FOM 1.4.3

Question 1

What are the basic biological roles of Mb and Hb?

Answer 1

Myoglobin - stores O2 in the muscles Hemoglobin - transports O2 from the lungs to the tissues

Question 2

What amino acids do you expect to be on the surface of myoglobin? Inside?

Answer 2

Hydrophobic on interior and hydrophillic on exterior

Question 3

What is the Quarternary structure of Mb and Hb?

Answer 3

Mb is a monomer and Hb is a tetramer of alpha2 X2

Question 4

How can the tetramer differ for hemoglobin during development?

Answer 4

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

Question 5

What would happen if heme was not surrounded by protein?

Answer 5

Would bind CO 25k times O2 O2 would oxidize the free heme creating Fe3+ which does not bind O2

Question 6

By looking at the binding curve for Hb what are the basic principles that we can determine from it?

Answer 6

It behaves cooperatively It has more than one binding spot

Question 7

How would the O2 binding curve look for myoglobin compared to Hb?

Answer 7

It would be hyperbolic

Question 8

Does Mb or Hb bind O2 tighter? Why?

Answer 8

Mb binds O2 tighter because it needs to be able to take the O2 from the Hb and store it in the tissues

Question 9

What is the O2 binding process in regards to Hb and conformational shifting?

Answer 9

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

Question 10

Does the R or the T state have a higher affinity for O2?

Answer 10

R state

Question 11

Describe the role of BPG in regard to Hb and O2 release?

Answer 11

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

Question 12

What happens to O2 affinity for Hb when BPG is added?

Answer 12

It is reduced greatly and Hb tends release O2

Question 13

What happens to Hb conformational equilibrium when BPG is added?

Answer 13

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.

Question 14

How would the Hb O2 curve look if no BPG was present?

Answer 14

It would be hyperbolic like myoglobin

Question 15

What is a situation that can cause an upregulation of BPG?

Answer 15

Hypoxic conditions can lead to more BPG cause of a need for Hb to release O2

Question 16

What would be a reason for fetal Hb to bind BPG not as well? How is this achieved?

Answer 16

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

Question 17

How are H+ and CO2 involved in allosteric reactions in Hb?

Answer 17

H+ weakens O2 binding at specific site but are unknown CO2 lowers O2 affinity by covalently binding N-terminal amines

Question 18

How would an increase in CO2 shift the curve?

Answer 18

Shift to the right facilitating a release of O2

Question 19

How would an increase in H+ ions shift the curve? Would the O2 affinity be higher or lower?

Answer 19

To the right facilitating release

Question 20

How would Increasing Temp shift the curve?

Answer 20

To the right facilitating release

Question 21

As pH is decreasing what is happening to the concentration of hydrogen ions

Answer 21

They are increasing

Question 22

What role does Mb and Hb have on NO?

Answer 22

Hb and Mb have been known to change NO into nitrate

Question 23

What is the state of Hb in the lungs (a high O2 environment)?

Answer 23

Hb saturated and in high-affinity form BPG is forced to dissociate

Question 24

What happens to Hb in the tissues a lower O2 state the fingers?

Answer 24

O2 dissciates and diffuses into the tissues Hb reverts back to low affinity state BPG binds and facilitates this

Question 25

What is methemoglobinemia?

Answer 25

When Fe2+ is turned to Fe3+ and cannot bind O2 in the heme

Question 26

What was benzocaine’s affect of Hb? How does this affect the O2 binding curve?

Answer 26

It changes the Fe in the heme to 3+. Lowering the amount of overall Hb binding O2. Lowers curve

Question 27

What is a hemoglobinopathy?

Answer 27

A genetic defect that alters the structure of one of the chains

Question 28

What is the antidote for methemoglobinemia?

Answer 28

Methylene blue

Question 29

How does the affinity of CO compare to O2 in regards to binding heme?

Answer 29

CO is much greater than O2

Question 30

How does CO bind Hb and how does it affect it?

Answer 30

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

Question 31

What is thalessemias and what can result from it?

Answer 31

Loss of a subunit. The leftover subunits can aggregate and precipitate damaging the kidneys. Low concentration of normal Hb tetramers results in anemia

Question 32

How can a point mutation affect Hb?

Answer 32

Point mutation can create a wide variety of problems most notably sickle cell anemia

Question 33

What are the defect of Hb Kansas?

Answer 33

Anemia Functional - Normal Bohr decreased cooperativity O2 affinity decreased Unstable protein Rare occurrence

Question 34

What happened to NO in patients that were give Free Hb?

Answer 34

The free Hb scavenged the NO and converted it to nitrate. This caused a large BP spike cause NO is a vasodilator

Question 35

What are the features of an idea Hb substitute?

Answer 35

Limited dioxygenation of NO • Large enough to keep out of smooth muscle with NO • Wild-type O2 binding • Able to withstand blood pressure

Question 36

Describe ways that external, environmental conditions can affect hemoglobin function altitude.

Answer 36

Increased altitude —> decreased pO2 —> decreased saturation of O2-Hb

Question 37

Answer 37

1. It binds cooperatively
2. There are 4 binding events
3. It will look hyperbolic

Question 38

How does pH and CO2 affect the oxygen binding of hemoglobin?

Answer 38

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

Question 39

Explain what would cause a shift in the red line like this in the Hb binding curve

Answer 39

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.

Question 40

Answer 40

A - The shift right shows a decreased affinity with the O2 so that it can be released in the correct tissues.