Lecture 17 - Hemoglobin and Myoglobin

Question 1

Describe the differences between myoglobin and hemoglobin

Answer 1

myoglobin: monomer, binds 1 O2 molecule, in muscle cells, used for oxygen storage, unaffected by pH, [CO2], and BPG
Hemoglobin: tetramer, binds 4 O2 molecules, in RBCs, used for oxygen transport, affected by pH, [CO2], and BPG

Question 2

Describe the heme group

Answer 2

iron 2+ ion within tetrapyrrole ring (protoporphyrin IX)

Question 3

Describe cooperative binding

Answer 3

Iron is octahedral shape, has 4 bonds to tetrapyrrole ring, 1 bond to oxygen, one bond to His F8. Oxygen is bound to iron and His E7. When oxygen binds, it pulls iron into plane of the heme group, pulls F helix as well. This causes a narrowing of the central cavity, and drastically increases the affinity for oxygen of the other two heme groups.
Changes from tense to relaxed state

Question 4

How does BPG affect binding affinity?

Answer 4

Stabilizes the T state, binds in the central pocket b/c highly negative. Makes hemoglobin more efficient at unloading O2 at the tissues because it is less likely to rebind to O2

Question 5

How does fetal hemoglobin differ from adult hemoglobin

Answer 5

Has His143 substituted for a serine, removes positive charges, and lowers affinity for BPG, therefore increasing O2 affinity

Question 6

How does pH and CO2 affect binding affinity

Answer 6

As pH is lowered, salt bridges in T state reinforced so T state stabilized. CO2 reacts to produce HCO3 and H so again stabilizes T state and salt bridges.

Question 7

What is the amino acid change that results in sickle cell anemia?

Answer 7

Glu6 –> Val