Deck 6: Hemoglobin and Myoglobin

Question 1

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%, HbA
1 = 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 a-globin locus
B) complete deletion of the b-globin locus
C) mutation in the promoter of the b-globin genes
D) nonsense mutation in the a-globin genes
E) nonsense mutation in the b-globin genes

Answer 1

mutation in the promoter of the b-globin genes

Question 2

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 2

there is a shift to a more T state conformation

Question 3

In one form of b-thalassemia, patients have significantly reduced levels of b-globin transcripts. Notably these b-globin transcripts are less than half the length of the normal b-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?

A) addition of 7-methylguanosine to the b-globin mRNA
B) covalent modification of the b-globin protein
C) improper folding of the b-globin protein
D) promoter mutations in the b-globin gene
E) splicing alteration of the b-globin mRNA

Answer 3

E
EXPLANATION: Numerous b-thalassemias result from mutations in the sequences that control proper splicing of the b-globin transcript. These mutations lead to b-globin mRNAs that are shorter or longer than the normal b-globin mRNA. Although mutations in the promoter region of the b-globin gene will lead to reduced levels of expression and thus, to reduced levels of b-globin mRNA, they generally do not result in mRNAs that are shorter than normal.

Question 4

Although HbF represents fetal hemoglobin, some level of this form of hemoglobin persists in the adult. Which of the following represents the value for HbF in adults above which it would likely reflect some underlying pathophysiology?

A) 0.1%
B) 0.5%
C) 2.0%
D) 5.0%
E) 15%

Question 5

You are treating a patient who presents with microcytic anemia. Additional microscopic findings demonstrate the presence of inclusion bodies in the red blood cells. Electrophoresis of erythrocyte protein extracts shows a large excess of b-globins and a near complete lack of a-globins. Which of the following disorders most closely correlates to your findings?

A) hemoglobin H disease
B) hereditary persistence of fetal hemoglobin
C) hydrops fetalis
D) sickle cell anemia
E) b-thalassemia major

Question 6

You are studying the oxygen-binding characteristics of a synthetic oxygen transport compound. You want to design the compound so that it most closely mimics the oxygen affinity of native hemoglobin protein. If you are successful, addition of which of the following to a test solution would have the greatest negative effect on the ability of your compound to bind oxygen?

A) 2,3-BPG
B) bicarbonate ion
C) carbonic acid
D) phosphoric acid
E) water

Question 7

Which of the following is referred to as a qualitative hemoglobinopathy?

A) hemoglobin H disease
B) hydrops fetalis
C) sickle cell anemia
D) a-thalassemia
E) b-thalassemia

Question 8

Aside from the obvious presence of HbS hemoglobin in individuals with sickle cell disease, which
Of the following hemoglobins is also found at high frequency in these individuals?

A) HbA _1c
B) HbA ₂
C) HbC
D) HbF
E) HbH

Question 9

Which of the following is the primary source of the H⁺ that leads to displacement of O₂ from hemoglobin in the tissues?

A) 2,3-BPG
B) bicarbonate ion
C) carbonic acid
D) phosphoric acid
E) water

Question 10

The "Bohr effect" is best described by which of the following statements?

A) binding of O₂
B) covalent attachment of CO₂ forming hemoglobin carbamate
C) release of O₂ from hemoglobin in response to the buffering of Cl− by hemoglobin
D) release of CO₂ from erythrocytes when they enter the high O2 concentration of the alveoli
E) release of O₂ from hemoglobin in response to the buffering of H+ by hemoglobin

Question 11

Beta-thalassemias are genetic disorders in the synthesis of the b-globin chains in hemoglobin. Affected individuals usually begin to exhibit some degree of anemia at about 6 months of age. Therapy for severe anemia involves multiple transfusions. What is the most serious complication of transfusion therapy?

A) cardiac arrhythmias
B) copper overload
C) globin overload
D) increased blood viscosity
E) iron overload

Question 12

The thermodynamics of oxygen binding to hemoglobin are highly ordered. Which of the following
Reflects the physical characteristics relating the binding of O₂ to hemoglobin?

