Pulmonary Biochem - Hemoglobin Variants Flashcards
What chromosome leads to the alpha-like group of hemoglobin?
Chromosome 16
What chromosome leads to the beta-like group of hemoglobin?
Chromosome 11
What are the three types of embryonic hemoglobin in the order they appear?
Gower1 - zeta2, epsilon2
Portland - zeta2, gamma2
Gower2 - alpha2, epsilon2
What is fetal hemoglobin? When does it appear? Persist?
Fetal - alpha2, gamma2
Begins week 10, predominates through week 38
Can last into adulthood
What are the two main types of adult hemoglobin?
A - alpha2, beta2
A2 - alpha2, delta2
Where is the focus control region in relation to the gene?
Far upstream
What is alpha-globin modulated by? What does this do?
ATRX, influences chromatin remodeling and DNA methylation (modulates LCR for alpha-globin cluster)
What can mutations in ATRX lead to? Clinically?
Alpha-thalassemia - ability to make cells but not put chromatin in. Also modulates heme production
Metal retardation and myelodysplasia (not making cells)
What is AHSP? What does it do?
Alpha-hemoglobin-stabilizing protein
Enhances folding and solubility of alpha-globin
How does AHSP level relate/explain clinical variability in pts with identical thalassemia mutations?
The more AHSP, the more stable the alpha, and the less precipitates.
Precipitates are bad, lead to more severe disease
What are 4 places for mutations that can alter oxygen affinity and solubility?
Mutations in: hydrophillic surface Hydrophobic center AA forming contact points Key histidine in F helix
What two properties are affected by hemopathies?
Solubility of oxygen
Reversible oxygen binding
What AA switch leads to HbS (sickle cell hemoglobin)?
Beta 6 glu -> valine
What are Heinz bodies? When are they seen?
Aggregated hemoglobin precipitates
Seen when stained for reticulocytes (just come out of bonemarrow)
What is hemoglobin Constant Spring?
Point mutation (“sense”) - stop codon turned to normal codon, making mRNA unstable, decreasing amount and lifespan of cells
