Question

1. Describe using thermodynamics the enthalpic stabilizatiok of the T-state and whether high or low [O2] would be favored and why.

2. Predict the effect of red blood cells expressing (producing) myoglobin instead of hemoglobin.

3. List the interactions that stabilize the R-state (oxyhemoglobin), pick all that are correct.

A) Numerous salt bridge interactions in the central cavity

B) Coordinate covalent bonds (4) between O2 and heme

C) H-bonding (4) between O2 and distal His

4. Where are the interactions identified in #3 occuring? Pick all that are correct.

A) Between subunits

B) In central cavity

C) Oxygen binding site (pocket)

5. The affinitt of hemoglobin for oxygen is increased by: (Pick all that are correct.)

A) Addition of H+

B) Binding of CO2

C) Binding of Oxygen

D) Binding of BPG

6. Briefly explain why HbA does not form intermolecular polymers like HbS does.

Answer 1

1. Allosteric effects in hemoglobin arise from the equilibrium between two energetic states of the molecule: a tense state, T, and a relaxed state, R. The two states differ from each other in their affinity for ligand and in the interactions between subunits. In the T state, constraints between subunits oppose the structural changes resulting from ligand binding, thus lower ligand-binding affinity. There are four sites present in hemoglobin that are structurally stabilized in the R relative to the T state. Binding of oxygen to the deoxygenated (deoxy)-T state occurs with low affinity. However, the binding of the ligand destabilizes the T state and makes it more likely to switch to the high-affinity oxygenated (oxy)-R state. Normally it is the intense straining of the T-state that drives deoxyhemoglobin to bind to oxygen; once oxygen is bound, the T-state loses its strain and relaxes into the R-state.

A number of salt bridges occur in the Tense state which are broken in the Relaxed state

3. . List the interactions that stabilize the R-state (oxyhemoglobin), pick all that are correct.

B) Coordinate covalent bonds (4) between O2 and heme

C) H-bonding (4) between O2 and distal His

4. Where are the interactions identified in #3 occuring? Pick all that are correct.

C) Oxygen binding site (pocket)

5. The affinitt of hemoglobin for oxygen is increased by: (Pick all that are correct.)

C) Binding of Oxygen

Bisphosphoglycerate, or BPG, is one of many allosteric regulators for hemoglobin. This molecule binds to the central cavity of the deoxyhemoglobin version of hemoglobin (T-state) and stabilizes it. The increased stability of the T-state results in a decreased affinity for oxygen

6.

Sickle hemoglobin (HbS) is a point mutation of the two β subunits in normal Hb (HbA) that leads to nucleated polymerization and accompanying pathology. The replacement of β6 Glu→Val creates a hydrophobic surface protrusion that can dock with a corresponding hydrophobic pocket in a partner molecule and generate long, stiff polymers that underlie the pathology of the disease. HbA has the same axial contacts as HbS; however, because of the high energetic cost of burying a charged glutamic acid in the hydrophobic lateral receptor region, it does not form polymers .