A) causes a large shift of the surrounding secondary structures leading to decreased affinity of the deoxy subunits for CO₂
B) is cooperative, meaning that after the first O2 binds, the other subunits are more readily oxygenated
C) occurs with equal affinity at all 4 subunits
D) results in a release of the heme from the interior to the exterior of the a-subunits, leading to an increase in O₂ affinity of the b-subunits
E) results in a release of the heme from the interior to the exterior of the b-subunits leading to an increase in O₂ affinity of the a-subunits

Question 13

Carbon monoxide (CO) poisoning is a significant cause of mortality in the United States. Which of the following statements about CO is correct?

A) competes with CO₂ for a common binding site on hemoglobin
B) competes with O₂ for a common binding site on hemoglobin
C) has a lower affinity for hemoglobin than does O₂
D) irreversibly binds to hemoglobin
E) is normally a perfusion-limited gas

Question 14

A 35-year-old apparently healthy man undergoes a medical examination while applying for life insurance. He is not anemic. His hemoglobin electrophoresis is reported as: HbA₁, 62%; HbS, 35%; HbF, 1%; HbA₂, 1%; no variant C, D, G, or H bands are detected. The most likely diagnosis is which of the following?

A) sickle cell disease
B) sickle thalassemia minor
C) sickle trait
D) thalassemia major
E) thalassemia minor

Question 15

You are a third-year emergency room (ER) resident tending to a 48-year-old woman who has come to the ER complaining of increasing fatigue and mild shortness of breath. Blood work reveals a hypochromic anemia with a hemoglobin of 10.4 g/dL, MCV of 76 m/m³, MCHC of 29 g/dL, and a decrease in the absolute reticulocyte count. WBC and platelet counts are within normal limits. Serum iron and ferritin levels are low and total iron-binding capacity is elevated. Which of the following conditions best accounts for these findings?

A) anemia of chronic disease
B) aplastic anemia
C) hypothyroidism
D) iron deficiency
E) pernicious anemia

Question 16

A 27-year-old female who is 5 months pregnant has come to her ob-gyn due to a fear that something wrong with her baby. Following her previous routine visit she noted that her baby was moving frequently but in the past 2 days she has not felt any movements. Her physician performs a routine physical exam and notes that the fetal heart rate is tachycardic. The physician orders an ultrasound and during this exam notes a significant pleural and pericardial effusion. A diagnosis of potential hydrops fetalis is made with additional diagnostic tests ordered. Which of the following is most closely associated with non-immune (Rh)-mediated hydrops fetalis?

A) Cooley's anemia
B) hemoglobin Barts
C) hemoglobin H disease
D) thalassemia major
E) thalassemia minor

Question 17

Hemoglobin and myoglobin are proteins composed primarily of which of the following types of secondary structures?

A) amide bond
B) disulfide bond
C) a-helix
D) b-pleated sheet
E) triple helix

Question 18

Sickle cell disease is associated with a mutated form of hemoglobin (HbS) that aggregates to produce long rods within erythrocytes. Which of the following best explains how the mutation leads to aggregation of HbS?

A) creation of a hydrophobic area on the surface of the b-chain
B) creation of an abnormal ratio of a-chains to b-chains
C) prevention of assembly of b-chains with a-chains
D) prevention of b-chain from binding heme
E) production of a truncated b-chain

Question 19

Which of the following types of bonds is primarily responsible for the aberrant aggregation of deoxy HbS molecules resulting from the glutamate to valine mutation in the sixth position of the b-globin chain?

A) amide
B) covalent
C) disulfide
D) hydrophobic
E) ionic

Question 20

During an experiment on hemoglobin function, knockout mice that are unable to synthesize globin proteins are created. Absence of which of the following globin proteins is most likely to be incompatible with life in these mice?

A) a
B) b
C) δ
D) g