Question

Sigmoid vs hyperpolic curves

What is an allosteric effector? What are they for Hb?

With respect to binding, what is the difference between fetal Hb and maternal Hb? How does a pH change affect oxygen binding to Hb?

What is the effect of BPG? What are allosteric effectors in other species??

How does CO affect Hb and Mb?

How does carbon dioxide bind to Hb? Draw a carbamate structure for Hb – N-terminal aa is modified

Answer 1

Ans. #1. Allosteric effector: A molecule that binds at the allosteric site of the protein and affects its affinity of the true ligand at the active/binding site.

For example, BPG is an allosteric effector of HB because it binds the protein at the allosteric site and reduce the affinity of binding site for O₂ (true ligand).

#2. 2,3-BPG is an allosteric modulator. It binds to N-terminal valine residue of β-subunit of HbA (α₂β₂). This binding causes transition of R-state (HbO₂) into T-state (deoxyHb) by stabilizing the T-state. Stabilization of T-sate by 2,3-BPG decreases the affinity of Hb for O₂, which in turn triggers the dissociation of O₂ from HbO₂.

Fetal hemoglobin (a2y2) is inert to BPG (2,3-bisphosphoglycerate) whereas the maternal Hb (a2b2) exhibits lower binding affinity for O₂ after BPG binds to it.

#3. Higher concentration of hydrogen ions [H⁺] in blood favors T-state of hemoglobin. So, higher [H⁺] or, in turn, lower pH (more acidic) causes of transition from R-state to T-state leading to dissociation of O₂ from oxyhemoglobin (HbO₂).

Alternately, lowering the pH from 7.4 to 7.2 increases apparent [H⁺] in blood. The more is [H⁺], the more is protonation of Hb (binding of H⁺ to Hb). Greater extent of Hb protonation favors the transition from R-state (HbO₂) to T-state (deoxyHb).

Therefore, lowering of pH lowers the affinity of Hb for O₂.

#4. 2,3-BPG is an allosteric modulator. It binds to N-terminal valine residue of β-subunit of HbA (α₂β₂). This binding causes transition of R-state (HbO₂) into T-state (deoxyHb) by stabilizing the T-state. Stabilization of T-sate by 2,3-BPG decreases the affinity of Hb for O₂, which in turn triggers the dissociation of O₂ from HbO₂.

#5. Carbon monoxide: Carbon monoxide (CO) is a colorless, odorless poisonous gas. It competes with O₂ for the O₂-binding site in hemoglobin as well as myoglobin. It’s affinity for O₂-binding site in Hb is around 210 times greater than that of O₂ molecules. It’s affinity for O₂-binding site in Myb is around 60 times greater than that of O₂ molecules. The resultant HbCO complex, called carboxyhemoglobin, is highly stable and can remain as such for long times. Moreover, binding of CO to HbO₂ also inhibits O₂ transport to and from RBCs. CO bound Hb or Myb in venous blood does not get oxygenated (fails to load O₂) in lungs during re-oxygenation. Also, CO bound HbO₂ and MybO­₂ in arterial blood and muscles, respectively, does not release O₂ to the tissues.

#6. CO₂ is covalently linked to –NH₂ of amino acids of Hb, the resultant structure being called carbamino. Since Hb is the most abundant protein in blood, the major fraction of carbamino compounds is in form of carbaminohemoglobin (CO₂ covalently linked to α-NH2 group of N-terminal residues of α- and β- chains).

Note: “Carbamino” is the preferred term for association of CO₂ with the –NH₂ group of amino acids.

Carbamate is a different group of compounds