Hemoglobin

Question 1

Hemoglobin structure

Answer 1

Quaternary

2 alpha 2 beta subunits

Question 2

What type of structure does myoglobin have

Answer 2

Not quaternary

Only one subunit with one oxygen binding site

Has a globin fold

Question 3

What does myoglobin do and where is to

Answer 3

In the muscle

Transports oxygen

Question 4

How do myoglobin and hemoglobin transport oxygen

Answer 4

Through use of heme groups

Question 5

What is the structure of heme groups

Answer 5

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)

Question 6

What are the 5th and 6th coordination site of the heme group

Answer 6

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

Question 7

What happens when oxygen binds to the 6th coordination site

Answer 7

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)

Question 8

What type of way does oxygen bing to hemoglobin

Answer 8

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

Question 9

What is the partial pressure of o2 in the lungs

In tissues

Answer 9

100 torr

20

O2 transport from the lungs to the tissues

Question 10

How does cooperativity actually affect the delivery of oxygen

Answer 10

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

Question 11

If oxygen is bonded what state is the hemoglobin in

If oxygen is not bound

Answer 11

R state (smaller cavity in the middle of the protien)

T state

Question 12

How does the binding of oxygen change whether the protien is in the t or r state

Answer 12

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

Question 13

How can the hemoglobin be regulated allosterically

Answer 13

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%)

Question 14

Once 2,3 BPG is attached to the hemoglobin how do the hemoglobin go back to the R state

Answer 14

The 2,3 BPG must be expelled

Question 15

How does 2,3 BPG actually stablize the structure of the T state

Answer 15

It binds to the central cavity of deoxyhemoglobin and interacts with positively charge HIS residues since it’s negatively charged

Question 16

Decreasing the affinity for 2,3 BPG will

Answer 16

Increase the affinity for oxygen

Question 17

Why does fetal hemoglobin have a higher affinity for oxygen

Answer 17

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

Question 18

The affinity of oxygen for fetal hemoglobin must be _____ compared to maternal hemoglobin

Answer 18

Higher so the the oxygen from material is released and given to fetal

Question 19

What is the Bohr effect

Answer 19

When H and CO2 regulate the binding of oxygen to hemoglobin

Question 20

What is the affect of a decrease in PH

Answer 20

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

Question 21

What is the affect of an increase in PH

Answer 21

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

Question 22

How does co2 promotes the release of o2

Answer 22

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

Question 23

What are the three allosteric regulators of hemoglobin

Answer 23

BPG

PH

CO2

Question 24

What is sickle cell anemia

Answer 24

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

Question 25

What exactly is the sickle cell mutation and what does it do

Answer 25

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

Question 26

Whats a potential treatment for hemoglobin disorders

Answer 26

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