.2. Which one of the following statements concerning the ability of acidosis to precipitate a crisis in sickle cell anemia is correct?
A. Acidosis decreases the solubility of HbS.
B. Acidosis increases the oxygen affinity of hemoglobin.
C. Acidosis favors the conversion of hemoglobin from the taut to the relaxed conformation.
D. Acidosis shifts the oxygen-dissociation curve to the left.
E. Acidosis decreases the ability of 2,3-bisphosphoglycerate to bind to hemoglobin.
Correct answer = A. HbS is significantly less soluble in the deoxygenated form, compared with oxyhemoglobin S. Decreased pH (acidosis) causes the oxygen-dissociation curve to shift to the right, indicating decreased oxygen affinity (increased delivery). This favors the formation of the deoxy, or taut, form of hemoglobin and can precipitate a sickle cell crisis. The binding of 2,3bisphosphoglycerate is increased, because it binds only to the deoxy form of hemoglobin.
.3. Which one of the following statements concerning the binding of oxygen by hemoglobin is correct?
A. The Bohr effect results in a lower oxygen affinity at higher pH values.
B. Carbon dioxide increases the oxygen affinity of hemoglobin by binding to the C-terminal groups of the polypeptide chains.
C. The oxygen affinity of hemoglobin increases as the percentage saturation increases.
D. The hemoglobin tetramer binds four molecules of 2,3bisphosphoglycerate.
E. Oxyhemoglobin and deoxyhemoglobin have the same affinity for protons.
Correct answer = C. The binding of oxygen at one heme group increases the oxygen affinity of the remaining heme groups in the same molecule. A rise in pH results in increased oxygen affinity. Carbon dioxide decreases oxygen affinity because it lowers the pH. Moreover, binding of carbon dioxide to the N-termini stabilizes the taut, deoxy form. Hemoglobin binds one molecule of 2,3-bisphosphoglycerate. Deoxyhemoglobin has a greater affinity for protons than does oxyhemoglobin.
.4. β-Lysine 82 in HbA is important for the binding of 2,3-bisphosphoglycerate. In Hb Helsinki, this amino acid has been replaced by methionine. Which of the following should be true concerning Hb Helsinki?
A. It should be stabilized in the taut, rather than the relaxed, form.
B. It should have increased oxygen affinity and, consequently, decreased oxygen delivery to tissues.
C. Its oxygen-dissociation curve should be shifted to the right relative to HbA.
D. It results in anemia.
Correct answer = B. Substitution of lysine by methionine decreases the ability of negatively charged phosphate groups in 2,3-bisphosphoglycerate (2,3-BPG) to bind the β subunits of hemoglobin. Because 2,3-BPG decreases the oxygen affinity of hemoglobin, a reduction in 2,3-BPG should result in increased oxygen affinity and decreased oxygen (O2) delivery to tissues. The relaxed form is the high-oxygen-affinity form of hemoglobin. Increased oxygen affinity (decreased delivery) results in a left shift in the oxygen-dissociation curve. Decreased delivery of O2 is compensated for by increased RBC production.
.5. A 67-year-old man presented to the emergency department with a 1-week history of angina and shortness of breath. He complained that his face and extremities had taken on a blue color. His medical history included chronic stable angina treated with isosorbide dinitrate and nitroglycerin. Blood obtained for analysis was brown. Which one of the following is the most likely diagnosis?
A. Carboxyhemoglobinemia