Biology Reference
In-Depth Information
chemiosmosis (see Steps 1-3) (Mitchell 1961, 1968). What distinguishes
the
conformon model
and the
chemiosmotic model
of oxidative phosphorylation
(see Sect.
11.6
) is that the former is rooted in the generalized Franck-Condon
principle (Sect.
2.2.3
) which has been found to account for not only oxidative
phosphorylation but also enzymic catalysis (Sect.
7.2
) and muscle contraction
(Fig.
11.34
). It is clear that the chemiosmotic hypothesis is inapplicable to both
enzymic catalysis and muscle contraction, because these two processes can occur
without any osmotic barrier, the essential requirement of chemiosmosis - the
conversion of chemical energy to osmotic energy. In other words, the chemiosmotic
hypothesis has little to say concerning the fundamental molecular mechanisms
underlying enzymic catalysis and muscle contraction.
In Step 1, the electron transfer complex (ETC) catalyzes the separation of
electrons and protons, storing a part of the free energy released from the redox
reaction as conformons (denoted by the symbol * ). In Step 2, the energized ETC
collides with a hypothetical intra-membrane protein acting as a proton pump
(and hence called proton transfer complex, PTC), and two protons are postulated
to be donated to the matrix (or the lower) side of PTC and two protons are thought to
be abstracted from the cytosolic (or the upper) side, resulting in a depolarized and
de-energized ETC and a polarized and energized PTC. In Step 3, the polarized PTC
utilizes its conformons to actively pump protons out from the matrix space to
the cytosolic space to create a pH gradient and a membrane potential (as in the
chemiosmotic hypothesis). Alternatively, the energized PTC can transfer its
conformons (via asymmetric protonation-deprotonation reactions as in Step 2) to
the mitochondrial ATP synthase (MAS), leading to the de-energization of PTC and
energization of MAS as shown in Step 4. In Step 5, a part of the conformons is used
to phosphorylate the AMP bound to the basepiece of MAS, and a second conformon
is postulated to be used to transfer the phosphoryl group from the ADP bound to the
basepiece of MAS to the ADP bound to the F
1
subunit (denoted as a circle) of MAS,
thus generating one ATP bound to MAS (see Step 6). In Step 7, this ATP is
exchanged for the ADP in the matrix space of mitochondria. Finally, in Step 8, the
ATP in the matrix compartment of mitochondria is actively transported out into the
cytosol, driven by the proton electrochemical gradient and membrane potential
generated in Step 3. All the steps included in Fig.
11.36
are supported by experi-
mental data on the actions of the inhibitors and uncouplers specific for them, except
Steps 2 and 7 whose inhibitors and uncouplers appear not to have been discovered
yet to the best of my knowledge.
11.6 Deconstructing the Chemiosmotic Hypothesis
The British biochemist, P. Mitchell (1920-1992), proposed the concept of
chemiosmosis
in 1960 (Mitchell 1961, 1968) in an attempt to explain how
mitochondria,
the powerhouse of the cell,
synthesize ATP from ADP and inorganic
phosphate, P
i
, utilizing the free energy supplied by the oxidation of substrates such as
