Hemoglobin And Transport Of Respiratory Gases

Question 1

Explain the biochemical basis of Haemoglobin as a gas transporter

Answer 1

1. Hb transports oxygen from lungs to tissues & carbondioxide from blood to lungs
2. Hb is a haem protein made in erythroblasts & reticulocytes
3. A tetramer (4 globin chains + 4 haem proteins)
4. Hb has 4 subunits: 2 Alpha chains & 2 Beta chains ⛓️⛓️
5. Allows reversible binding of oxygen with haem, due to hydrophobic pocket formed by globin chain (to protect Fe2+ state)
6. Prevents oxidation of Fe2+ → Fe3+ (needed because only Fe2+ state of iron is able to bind to oxygen)
7. Ham group has Fe2+ & protoporphyrin ring (4 pyrol rings with N)
8. Fe2+ can form 6 bonds: 4 with N of pyrol ring; 1 with oxygen; 1 to proximal histidine residue
9. 2 forms of Hb: T state & R state
10. T state (deoxy form) has low affinity for oxygen & restricted movement of polypeptide chain
11. R state (oxy form) has high affinity for oxygen & allows movement of polypeptide chain
12. As Hb contains multiple subunits, it can exhibit allostery
13. In Hb, oxygen is both a ligand & an effector
14. Binding of 1 oxygen molecule increases the binding affinity of the remaining subunits (co-operativity)
15. Co-operative binding of oxygen allows Hb to deliver more oxygen to tissues in response to small changes in PO2
16. These structural features of Hb are important for it to be an efficient gas transporter
17. Histidine molecules in Hb are responsible for the buffering action (to maintain blood pH)

Question 2

Biochemical basis of Bohr’s effect

Answer 2

1. ↑ Carbon dioxide @ tissues so it diffuses into RBCs
2. Carbon dioxide is needed for carbonic acid which dissociates into H+ & HCO3-
3. H+ binds to oxyhaemoglobin which is an unstable complex
4. It dissociates & releases oxygen @ tissues

Question 3

Why is HbF not suitable for post natal life?

Answer 3

1. HbF is the main oxygen transport in foetus (2 alpha globin chains + 2 gamma globin chains)
2. Gradually replaced by HbA (2 alpha chains + 2 beta chains)
3. Foetal Hb cannot bind 2,3 - BPG tightly (as gamma subunit of HbF has ↓ positive charges than beta subunit of HbA)
4. • charges are responsible for binding 2,3 - BPG
5. So 2,3 - BPG can bind only weakly to HbF (normally 2,3 - BPG stabilizes the taut state & reduces oxygen affinity of Hb)
6. Since HbF only weakly binds, Hb is in the relaxed state & oxygen affinity of HbF is ↑ed
7. In adult life, Hb must be able to reversibly bind to oxygen; be able to bind oxygen when PaO2 is ↑; release oxygen when PaO2 is ↓
8. Due to ↑ affinity of HbF to oxygen, ↓ oxygen is released to tissues so it is insufficient to maintain all vital functions after birth and leads to tissue hypoxia