Figure 1-1.
Oxygen saturation curves for hemoglobin and myoglobin.
to one HbA subunit increases the affinity of binding to other subunits in the
tetramer, thereby shifting the equilibrium between oxy and deoxy forms. The
net effect of this cooperativity is that HbA is able to release oxygen, whereas
Mb globin would be most saturated with oxygen at the partial pressure of oxy-
gen normally found in resting peripheral tissues. The quaternary structure of
HbA also allows it to respond to
2,3-bisphosphoglycerate, carbon dioxide,
and hydrogen ion, all of which are heterotropic negative allosteric effec-
tors of oxygen binding.
Sickle cell anemia
results from the nonconservative substitution of
for glutamate at residue 6 (Val-6) in the p-chain of hemoglobin.
mutated hemoglobin is called HbS. The intrinsic oxygen binding properties of
HbA and HbS are the same, however, the
solubility of deoxy HbS is reduced
because of exposure of
at the
surface of the P-chain.
Since hemoglobin
is present at very high concentrations in the red blood cell,
deoxy HbS will
precipitate inside the cell.
The precipitate takes the form of elongated fibers
because of the association of complementary hydrophobic surfaces on the P- and
a-chains of deoxy HbS. At oxygen saturations found in arterial blood, the oxy
HbS predominates and HbS does not precipitate because Val-6 of the P-chain
is not exposed to the surface.
The tendency for deoxy HbS to precipitate is why clinical manifestations of
sickle cell anemia are brought on by
and why
treatment includes
administration of oxygen.
The stiff fibrous precipitate causes the red blood
cell to deform into the characteristic sickle shape and makes the normally mal-
leable cell susceptible to hemolysis.
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