Biology Reference
In-Depth Information
energy. Without any
enzymologically realistic mechanisms
for coupling a down-
hill reaction (e.g., oxidation of NADH to NAD
+
) to an up-hill chemical reaction or
physical process (e.g., the vectorial movement of protons and asymmetric removal
of water or the hydroxyl group from the ATP synthesis center), structural asym-
metry alone cannot achieve or cause asymmetric metabolism. In fact to cause a
symmetry breaking in molecular processes without dissipating requisite free
energy is tantamount to violating the First Law of thermodynamics, because the
resulting gradients could be harnessed to do work, thereby producing energy.
2. According to the chemiosmotic coupling scheme, the protons generated from
respiration are extruded from the membrane phase (with volume V
M
) to the bulk
phase (with volume V
B
). As Williams (1969) correctly pointed out, this is an
energy-dissipating process because V
B
is much greater than V
M
. (The situation is
analogous to perfume molecules diffusing out of a perfume bottle into the vast
space of a dancing hall.) In addition, at least the same amount of free energymust be
dissipated during the proton-driven ATP synthetic step, because in order to bring
the protons back into the ATP synthesis center in the M phase (Fig.
11.37
), free
energy must be dissipated in the amount proportional to the volume ratio, V
B
/V
M
,
whichwould probably be greater than 10
9
. This ratio can be estimated bymeasuring
the areas occupied by the mitochondrial inner membrane relative to the cyto-
plasmic area in an electron micrograph of the cell and raising the resulting ratio to
the power of 3/2.
3. As indicated in (1), structural asymmetry is necessary but not sufficient for
effectuating asymmetric process or metabolism. In addition, it is critical for
the chemiosmotic hypothesis that the ATP synthesizing reaction center (see the
dotted circle in the lower box in Fig.
11.37
) be located
within
the M phase, not in
the R phase, since, in the latter case, the ATP synthesis cannot be driven by
any osmotic energy of the transmembrane proton gradient. However, the recent
X-ray crystallographic findings (Aksimentiev et al. 2004; Junge et al. 1997)
clearly demonstrate that the ATP synthase is located not in the M phase as
Mitchell assumed but outside the membrane phase attached to the proton
pumping structure (i.e., F
0
) in the M phase through a set of long polypeptide
chains (designated as
g
and
e
subunits).
4. It is generally accepted that, when ATP synthase catalyzes the formation of ATP
from ADP and P
i
driven by the proton gradient, the electrochemical energy of
proton gradient is first converted into the mechanical energy (in the form of
“torque,” i.e., the energy producing a rotatory motion) within F
0
, which is then
transmitted to F
1
(through the rotatory motion of the shaft composed of the
g
and
e
subunits) where the energy is utilized to release (or de-bind) ATP from F
1
(Aksimentiev et al. 2004). Thus, the sequence of events involved in the proton
gradient-driven synthesis of ATP can be depicted as follows (Scheme (
11.56
)):
1
Mechanical Energy of the
g
and
ð
Proton Gradient
Þ$
ð
Subunits
Þ
e
l
2
Chemical Energy of ATP
ð
Þ
(11.56)
