Chapter 9- Hemoglobin

Question 1

Hemoglobin traits/function

Answer 1

• allosteric protein
• component of red blood cells
• carries oxygen from the blood to the tissues
• transports co2 & hydrogen ions back to lungs
• displays cooperative behavior (marked Sigmoidal)

Question 2

Heme

Answer 2

• Prosthetic group
• Enables hemoglobin & myoglobin to bind oxygen
• Gives muscle & blood their distinct red color
• consists of an organic component called protoporphyrin, the iron atom lies in the center bonded to the 4 pyrrole nitrogen atoms
• under normal conditions iron is in the ferrous Fe2+ state
• the distal histidine prevents the oxidation of the heme iron to the ferric ion Fe3+ which cannot bind to oxygen

Question 3

Quaternary structure

Answer 3

Like all allosteric proteins, hemoglobin displays quarter art structure

-hemoglobin A, present in adults, consists of 4 subunits: two alpha, two beta. They are similar to that of myoglobin. (A1b1, a2b2)

• deoxy corresponds to the T state
• oxy corresponds to the R state

Question 4

What accounts for the difference between purified hemoglobin and hemoglobin in red blood cells?

Answer 4

The dramatic difference is due to the presence of an allosteric regulator molecule–2,3-biphosphoglycerate aka 2,3-BPG or 2,3-DPG

It binds to hemoglobin reducing its affinity for oxygen so that 66% of the oxygen is released instead of a mere 8%.

*Cool: fetal hemoglobin exhibits reduced affinity for 2,3-BPG so that it has a higher affinity for oxygen to survive

Question 5

Hemoglobin S

Answer 5

Sickle-cell hemoglobin

• Africans: Malaria resistance
• the blood cells have bound together to form large fibrous aggregates that give them their shape (hydrophobic patch)
• it differs from Hb A in a single amino acid substitution of valine for glutamate at position 6 of the beta chains.
• this mutation places nonpolar valine on the outside of the hemoglobin S which reduces the solubility of the deoxygenated but not the oxygenated form of hemoglobin–high concentration of deoxygenated form.

Question 6

Bohr Effect: pH (hydrogen ions)

Answer 6

The regulation of oxygen binding by hydrogen ions and carbon dioxide

-CO2 inside tissues diffuse into red blood cells. Inside, it reacts with water to form carbonic acid (catalyzed by carbonic anhydrase). Carbonic acid dissociates to form HC03- and H+, resulting in a drop in pH inside the red cell. 7.4 to 7.2 which in turn releases 77% oxygen instead of 66%. This is due to side chain of histidine becoming pronated & forming a salt bridge w aspartate

Question 7

Bohr effect: Carbon dioxide

Answer 7

In addition, hemoglobin responds to carbon dioxide wth an amount reaching 90% of maximum carrying capacity at pH 7.2

-carbon dioxide stabilizes deoxy by reacting with terminal amino groups to form carbamate groups which are negatively charged. These then participate in salt bridges characteristic of the T state structure which favors the release of oxygen. Thus, regulation of hemoglobin further increase efficiency of this magnificent allosteric protein.

Question 8

What is they physiological significance of cooperative binding of oxygen to hemoglobin?

Answer 8

The transition of iron ion to the other subunits brings changes in the quaternary structure with a change of about 15 degrees in the alpha beta diners. This facilitates communication between the dimers.

The cooperative binding facilitates more amount of oxygen to be carried to tissues increasing efficiency of oxygen transport.

Question 9

Describe be the role of 2,3-BPG in the function of hemoglobin

Answer 9

The binding of 2,3-BPG decreases oxygen affinity

-this prevents hypoxia conditions in higher altitudes where oxygen levels are low. A body in such conditions produces excess BPG so that more oxygen is released into the tissues