Chapter 6: Hemoglobin and Myoglobin
A 4-year-old patient is presented in the pediatric clinic with microcytic anemia. An analysis of his blood by non-denaturing electrophoresis reveals the following composition of hemoglobin isoforms: HbF = 75%, HbA1 = 23%, HbA2 = 2%, and HbS = 0%. Using these data, it is possible to determine that the infant is most likely homozygous for which of the following?
A. complete deletion of the α-globin locus
B. complete deletion of the β-globin locus
C. mutation in the promoter of the β-globin genes
D. nonsense mutation in the α-globin genes
E. nonsense mutation in the β-globin genes
Answer C: A mutation in the promoter region of the β-globin genes would result in reduced expression. This is evidenced by the lower than normal amount of HbA1 in this child. Under these circumstances the body will tend to compensate by continuing to express the fetal hemoglobin genes at higher than normal levels resulting in potentially dramatic increases in measured HbF. Normal levels of HbF in a 4-year-old child would be around 0% to 2%, whereas, this child shows significant increase in HbF of 75%.
When the malarial parasite invades a red blood cell, its metabolic waste products result in the acidification of the cytoplasm. Which of the following best describes the consequences of this acidification on the activity of hemoglobin (Hb)?
A. formation of carbaminohemoglobin is enhanced
B. hemoglobin tetramers become less stable and the complex dissociates
C. there is a shift to a more R state conformation
D. there is a shift to a more T state conformation
E. there is no effect from the acidification
Answer D: The principal negative regulator of the affinity of hemoglobin for oxygen is proton, H+. The acidification of the erythrocyte cytoplasm by malarial parasite metabolism would be reflected by a significant increase in [H+] which would, in turn, result in a higher level of T state hemoglobin.
In one form of β-thalassemia, patients have significantly reduced levels of β-globin transcripts. Notably these β-globin transcripts are less than half the length of the normal β-globin mRNA. These patients exhibit elevated levels of HbF and no detectable HbA1. Which of the following best explains the molecular reason for these observations?