Protein Structure, Hemoglobin and Myoglobin MCQs

Biochemistry · 35 free questions with answers & explanations.

1. The oxygen dissociation curve of hemoglobin is sigmoidal, while that of myoglobin is hyperbolic. The sigmoidal shape of the hemoglobin curve reflects:
2. A 25-year-old African-American male with sickle cell anemia has significantly fewer painful crises since starting hydroxyurea. The biochemical mechanism by which hydroxyurea reduces sickling is:
3. A 25-year-old woman from West Africa presents with mild chronic hemolytic anemia and splenomegaly. Hemoglobin electrophoresis at alkaline pH shows a band migrating between HbA and HbS positions. Hemoglobin C (HbC, beta6 Glu→Lys) is diagnosed. Why do HbC erythrocytes form crystals (unlike HbS which forms fibers) under dehydration?
4. The Bohr effect describes decreased oxygen affinity of hemoglobin at lower pH and higher CO2. At the tissue level (low pH, high pCO2), hemoglobin releases oxygen more readily. At the molecular level, CO2 contributes to this effect by:
5. HbS (sickle cell hemoglobin) results from a beta-6 Glu→Val substitution. The polymerization of deoxyHbS is the molecular basis of sickling. Which structural feature explains why HbS polymerizes only in the deoxy conformation?
6. Hb Chesapeake has an alpha-92 Arg→Leu mutation at the alpha1-beta2 interface (the switching interface). This Hb shows increased O2 affinity (left-shifted ODC) and erythrocytosis. What is the molecular mechanism?
7. Hemoglobin M (HbM) is a variant where histidine is replaced by tyrosine at the F8 or E7 positions, stabilizing iron in the ferric (Fe3+) state. Patients present with cyanosis from birth that does not respond to methylene blue. Why does methylene blue fail to treat methemoglobinemia in HbM?
8. The Bohr effect describes the rightward shift of the oxyhemoglobin dissociation curve with increasing CO2/H+. At tissue level, CO2 enters RBCs and is hydrated to carbonic acid by carbonic anhydrase. The protons stabilize the T-state (deoxy) conformation through specific salt bridges. Which histidine residue at the alpha-beta1 subunit interface is primarily responsible for the alkaline Bohr effect?
9. Amyloidogenic proteins share a common structural feature of beta-sheet rich aggregates that bind Congo red and exhibit apple-green birefringence under polarized light. In transthyretin (TTR) amyloidosis (ATTR), the native tetrameric TTR dissociates to monomers that misfold and aggregate. Tafamidis is a small molecule that treats ATTR cardiomyopathy. What is its mechanism of action?
10. Hemoglobin M (HbM) is a rare hemoglobin variant in which certain histidine residues are substituted by tyrosine, stabilizing heme iron in the ferric (Fe3+) state. A newborn with HbM presents with cyanosis unresponsive to oxygen therapy. Methemoglobin levels are 40%. Why does 2,3-BPG fail to shift the oxygen dissociation curve rightward in this patient?
11. The Bohr effect describes the decreased oxygen affinity of hemoglobin in acidic, high-CO2 environments (tissues). The molecular mechanism involves protonation of which key residue that stabilizes the T (tense/deoxy) conformation?
12. A patient has an abnormal hemoglobin with markedly increased oxygen affinity (left-shifted ODC) and compensatory erythrocytosis. The most likely molecular basis is:
13. A 30-year-old West African man with chronic hemolytic anemia has an abnormal hemoglobin on HPLC. Hemoglobin electrophoresis shows a band migrating toward the anode more than HbS at alkaline pH. Oxygen affinity is markedly increased. Which mutation is most likely?
14. Fetal hemoglobin (HbF, alpha2gamma2) has higher oxygen affinity than adult HbA (alpha2beta2). What is the biochemical basis of the differential oxygen affinity, and how does it facilitate fetal oxygen acquisition?
