Question

In class, we discussed how H₁₄₆ of the β -chain of normal adult hemoglobin ends up in close proximity to D₉₄ on the same chain when oxygen is delivered to the tissues. In hemoglobin Hiroshima, however, H₁₄₆ on the β -chain has been changed to a D through mutation. What effect, if any, does this mutation have on the Bohr Effect of this mutant hemoglobin?

Choose all correct answers.

Group of answer choices

diminishes the H+ portion of the Bohr Effect

increases the H+ portion of the Bohr Effect

has no effect on the CO2 portion of the Bohr Effect

increases the CO2 portion of the Bohr Effect

has no effect on the H+ portion of the Bohr Effect

diminishes the CO2 portion of the Bohr Effect

Answer 1

Answer- In hemoglobin Hiroshima, however, H146 on the β -chain has been changed to a D through mutation.

Bohr Effect of this mutant hemoglobin are

1. diminishes the H+ portion of the Bohr Effect

2. diminishes the CO2 portion of the Bohr Effect

Explanation

Histidine present at 146 position of beta chain of haemoglobin contributes to the alkaline Bohr effect. This interaction is disrupted in Hb Hiroshima (β146 His > Asp). These variants show decrease Bohr effect with reduced release of O2 in acidic environment.

Bohr effect is the regulation of oxygen binding to the haemoglobin by concentration of CO2 and Hydrogen ions.

Affinity of haemoglobin to oxygen increase with increase in pH and decreases with decrease in pH.

At low pH, when H+ concentration and CO2 concentration is high, haemoglobin loses or releases bound oxygen into the tissues and binds to CO2.

While at High pH, when both when H+ concentration and CO2 concentration is low, haemoglobin affinity for oxygen increases.

Both H+ and CO2 are the heterotrophic regulators of haemoglobin.

Chemical basis of Bohr’s effect

H+ effect- requires amino terminal and presence of histidine at 146 position of β-chain and at 122 position of α- chain.

When haemoglobin is not bound to oxygen (low pH)- In deoxyhemoglobin state, the β-H146 interacts with lysine residue of α subunit through its terminal carboxylate group forming salt bridges. Due to this interaction side chain of histidine β146 forms salt bridge with acidic amino acid aspartate present at 94 position of beta chain when the imidazole group of the histidine is protonated. This interaction stabilizes the quaternary structure of deoxyhemoglobin, resulting into facilitating release of any bound oxygen into tissues.

CO2 reacts with amino terminal forming negatively charged carbamate. These carbamates interact with αβ dimers through salt bridges and stabilizes the T-state form of haemoglobin, further stabilizing the deoxyhaemoglobin state and facilitating release of oxygen.

At high pH, imidazole group of histidine β146 is not protonated and hence no salt bridge is formed.