Hemoglobin Flashcards
Hemoglobin structure
Quaternary
2 alpha 2 beta subunits
What type of structure does myoglobin have
Not quaternary
Only one subunit with one oxygen binding site
Has a globin fold
What does myoglobin do and where is to
In the muscle
Transports oxygen
How do myoglobin and hemoglobin transport oxygen
Through use of heme groups
What is the structure of heme groups
There an fe2+ ion attached to four surrounding nitrogen’s from four pyrrole rings
Since fe 2+ it can form two extra bonds on each side of the heme plane (5th and 6th coordination sites)
What are the 5th and 6th coordination site of the heme group
5th: it’s occupied by the proximal histidine that attached to the fe on the bottom of the heme group
6th: it is at the top of the heme group that is available for oxygen to bind
What happens when oxygen binds to the 6th coordination site
Since the iron with just the 5 site with his occupied is 0.4 A below the heme ring
That addition of the o2 to the top of the ring pulls the iron up 0.4 A into the ring by making it smaller (due to movement of electrons)
What type of way does oxygen bing to hemoglobin
Cooperatively
Give a Sigmoidal curve
This means that when oxygen bind to a spot on hemoglobin it’s much more likely than myoglobin that another oxygen will bind
What is the partial pressure of o2 in the lungs
In tissues
100 torr
20
O2 transport from the lungs to the tissues
How does cooperativity actually affect the delivery of oxygen
For hemoglobin that does cooperative, the delivery of oxygen to the tissues is 66% (66% of binding sites released oxygen)
But for myoglobin that isn’t cooperative, only 7% of the oxygen binding site release oxygen into the tissues
This means that cooperative binding enhance the delivery of oxygen
If oxygen is bonded what state is the hemoglobin in
If oxygen is not bound
R state (smaller cavity in the middle of the protien)
T state
How does the binding of oxygen change whether the protien is in the t or r state
The binding of the oxygen shifts the proximal histidine (which move the iron up 0.4A)
This also results in the alpha helix attached to the histidine moving
This change the interface of the alpha beta dimer and changes the conformation to R
How can the hemoglobin be regulated allosterically
It can be regulated by a negatively charged molecule called 2,3 BPG
The 2,3 BPG binds to a pocket that’s only present on depxygemoglobin (t state) and stabilizers (keeps) it in that state
This allows for more oxygen to be released from the hemoglobin (66%)
Once 2,3 BPG is attached to the hemoglobin how do the hemoglobin go back to the R state
The 2,3 BPG must be expelled
How does 2,3 BPG actually stablize the structure of the T state
It binds to the central cavity of deoxyhemoglobin and interacts with positively charge HIS residues since it’s negatively charged
Decreasing the affinity for 2,3 BPG will
Increase the affinity for oxygen
Why does fetal hemoglobin have a higher affinity for oxygen
The fetal hemoglobin has 2 aplha and two GAMMA chains (not beta)
These gamma chains are 72%i dentical to the beta chains but the positive his residues that interact with BPG turn to serine
This decreased the affinity for BPG THUS increasing oxygen affinity
The affinity of oxygen for fetal hemoglobin must be _____ compared to maternal hemoglobin
Higher so the the oxygen from material is released and given to fetal
What is the Bohr effect
When H and CO2 regulate the binding of oxygen to hemoglobin
What is the affect of a decrease in PH
More release of oxygen
This is because a salt bridge gets formed and stabilizers the t (deoxy) state of hemoglobin since his 146 is protonated
Drop to ph 7.2 leads to 77% of oxygen binding site to realese oxygen at the tissures
What is the affect of an increase in PH
The his 146 is deprotonated and this disrupts the salt bridge formation (no more t state deoxy) so this favours o2 to bind and not be released
How does co2 promotes the release of o2
The co2 reacts with the terminal amino groups in hemoglobin to form carbamate (negatively charged)
The carbamate groups form salt bridges at the interface of alpha beta dimers (t state, deoxy)
This decreases the affinity for oxygen
What are the three allosteric regulators of hemoglobin
BPG
PH
CO2
What is sickle cell anemia
Both copies of the hemoglobin gene are mutated
Misstated Sickle cell hemoglobin forms fibres that deform the cell and the cell ruptures easily, leading to anemia
What exactly is the sickle cell mutation and what does it do
A glu 6 to Val 6 mutation in beta chains
The mutation decreases the solubility of the t form (deoxy) hemoglobin but not the R form (oxy)
This means that when there’s a high concentration of deoxyhemoglobin the Val 6 interact with PHE 85 and leu 88 (sticky patches) to make aggregates of hemoglobin
This forms the fibres that deform the cell
Whats a potential treatment for hemoglobin disorders
Take blood stem cells from patient
Edit it to remove the fetal hemoglobin suppressor
Inject these back into patient
This makes normal red blood cells
