Biomedical Engineering Reference
In-Depth Information
Hill Model
Measure of
cooperativity
of O
2
binding relies on oxygen saturation of hemoglobin
that is determined by measurement of the partial pressure of oxygen in solution
using Hill cooperativity coefficient
n
(oxygen concentration is proportional to partial
pressure). Because the hemoglobin saturation curve does not satisfy the hyperbolic
relationship observed for myoglobin:
S
(
p
(
50
)
: oxygen
partial pressure of O
2
at which half of Hb molecules are in the oxy state), Hill
assumed the following equilibrium in 1913:
(
O
2
)=
p
O
2
/
(
p
O
2
+
p
(
50
)
)
n
O
2
−−−−→
Hb
+
←−−−−
Hb
(
O
2
)
n
.
The fractional saturation for the hypothetical reaction is given by:
p
O
2
p
O
2
+
[
Hb
(
O
2
)
n
]
S
O
2
=
]
=
.
(3.3)
p
n
(
[
Hb
(
O
2
)
n
]+[
Hb
)
50
Hill plot corresponds to the trace of log
[
S
O
2
/
(
1
−
S
O
2
)]
(i.e., ratio of oxyHb to
n
. At small and large values of
p
O
2
,
n
desoxyHb) vs. log
(
p
O
2
/
p
)
)
=
1, whereas in
(
50
the transition region of the relationship,
n
=
2
.
8.
chains tightly hold oxygen.
Diphosphoglycerate (DPG) of the anaerobic glycolysis pathway used by RBCs that
lack mitochondria to produce enough ATP binds to Hb between 2 deoxygenated
β
In tissues,
β
chains very easily lose O
2
,but
α
chains. Conformational change that results promotes oxygen release from
chains. In lung capillaries, (2,3)-DPG is expelled from Hb molecules.
39
α
Haldane and Bohr Effects
The
Haldane effect
states that deoxygenated Hb has a greater affinity for CO
2
than
does oxyhemoglobin. Oxygen loading and unloading assist CO
2
release and pickup
in lungs and tissues, respectively, and conversely.
The
Bohr effect
states that deoxygenated Hb has a greater affinity for H
+
than
does oxyhemoglobin. Oxygen loading and unloading assist H
+
delivery and capture
in lungs and tissues, respectively, and conversely.
The Bohr and Haldane effects are allosteric effects caused by binding of different
ligands at different Hb spots that generates Hb conformational changes, thereby
increasing and decreasing Hb affinity for O
2
in lung and the body's tissues,
respectively.
39
Life at high altitude increases (2,3)-DPG production in addition to mitochondrial concentrations
and erythropoietin and RBC production.
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