FOM 1.4.3 Flashcards
What are the basic biological roles of Mb and Hb?
Myoglobin - stores O2 in the muscles Hemoglobin - transports O2 from the lungs to the tissues
What amino acids do you expect to be on the surface of myoglobin? Inside?
Hydrophobic on interior and hydrophillic on exterior
What is the Quarternary structure of Mb and Hb?
Mb is a monomer and Hb is a tetramer of alpha2 X2
How can the tetramer differ for hemoglobin during development?
Alpha subunits will always remain the same, but the other two will change as growth occurs due to changes in needs of the person. Adult vs fetal vs minor
What would happen if heme was not surrounded by protein?
Would bind CO 25k times O2 O2 would oxidize the free heme creating Fe3+ which does not bind O2
By looking at the binding curve for Hb what are the basic principles that we can determine from it?
It behaves cooperatively It has more than one binding spot
How would the O2 binding curve look for myoglobin compared to Hb?
It would be hyperbolic
Does Mb or Hb bind O2 tighter? Why?
Mb binds O2 tighter because it needs to be able to take the O2 from the Hb and store it in the tissues
What is the O2 binding process in regards to Hb and conformational shifting?
Binding O2 causes Hb to shift in to a higher affinity state for O2 and even higher for subsequent O2 molecules known as R state
Does the R or the T state have a higher affinity for O2?
R state
Describe the role of BPG in regard to Hb and O2 release?
BPG binds in the center of Hb in the low-affinity state to ensure the Hb does not pick up O2 in the tissues. BPG does not bind in the high affinity form
What happens to O2 affinity for Hb when BPG is added?
It is reduced greatly and Hb tends release O2
What happens to Hb conformational equilibrium when BPG is added?
BPG shifts the equilibrium towards DeoxyHb-BPG from DeoxyHb. This causes OxyHb to release O2 in order to compensate for the lost DeoxyHb. BPG facilitates the conformational change to deoxyHb.
How would the Hb O2 curve look if no BPG was present?
It would be hyperbolic like myoglobin
What is a situation that can cause an upregulation of BPG?
Hypoxic conditions can lead to more BPG cause of a need for Hb to release O2
What would be a reason for fetal Hb to bind BPG not as well? How is this achieved?
Fetal Hb needs to be able to get O2 from the mother so fetal Hb has a higher affinity for O2. BPG does not bind as well because Serine residues with hydroxyl side chains are in the binding site and BPG wont bind as well
How are H+ and CO2 involved in allosteric reactions in Hb?
H+ weakens O2 binding at specific site but are unknown CO2 lowers O2 affinity by covalently binding N-terminal amines
How would an increase in CO2 shift the curve?
Shift to the right facilitating a release of O2
How would an increase in H+ ions shift the curve? Would the O2 affinity be higher or lower?
To the right facilitating release
How would Increasing Temp shift the curve?
To the right facilitating release
As pH is decreasing what is happening to the concentration of hydrogen ions
They are increasing
What role does Mb and Hb have on NO?
Hb and Mb have been known to change NO into nitrate
What is the state of Hb in the lungs (a high O2 environment)?
Hb saturated and in high-affinity form BPG is forced to dissociate
What happens to Hb in the tissues a lower O2 state the fingers?
O2 dissciates and diffuses into the tissues Hb reverts back to low affinity state BPG binds and facilitates this
What is methemoglobinemia?
When Fe2+ is turned to Fe3+ and cannot bind O2 in the heme
What was benzocaine’s affect of Hb? How does this affect the O2 binding curve?
It changes the Fe in the heme to 3+. Lowering the amount of overall Hb binding O2. Lowers curve
What is a hemoglobinopathy?
A genetic defect that alters the structure of one of the chains
What is the antidote for methemoglobinemia?
Methylene blue
How does the affinity of CO compare to O2 in regards to binding heme?
CO is much greater than O2
How does CO bind Hb and how does it affect it?
CO bind in one spot on the Hb. It then stays in that spot and keeps Hb in the high affinity state. So that Hb picks up O2 but does not release it when at the tissues
What is thalessemias and what can result from it?
Loss of a subunit. The leftover subunits can aggregate and precipitate damaging the kidneys. Low concentration of normal Hb tetramers results in anemia
How can a point mutation affect Hb?
Point mutation can create a wide variety of problems most notably sickle cell anemia
What are the defect of Hb Kansas?
Anemia Functional - Normal Bohr decreased cooperativity O2 affinity decreased Unstable protein Rare occurrence
What happened to NO in patients that were give Free Hb?
The free Hb scavenged the NO and converted it to nitrate. This caused a large BP spike cause NO is a vasodilator
What are the features of an idea Hb substitute?
Limited dioxygenation of NO • Large enough to keep out of smooth muscle with NO • Wild-type O2 binding • Able to withstand blood pressure
Describe ways that external, environmental conditions can affect hemoglobin function altitude.
Increased altitude —> decreased pO2 —> decreased saturation of O2-Hb
- It binds cooperatively
- There are 4 binding events
- It will look hyperbolic
How does pH and CO2 affect the oxygen binding of hemoglobin?
A lower pH means that there is more H+ ions, thus shifting the curve to the right (higher pO2) and having a lower affinity for O2.
CO2 lowers O2 affinity by covalently bind the N-terminal
Explain what would cause a shift in the red line like this in the Hb binding curve
Some chemicals in nature do this. They bind to hemoglobin irreversibly, and do not allow the hemoglobin to release the O2. It lowers the amount of Hb to be used and thus has a lowered line. Can also have a line shift to the left as in CO poisoning.
A - The shift right shows a decreased affinity with the O2 so that it can be released in the correct tissues.
