15 - Oxygen Transport Flashcards
What is the structure of haemoglobin?
- Quaternary structure
- 4 subunits, 2a 2b, tetrameric
- Each polypeptide chain has haem prosthetic group
- Each chain similar to myoglobin
What is the structure of the haem group?
- Porphyrin planar ring with Fe in the middle
- Free haem, Fe can make two bonds, one above and one below ring
- Forms bond with histidine residue (proximal histidine) from protein, and one molecule of O2
What does it mean by prosthetic route in haem?
When Fe is bound to a histidine residue and one O2 rather than two O2’s
What is the structure of myoglobin?
- Tertiary structure
- 1 subunit
- Mainly alpha helices (no beta)
- Compact (globular)
- Small
- His 93 in 8th alpha helix is covalently linked to Fe
What happens to the shape of myoglobin when oxygen binds?
- Fe is below the planar ring in deoxymyoglobin
- When oxygen binds this causes movement of Fe into the plane of the ring, causing Histidine to move up so very small change in protein conformation when histidine moves
- Not enough change to notice
What does the binding curve of myoglobin look like?
What does the haemoglobin binding curve look like?
What are the two states of haemoglobin?
T (tense) state: low affinity state, no o2 bound
R (relaxed) state: high affinity state, o2 bound
When O2 is bound it promotes stabilisation of the R state
What is the cooperative binding of oxygen?
As oxygen binds to haemoglobin, there is a conformational change in haemoglobin and this causes haemoglobin to have a higher affinity for O2
BINDING AFFINITY INCREASES AS MORE O2 BINDS
How does binding of oxygen to haemoglobin cause a change in conformation
Histidine pulling
Why is the cooperative effect important?
So oxygen binds at high partial pressure of oxygen and dissociates at low partial pressures of oxygen
What are the three ways oxygen binding is regulated?
1. 2,3-BPG (2,3 bisphosphate glycerate)
2. CO2 and H+
3. Carbon monoxide
What does 2-3 BPG do?
- Allosterically binds to haemoglobin, stabilising the T form
- Binds to positives on B-subunits
- Decreases affinity for O2 and shifts curve to the right
- In RBC at 5mM
How does 2,3-BPG concentration vary?
- In highly metabolic tissues high BPG
- At high altitudes more BPG produced
- More BPG promotes oxygen release into tissues
What is the Bohr effect?
- An increase in PCO2 OR a decrease in pH, causes a Hb to have a decrease in affinity for O2, curve shift to right
- Allosteric binding
- High metabolic tissues produce lots of H+ and CO2 so ensures oxygen release into tissue so supply can meet demand