Hemoglobinopathy Biochemistry

  1. Hemoglobin ____ state tetramer is tight for Oxygen to bind, while ____ state is more relaxed, and oxygen binds to destabilize the alpha1-beta2 interface
    • T
    • R
  2. Alpha1-beta1 interface describe what structure of hemoglobin? Vs alpha1-beta2
    • Alpha1-beta 1 is heterodimer
    • Alpha1-beta 2 is when two heterodimers come together to form the tetramer
  3. T/F: binding of oxygen destabilizes the tetramer and so on that graph thing (pO2/% saturation) the line would be higher and shift to the left of wild type
    True; this describes hemoglobin when in R state
  4. What does the T state hemoglobin curve look like?
    Lower and shift to the right. This is the ‘stabilized’ tetramer where affinity to oxygen is low
  5. Patient presents with “ruddy” appearance skin, this is probably due to a mutation that ______ the alpha1beta2 interface. Whereas another patient comes in looking blue, this condition is more likely to be due to mutation that causes the interface to be more _____.
    • Ruddy appearance-> destabilized tetramer (R state, O2 has high affinity to tetramer, so while there’s enough O2 binding to hemoglobin, the high affinity is not letting the O2 be delivered to tissues, causing the body to send more blood to the periphery resulting in the appearance)
    • Blue appearance -> stabilized tetramer (locked in T state, not enough O2 delivered)
  6. Thalassemia is defined as what to the globin chains?
    Decreased synthesis of globin chains (vs. sickle cell is defective globin chain due to mutations, but synthesis of globin is intact)
  7. Sickle cell disease has a mutation of Beta globin with GLU6-____ mutation. HbC disease is GLU6-___ mutation, and HbE disease is a GLU29-____.
    • VAL
    • LYS
    • LYS
  8. T/F: sickle cell anemia, thalassemia, HbC and HbE are all classified as microcytic anemia
    False; sickle cell anemia is hemolytic anemia, which is normocytic; thalassemia, HbC and HbE are microcytic anemia
  9. What is the globin composition for HbA1 tetramer, vs HbA2 tetramer, vs Fetal hemoglobin (HbF)?
    • HbA1 it is dimers of alpha and beta
    • HbA2 is dimers of alpha and delta
    • HbF is dimers of alpha and gamma
  10. What do these mean: HbCC, HbEE, HbSS, HbSA, HbSC, HbSE etc?
    These are the beta globinopathy. HbCC and HbEE have mutations at the gene for beta globin (subclinical); HbSS being sever sickle cell disease and other variation of with S in it varies in severity: HbSA is subclinical because it has one good Beta globin, while HbSC and HbSE do not have wildtype beta globins so those are moderate in severity.
Card Set
Hemoglobinopathy Biochemistry
HemeOnc Midterm