Hemoglobin Flashcards
Hemoglobin Structure
2 Alpha Subunits, 2 Beta Subunits
Gene Families of Alpha and Beta
Alpha: Two genes on chromosome 16
Beta: One gene on chrmosome 11
Transient Expression of Hemoglobin
Alpha: Zeta(Embryonic), Alpha(Fetal and Adult)
Beta: Epsilon (Embryonic), Gamma (Fetal), Beta (Adult), Delta (Minor Adult Contribution)
Embryonic goes away by 6 weeks after conception
Fetal = Adult at 6 weeks after birth
Percent of O2 carried by RBCs
98%+, due to low solubility in plasma all of which is bound to Hb
Carriage of CO2 by RBCs
Conversion to bicarbonate by carbonic anhydrase and is primarily soluble in RBC cytosol and plasma. Only 14% bound to Hb
Tertiary structure of Hemoglobin
Both alpha and beta are very similar, evolutionarily related to myoglobin
Fe2+ prototporphyin IX prosthetic group for O2 binding
Fe3+ cannot bind to O2 and is called methemoglobin
Hemoglobin vs Myoglobin Binding Curve
Hemoglobin is sigmoidal due to cooperativity from its subunit structure, myoglobin is normal hyperbolic. As a result, myoglobin binds much better at low O2 (lower P50)
Fetal vs Adult Hb
Fetal Hb has lower P50 so it has stronger binding affinity than adult Hb
Sequential Cooperativity and States
Hb has two states R and T, where R is prefered when oxygenated and T when deoxygenated. Each additional oxygen increases the likelihood of transitioning to R and decreases likelihood of transitioning to T.
Conformational change during oxygen binding
Without O2 the Fe ion is pulled away from the plane of porphyrin by a His residue. O2 pulls the Fe back into the plane of the ring and moves the His residue away. This helps promote the R state by shifting the subunits.
Hydrogen effect on Hb
Decreases affinity
CO2 effect on Hb
Reduces O2 affinity
DPG effect on Hb
Reduces Hb affinity
Stabilizes T-state differentiating Hb from Myo
Increases during periods of extended (hours and days) hypoxia, such as high altitudes
Temperature effect on Hb
Increase in temperature reduces Hb affinity for O2
