Question

1.Which of the following statements is NOT an explanation for how oxygen is released from oxy-hemoglobin.

A. Carbon dioxide has a stronger affinity than oxygen to heme and displaces oxygen in tissues.

B. The formation of carbonic acid lowers the oxygen affinity of hemoglobin in tissues.

C. The structure of deoxyhemoglobin is stabilized by the interaction with BPG.

D. Salt bridges are formed with N-terminal carbamates in deoxyhemoglobin.

E. Salt bridges are formed between acidic and basic side chains of His146 and Asp94, respectively in deoxyhemoglobin

2. Which of the following description of hemoglobin S (HbS) forming fibrous aggregates is FALSE?

A. Valine at position 6 of the β chains forms hydrophobic interaction with other HbS.

B. Formation of aggregates occurs more severely in homozygotes, i.e. both alleles carrying the mutation.

C. The aggregates distort the shape of the red blood cells.

D. The formation of aggregates occurs only in the deoxygenated form of HbS.

E. More aggregates are formed in the lungs.

3. Predict the possible outcome if HbS is stripped of BPG?

A. More tendency of HbS to form aggregates.

B. Less tendency of HbS to form aggregates.

C. No effect on HbS aggregation.

D. HbS form aggregates more rapidly.

E. The sickled cells clog blood capillaries more severely.

4. What would be the change of oxygen dissociation curve of the patient with sickle cell anemia, compared to that of a normal person?

A. Left shift

B. Right shift

C. Up shift

D. No change

E. Becomes hyperbolic

Answer 1

1) CO2 binds with amino group of globin protein which is a part of Hb, It does not binds with haem part of Hb. It has stronger affinity than oxygen to globin part of Hb and displaces oxygen in tissues as the partial pressure of CO2 is higher as compared to O2. The formation of carbonic acid takes place takes place in the tissue which dissociates into H+ and bicarbonate ions resulting in increase of H+ concentration and decrease in pH which lowers oxygen affinity of haemoglobin in tissues, resulting in dissociation of O2 from Hb. The structure of deoxyhaemoglobin is stabilized by BPG by binding to it strongly as it forms salt bridges with cationic lysine and histidine residues and N-terminal amino groups of subunits. Deoxyhaemoglobin is stabilized by a network of salt bridge formed with N-terminal carbamates anddecreases oxygen affinity of proton. Salt bridges are formed between acidic and basic side chains of histidine and aspartic acid respectively in deoxyhaemoglobin.

2) HbS forms the allelic pair in sickle cell anaemia. It is a mutation (transversion) of the gene controlling -chain of Hb. The mutated gene is called HbS. It causes one change in amino acid sequence of -chain. It replaces glutamic acid (Glu) present at 6th position by amino acid valine (Val). The mutant Hb undergoes polymerisation under low O2 tension causing distortion in its shape from biconcave disc to sickle-like structure. Homozygotes (carrying both the mutated gene, HbS) are more prone to diseased and die before attaining maturity. Valine residue at 6th position of the -chain of deoxy HbS lies on the surface on the surface of the protein. This hydrophobic residue, forms a hydrophobic interaction with adjacent HBS. When HbS is deoxygenated it undergoes polymerisation and formation of aggregates occurs with distortion in its shape. The formation of aggregates is triggered where there is low oxygen tension like in spleen and bone marrow where more aggregates are formed.

3) The extent of sickling increases by variables which increase the proportion of HbS in deoxy state i.e reduces the affinity of HbS for oxygen. So high levels of BPG increases the amount of HbS. If HbS is stripped off from BPG, then affinity of HbS for O2 increases and BPG does not able to bind now, so there is less tendency of forming aggregates by HbS.

4) The oxygen dissociation curve for sickle cell anaemia patient, shift markedly towards right as compared to that of a normal person, increasing the partial pressure of O2.