Hemoglobin Flashcards
Myoglobin basic structure
The protein chain hemoglobin is composed of - the tetramer subunit. α-helix, with tightly bound heme prosthetic group. Intracellular storage.
Myoglobin structure
Heme groups coordinate heme coordinates to iron.
Proximal histidine, heme, iron, O2, distal histidine.
Dissociation constant
Kd = [Mb][O2]/[MbO2]
Fractional saturation, Y
Y = bound Mb / total Mb
= [O2]/(Kd+[O2]) (Kd also = P50)
Hyperbolic curve!
Intracellular pO2 is ______ than pO2 in capillaries
Less, therefore saturation in cells can vary depending on the environment it is in, and the amount that can be taken up is represented by ΔY.
Hemoglobin
Homotetrameric, with α1α2β1β2 subunits bound to four different heme groups. Kinda similar to four bound myoglobins but different.
Relaxed hemoglobin
Oxygenated, broken ionic interactions result in high affinity for O2.
Tense hemoglobin
Deoxygenated, low affinity
Favoured by salt bridges
Allosteric effectors of hemoglobin
Salt bridges involving histidine use H+ conditions.
Protonation favours T, adding acidic increases causing lower affinity for O2 to drop it off.
Deprotonation supports R.
Encourages O2 delivery.
Bohr effect
Low pH stabilises the T state.
CO2 reacts with N terminus of hemoglobin
Bicarbonate, carbanolates the Hb so CO2 is carried around. O2 affinity is lowered, stabilising the T state.
Right shift of Hb-O2 curve on affinity
Decreases affinity
BPG
Long term, only binds the T state and then stabilises it - rightward shift. Normal concentration = 5mmol/L.
Adaption to high altitudes is actually decreased but delivery is better due to bigger ΔY.
Fetal hemoglobin
α2γ2 subunits means that the Hb cannot bind BPG, increasing O2 affinity so that O2 transfers better from the placenta to foetus.
Molecular basis of SCA
Point mutation changes Glu to Val, acid to nonpolar amino acids, induces the hydrophobic effect and the protein aggregates. Destabilised means deoxygenated Hb polymerises into intracellular fibres that create the characteristic shape that causes RBCs to get stuck and break in the capillaries
Treatment of SCA
hydroxyurea: stimulates γ chain production so that there is no β chain present - no mutation in cells, and no anemia.
Other therapies are BM transplants and gene therapies.
