Chapter 9: Hemoglobin - An allosteric protein

Question 1

Define: Myoglobin

Answer 1

Displays tertiary structure only

Question 2

Define: Heme

Answer 2

Oxygen-binding component of hemoglobin and myoglobin

Question 3

Define: Protoporphyrin

Answer 3

Composed of four pyrrole rings

Question 4

Define: Proximal Histidine

Answer 4

Binds the fifth coordination site in the heme

Question 5

Define: 2,3-Bisphoshphoglycerate

Answer 5

Binds in the center of the hemoglobin tetramer

Question 6

Define: Sickle-Cell Anemia

Answer 6

Results from the change of a single amino acid in the B-chain of hemoglobin

Question 7

Define: Bohr Effect

Answer 7

The regulation of oxygen binding by hydrogen ions and carbon dioxide

Question 8

Define: Carbonic Anhydrade

Answer 8

Facilitates the formation of protons and bicarbonate

Question 9

Define: Carbamate

Answer 9

Amino termini structures that stabilize the T state

Question 10

What is the physiological significance of the cooperative binding of oxygen by hemoglobin?

Answer 10

The cooperatively allows hemoglobin to become saturated in the lungs, where oxygen pressure is high.

When the hemoglobin moves to tissues, the lower oxygen pressure induces it to release oxygen and thus deliver oxygen where it is needed.

Thus, the cooperative release favors a more complete unloading of oxygen in the tissues.

Question 11

What accounts for the fact that feral hemoglobin has a higher oxygen affinity than maternal hemoglobin?

Answer 11

Fetal hemoglobin does not bind 2,3-BPG as well as maternal hemoglobin does.

Question 12

How does hemoglobin S cause tissue damage?

Answer 12

Hemoglobin S molecules bind together to form large fibrous aggregates that extend across the cell, deforming the red blood cells and giving them their sickle shape.

This aggregation takes place predominately in the deoxygenated form of the Hb S.

Small blood vessels are blocked because of the deformed cells, which creates a region of low oxygen concentration. Hence, more hemoglobin changes into the deoxy form and so more cells undergo sickling.

Sickled red cells become trapped in the small blood vessels, impairing circulation and leading to the damage of many tissues. Sickled cells, which are more fragile than normal red blood cells, rupture readily to produce serve anemia.

Question 13

Describe the role of 2,3-bisphosphoglycerate in the function of hemoglobin.

Answer 13

The presence of 2,3-BPG shifts the equilibrium toward the T state. 2,3-BPG binds only to the center cavity of deoxy hemoglobin (T state).

The size of the center cavity decreases on the change to the R form, expelling the 2,3-BPG and thus facilitating the formation of the R-state.

Question 14

After a person spends a day or more at high altitude (with an oxygen partial pressure of 75 torr), the concentration of 2,3-diphosphoglycerate in that person’s red blood cells increases.

What effect would an increased concentration of 2,3-BPG have on the oxygen-binding curve for hemoglobin?

Explain why this adaptation would be beneficial for functioning well at high altitude.

Answer 14

A high concentration of 2,3-BPG would shift the oxygen-binding curve to the right.

The rightward shift of the oxygen-binding curve would promote the dissociation of oxygen in the tissues and would thereby increase the percentage of oxygen delivered to the tissues.

Question 15

What is the Bohr Effect, and what is the chemical basis?

Answer 15

The Bohr Effect is the regulation of hemoglobin oxygen binding by hydrogen ions and carbon dioxide.

Deoxyhemoglobin is stabilized by ionic bonds that stabilize the T state. One of these bonds forms between the carbonyl-terminal His B146 and Asp B94.

As the pH increases, this stabilizing salt bridge is broken because His B146 becomes deprotonated and loses its positive charge, facilitating the formation of the R state. At lower pH values, His B146 is positively charged.

The formation of the ionic bonds shifts the equilibrium from the R state to the T state, thus releasing oxygen.

Question 16

The pKa of an acid depends partly on its environment. Predict the effect of the following environmental changes on the pKa of s glutamic acid side chain:

A lysine side chain is brought into proximity

Answer 16

pKa is lowered

Question 17

The pKa of an acid depends partly on its environment. Predict the effect of the following environmental changes on the pKa of s glutamic acid side chain:

The terminal carboxyl group of a protein is brought into close proximity

Answer 17

pKa is raised

Question 18

The pKa of an acid depends partly on its environment. Predict the effect of the following environmental changes on the pKa of s glutamic acid side chain:

The glutamic acid side chain is shifted from the outside of the protein to a non-polar site inside

Answer 18

pKa is raised

Question 19

Define: Hemoglobin

Answer 19

Displays quaternary structure

Question 20

What factor(s) influence(s) the binding of oxygen to myoglobin?

Answer 20

the partial pressure of oxygen, pO2.

Question 21

Which of the following is correct concerning the differences between hemoglobin and myoglobin?

Answer 21

Hemoglobin exhibits cooperative binding of O2 while myoglobin does not.

Question 22

The structure of normal adult hemoglobin can be described as:

Answer 22

A tetramer composed of two (alpha)(beta) dimers.

Question 23

Which of the following is correct concerning fetal hemoglobin?

Answer 23

Fetal hemoglobin is composed to two (alpha) and two (theta) subunits.

Question 24

2,3-Bisphosphoglycerate:

Answer 24

1. Binds in the central cavity in the T-form of hemoglobin
2. Is present in the red blood cells.
3. Preferentially binds to deoxyhemoglobin and stabilizes it.

Question 25

What is the Bohr Effect?

Answer 25

The regulation of hemoglobin binding by hydrogen ions and carbon dioxide.

Question 26

Which of the following is correct concerning the following equilibria?
CO2 + H2O –> H2CO3

Answer 26

1. The H2CO3 dissociates to H+ and bicarbonate ion, HCO3-.
2. This reaction is catalyzed by carbonic anhydrase.
3. The majority of CO2 is transported to the lungs in the form of HCO3-.
4. An increase in the pressure of CO2 will result in a decrease of pH.

Question 27

Carbon dioxide forms carbamate groups in proteins by reaction with:

Answer 27

N-terminal amino groups.

Question 28

What would be the expected result of a Lys residue being substituted with a Ser residue in the BPG binding site of hemoglobin?

Answer 28

BPG would bind less tightly because of the loss of a postivie charge.

Question 29

The amino acid substitution of Val for Glu in Hemoglobin S results in aggregation of the protein because of _________ interactions between molecules.

Answer 29

Hydrophobic.