Question

1. What other factors will promote oxygen release from hemoglobin? What factors promote binding of oxygen to hemoglobin?
2. High levels of CO2 will promote oxygen release/binding (Pick one). Explain in terms of metabolic pathways why high levels of CO2 would promote release/binding of oxygen
3. How does the protein sequence of hemoglobin differ from normal hemoglobin? How does this change affect the structure of the protein? Explain what happens on the protein level to cause the sickling of the Red blood cells.

Answer 1

1.The factors that effect the release of O2 from heamoglobin are H+ ion concentration, body temperature, PCO2 levels i, 2,3-diphosphoglycerate levels in blood. Increase in H+ ion concentration , increase in CO2, increase temperature, increase 2,3-diphosphoglycerate levels accelerates release of O2 from hemoglobin by decreasing the affinity of O2 to hemoglobin.

The factors that promote binding of hemoglobin are decreased H+ ion concentration, decreased CO2 levels, decreased 2,3-diphosphoglycerate concentration and decrease in temperature will promote binding of hemoglobin to O2.

2.High levels of CO2 will release O2 from hemoglobin.

Burning of glucose by aerobic path liberates lot of CO2 which needs to be eliminated from the body. CO2 diffuses in to blood. When CO2 enters in to blood and increases its concentration in blood plasma, it immediately forms carbonic acid (H2CO3).

Since carbonic acid is an unstable compound, it breaks in to HCO3- and H+ ions. Increase in H+ ion concentration will make the blood slightly acidic. Under such acidic conditions, the hemoglobin molecule looses the affinity to bind to O2. This results in O2 release.\

3. In sickle cell anemia due to a mutation in the gene coding beta chain of hemoglobin, protein formed will be slightly different. Mutation changes one nucleotide leading to change in the amino acid from glutamic acid to valine. Sixth amino acid changes in to valine from glutamin. This is how sickle hemoglobin differs from normal in protein composition.

Valine is hydrophobic and glutamine is hydrophilic. This change from hydrophilic amino acid to hydrophobic amino acid will change the 3-dimensional structure of the hemoglobin molecule. As valine is present on the surface of the hemoglobin molecule, hemoglobin solubility in water reduces. Hydrophobic valine develops bonds with other hydrophobic amino acids present in the beta chains making long fibers and distorting the structure of the protein.

Under low O2 concentrations this results in crystallization of hemoglobin which causes distortion of the structure of the RBC. So the RBCs become sickle shaped under low O2 partial pressures.