Biomedical Engineering Reference
In-Depth Information
described to support this hypothesis and the classic one suggests that the Ca
2+
store must be
close enough to the plasma membrane to allow a constitutive protein-protein interaction
between capacitative Ca
2+
channels and IP
3
receptors [55]. Boyer's notion is accord with a
variety of binding experiments and is essentially consistent with Mitchell's chemiosmotic
hypothesis described in the following.
3. The Chemiosmotic Hypothesis
This hypothesis has been accepted as one of the most important contributions to the
twentieth century biology proposed by Mitchell in 1961 [56]. This hypothesis states that H
+
is
pumped to intermembrane space as electrons go through the electron transfer chain. As a
result, an electrical potential Δψ and a proton gradient ΔpH increase across the inner
membrane. The membrane potential and proton gradient are the proton-motive force (PMF)
which is responsible for driving the ATP synthesis (Figure 5). The following equation
obtained from Nernst equation describes calculation of ΔG associated with a proton gradient:
+
[
H
]
Δ
G
=
RT
ln
out
]
+
F
Δ
ψ
+
[
H
(1)
in
where [H
+
]
in
and [H
+
]
out
refer to the proton concentrations inside and outside the cellular
membrane respectively; F is Faraday's constant (96,485 J V
-1
mol
-1
); R is gas constant (8.31 J
mol
-1
K
-1
) and Δψ stands for potential difference across the membrane.
Proton leak
Membrane leak,
Cation cycles
Heat
Respiratory
system
Substrate
PMF
AT P
ATP synthesis
phosphorylation
Figure 5. The oxidative phosphorylation system. Substrates are oxidized in respiratory system, which,
in turn, produce the proton-motive force (PMF) across the mitochondrial cellular membrane. PMF is
subsequently used to drive ATP synthesis (phosphorylation), or membrance leak (proton leak).
3.2. Mechanism of Uncoupling of Oxidative Phosphorylation
Uncoupling of oxidative phosphorylation is an important method of determining the
nature of the chemiosmotic hypothesis and provides important information concerning the
