Question

1. Explain how the oxygen affinity of hemoglobin can affect the followings:

1.1 Amino acid substitutions that disrupt H-bonding at the α,β-interface

1.2 Substitution L136P, which destabilizes the subunit interactions

1.3 Disease in which the individual has increased levels of fetal hemoglobin

1.4  Consumption of methanol that causes a drop in blood pH (Metabolic acidosis)

Answer 1

1.1 ) when the Substitutions of these amino acids Asn, Glu, and Leu for Gln at the β131 position of the hemoglobin molecule result in recombinant hemoglobins with moderately lowered oxygen affinity and high cooperativity compared to human normal adult hemoglobin . The mutation site affects the hydrogen bonds present at the α1β1-subunit interface between α103His and β131Gln as well as that between α122His and β35Tyr.

1.2) when it is undergoing destabilizing the substituent interactions results in the high-affinity R state and stabilizing the low-affinity T state, which leads to an overall decrease in oxygen affinity.

1.3 ) fetal hemoglobin differs most from adult hemoglobin in that it is able to bind oxygen with greater affinity than the adult form, giving the developing fetus better access to oxygen from the mother's bloodstream.fetal hemoglobin production can be reactivated pharmacologically, which is useful in the treatment of diseases such as sickle-cell disease.

1.4 ) when  Consumption of methanol that causes a drop in blood pH with increased acidity, the hemoglobin binds less O₂. This is known as the Bohr effect. A reduction in the total binding capacity of hemoglobin to oxygen due to reduced pH is called the root effect. This is seen in bony fish. The binding affinity of hemoglobin to O₂ is greatest under a relatively high pH.