Hemoglobin Flashcards
Why does hemoglobin have a lower affinity for oxygen than myoglobin?
hemoglobin needs to be able to dissociate with oxygen when it gets to the tissues that need it such as muscle. myoglobin strips the oxygen from hemoglobin
Why does hemoglobin exhibit cooperativity (binds more O2 when it has some O2 already bound to it?)
Because it needs to saturate with oxygen quickly in the lungs
How does hemoglobin increase in affinity for oxygen as each tetramer binds with an oxygen?
the binding of oxygen changes the conformational shape of the tetramer so that each subunit becomes more mechanically favorable for binding, moves from tense to relaxed state.
What is 2,3-Bisphosphoglyceric acid?
It interacts with deoxygenated hemoglobin beta subunits by decreasing their affinity for oxygen, so it allosterically promotes the release of the remaining oxygen molecules bound to the hemoglobin, thus enhancing the ability of RBCs to release oxygen near tissues that need it most.
What conditions decrease HGB’s affinity for oxygen?
Acidic environments, high temp, elevated CO2, and increase in 2,3-Bisphosphoglyceric acid
How does sickle cell disease harm the body?
in low oxygen state, hemoglobin becomes susceptible to polymerization -> filaments -> causes red blood cells to become misshapen, and can cause clogging of capillaries and hemolysis by puncturing endothelium
Structural hemoglobinopathies.
These disorders are generally caused by missense mutations that alter the primary structure of Hgb chains. Sickle (HbS) disease is an example.
Thalassemias.
These disroders are caused by imbalances in the amounts of α- and β-chain synthesis, degradation, or Hb tetramer assembly, leading to excess production of unassembled globin chains.
Hereditary persistence of fetal hemoglobin (HSPS).
These are regulatory disorders in which the switch from HbF to HbA fails to occur in early childhood. HSPS by itself does not lead to major pathology but it can be a strong genetic modifier of other hemoglobinopathies and thalassemias.
Why are recessive disorders of Hb β-chains far more frequent, and tend to be more severe, than disorders of the Hb α-chains?
Because there are two identical copies of the Hb α-chain gene on chromosome 16, leading to 4 copies of α-chain gene.
Why are disorders of Hb β-chains later to present phenotypically than disorders of the Hb α-chains?
a-chains are present prenatally, whereas B-chains are not present until childhood, when body switches from y-chains to B-chains.
what is the genotype and phenotype of a-thalasemia trait?
–/aa or -a/-a genotype, phenotype is expression of 50% normal a-globin production
what is the genotype and phenotype of simple a-thalasemia disease?
–/-a
25% normal a-globin production
What are the molecular mechanisms of a-globin gene deletion and a-globin gene triplication?
unequal crossing over
