Haemoglobin Flashcards
What is the Bohr effect?
A right shift in the oxygen dissociation curve for increases in PCO2, D-2,3 BPG and decreases in pH, as oxygens affinity for Hb decreases
What is the structure of the heme group found within each chain of the Hb tetramer?
It is Fe2+ surrounded by a porphyrin ring
What is the structure of the globin fold?
X8 alpha helices names A - H
Between which alpha helices does heme bind?
Which residues specifically are involved in the heme binding?
Between helices E and F
Histidine residues
Between which X2 specific histidine residues does heme bind?
The distal histidine = helix E7 (His 64)
The proximal histidine = helix F8 (His 93)
NB: distal histidine = 7th residue in the E helix and 64th in the chain overall from the N-terminus end
How many co-ordination sites does Fe2+ have?
What is each bound to?
X6
X4 connects it to the porphyrin ring
X1 to the proximal histidine
X1 is free to bind O2
If the distal histidine is not involved in bonding heme, what does it do?
Stabilises O2 when it is bound to the Iron
Where does Fe2+ sit with respect to the heme plane and why?
What happens when oxygen binds?
0.4A (angstrom) below it due to its larger ionic radius.
When oxygen binds it reduced in radius as electrons flow (partially) from Fe2+ —> O2 which moves the Fe molecule above the heme plane.
What does the O2 induced structural rearrangement allow for and how?
It allows for positive co-operability.
As the Fe moves above the heme plan it takes the attaches proximal histidine residue with it which is part of the F alpha helix. There is an overal structural rearrangement in Hb quaternary structure and less contact between the alpha and beta subunits.
What are the states of deoxy and oxyhaemoglobin?
T state = tense state = deoxy Hb
R state = relaxed state = oxy Hb
What happens as pH decreases to shift the Bohr curve to the right and decrease the affinity of O2 for Hb?
As pH drops, histidine 146 side chain is protonated which forms a bond with aspartate 94 which stabilises the T-state deoxyhaemoglobin, promoting O2 release.
What happens to shift the Bohr curve right at altitude?
At altitude 2,3 BPG increases.
This binds to the central Hb cavity ONLY in T-state Hb, promoting this state and therefore decreased O2 affinity for Hb.
What happens to cause sickle cell anaemia?
A mutation in the beta chain causes glutamate to turn to valine at position 6, which sits outside of the molecule.
This creates a non-polar region (as glutamate is polar, but valine is not).
This interacts with other Hb regions of valine and to overcome this they form insolvable fibre like strands which deform the RBC’s into a sickle-like shape.
