by reducing affinity

Question 6

What happens when deoxyhaemoglobin forms

Answer 6

H2O displaces Fe center of haem down by O.4A

Question 7

What happens when oxyhemoglobin forms

Answer 7

O2 binds to Fe center, moves back up into plane

Question 8

Oxygen induced structural arrangements

Answer 8

O2 binds to open space in porphyrin ring, gains e- from Fe2+
Fe3+ has fewer electrons, ionic radius decreases, moves into plane of ring, decreased repulsion
Facilitates allosteric transition from T state to R state, changes affinity for O2 binding to subsequent haems, positive cooperativity

Question 9

Relationship between O2 saturation and PO2 in myoglobin

Answer 9

Typical hyperbolic relationship

O2=PO2/P50 + PO2

Question 10

Relationship between O2 saturation and PO2 in haemoglobin

Answer 10

Sigmoid
+ve cooperative, more binds, easier to bind
Hba is further to the right than Hbf

Question 11

CO2 and H+ transport in Hb in respiring tissues

Answer 11

CO2 + H2O =(carbonic anhydrase)=> HCO3- + H+
Bicarbonate dissolves in plasma, Cl- enters
Decreases affinity for O2

Question 12

CO2 and H+ tranport in Hb in lungs

Answer 12

HCO3- + H+ =(carbonic anhydrase)=> CO2 + H2O
Bicarbonate exerts RBC, Cl- leaves
Increases affinity for O2

Question 13

Bohr effect in tissues

Answer 13

At tissues, lower pH
Curve shifts to the right
Increased binding of CO2
Decreased affinity for O2

Question 14

Opposite of the Bohr effect in lungs

Answer 14

Lungs, higher pH
Curve shifts to the left
Decreased binding of CO2
Increased affinity for O2

Question 15

Structural determinants of Bohr effect

Answer 15

Deoxy => Oxytocin’s, shifts equilibrium between T and R states
Increase in H+ conc favors T state, more O2 released, +ve feedback

Question 16

What is the function of BPG and the effect of the cooperatively curve

Answer 16

Lowers affinity for O2 compared to pure Hb
At altitude, conc of BPG increases, decreases O2 affinity
Curve shifts to the right, more unloaded

Question 17

How does BPG change O2 affinity

Answer 17

T state, favors O2 release
R state, favors O2 pickup
BPG stabilises T state, v lively charged, fits into +ve porphyrin ring
BPG can fit in the central pocket of tetramer

Question 18

BPG and HbF

Answer 18

Made up of 2a, 2y chains
BPG stabilisation is less efficient than Hba
Results in higher O2 binding affinity of Hbf than Hba

Question 19

What causes sickle cell anaemia

Answer 19

Glutamic acid (-ve) substituted by valine (non polar)
Creates hydrophobic sticky patches to normally charged B chains

Question 20

What happens in sickle cell anaemia

Answer 20

When deoxygenated, aggregate into insoluble fibres
Fibres form as valine has a complementary shape to the hydrophobic pocket in chain
Fibres deform RBC into sickle shapes
Cells lyse, carrying capacity of O2 decreases, block up blood vessels

Question 21

Types of haemoglobin present in the embryo

Answer 21

∂2e2
a2e2
∂2y2

Question 22

First haemoglobin present in the embryo

Answer 22

∂2e2

Question 23

Haemoglobin most prevalent at birth

Answer 23

A2y2