15. Hemoglobin S (HbS) causes sickling because a single amino acid substitution (Glu→Val at position 6 of β-globin) allows HbS molecules to polymerise in the deoxy state. Which structural feature of the Val-6 residue is directly responsible for initiating polymer formation?
16. Fetal hemoglobin (HbF, α2γ2) has higher O2 affinity than adult HbA (α2β2) and therefore transfers O2 from maternal to fetal circulation across the placenta. The molecular basis of HbF's higher O2 affinity relates to which specific difference from HbA?
17. Hemoglobin Chesapeake is a high-affinity hemoglobin variant (increased oxygen affinity) caused by alpha-Arg92Leu substitution at the alpha1-beta2 interface. The compensatory erythropoietic response in an affected individual would be:
18. In sickle cell disease (HbSS), polymerisation of deoxy-HbS is driven by the beta-Glu6Val substitution. The critical factor that determines clinical severity during a vaso-occlusive crisis is:
19. Myoglobin has a hyperbolic oxygen dissociation curve (non-cooperative, Hill n=1) while hemoglobin shows sigmoidal cooperative binding. The structural basis for cooperativity in hemoglobin is:
20. Hemoglobin S (HbS) in deoxygenated state forms fibres due to hydrophobic interaction between the beta-6 valine of one HbS molecule and a hydrophobic pocket on an adjacent HbS molecule. The amino acid that is substituted at beta-6 in normal HbA, and the consequence of this substitution for sickling, is:
21. In a patient with congenital cyanosis from birth, pulse oximetry reads 85% SpO2 but arterial blood gas shows normal PaO2. Heinz body test is negative. Spectroscopy shows an absorption peak at 630 nm. The most likely diagnosis and the enzymatic defect causing this condition is:
22. Haemoglobin F (HbF, α2γ2) has higher oxygen affinity than HbA (α2β2). Which biochemical property of HbF explains its fetal advantage in oxygen extraction from maternal blood?
23. Haemoglobin S (HbS) polymerises on deoxygenation. The single amino acid substitution responsible is:
24. Fetal haemoglobin (HbF, α2γ2) has higher oxygen affinity than adult HbA (α2β2). The molecular basis of this difference is:
25. A 30-year-old patient with sickle cell disease is prescribed hydroxyurea to reduce vaso-occlusive crises. The primary mechanism of benefit is:
26. In hemoglobin S (HbS), glutamate at position 6 of the beta-chain is replaced by valine. During deoxygenation, HbS polymerizes. Which structural feature of the deoxy conformation DRIVES this polymerization?
27. HbS polymerises in the deoxygenated state causing sickle cell disease. At the molecular level, the specific interaction responsible for HbS polymerisation is:
28. Haemoglobin S (HbS) in sickle cell disease polymerises in the deoxy state because:
29. Methemoglobin (MetHb) contains iron in the Fe³⁺ state. Which enzyme system normally reduces MetHb back to functional Hb, and what electron donor does it use?
30. A patient with a haemoglobin variant (Hb Kansas) has threonine instead of asparagine at beta-102, at the alpha1-beta2 interface. This substitution destabilises the T-state. The clinical consequence is:
31. Haemoglobin S (HbS) polymerises when deoxygenated because valine replaces glutamate at position 6 of the beta chain. Which physical property of the Val-for-Glu substitution directly drives sickling?
32. HbS (sickle haemoglobin) polymerises in the deoxygenated state. The single amino acid substitution responsible is:
33. The Bohr effect describes rightward shift of the oxygen-haemoglobin dissociation curve at low pH/high CO2, facilitating O2 delivery to tissues. At the molecular level, this occurs because:
34. The Bohr effect describes the influence of pH and CO2 on haemoglobin oxygen affinity. At an exercising muscle where pH is low and PCO2 is high, the oxygen dissociation curve shifts RIGHT. The molecular basis is:
35. HbA1c is glycosylated haemoglobin formed by non-enzymatic glycation. The predominant site of glycation and the chemical nature of the bond initially formed is: