118 The Cell Language Theory: Connecting Mind and Matterb2861 The Cell Language Theory: Connecting Mind and Matter “6x9”In step 1 in Figure 3.29, the Electron Transfer Complex (ETC) catalyzes
the separation of electrons and protons, storing a part of the free energy
released from the redox (reduction–oxidation) reaction as conformons
(denoted by the symbol *). In step 2, the energized ETC interact with a
hypothetical intramembrane protein acting as a proton pump (and hence
called Proton Transfer Complex (PTC), or transprotonase, in analogy to
transhydrogenase), donating two protons to the matrix (or the lower) side of
PTC and abstracting two protons from the cytosolic (or the upper) side,
resulting in a depolarized (or de-energized) ETC and a polarized and thus
energized PTC (as indicated by the movement of the conformon * from ETC
to PTC). In step 3, the polarized and energized PTC utilizes its conformons
to actively pump protons out from the matrix space to the intermembrane
space to create a pH gradient and a membrane potential (as in the chemios-
motic hypothesis). Alternatively, the energized PTC can transfer its confor-
mons (presumably via asymmetric protonation–deprotonation reactions as
in step 2) to the oligomycin-sensitive ATP synthase (OSA) (which can be
identified with the F 1 portion of the F 0 F 1 -ATPase (see the figure in the upper
right-hand corner in Figure 3.35), leading to the de-energization of PTC and
the energization of OSA as shown in step 4. In step 5, a part of the confor-
mons stored in OSA is thought to be used to phosphorylate the AMP bound
to the basepiece of OSA, 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 mem-
brane potential generated in step 3. All the steps included in Figure 3.29 are
supported by experimental data on the actions of the inhibitors and uncou-
plers 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.
Little was known about the internal structure of the oligomycin-
sensitive ATPase (OSA) when Figure 3.29 was constructed in 1972–77.
During the last four decades, high-resolution X-ray structures of OSA
have been revealed [163, 205, 212, 214], and the mechanisms shown in
Figure 3.29 now need to be updated as follows:b2861_Ch-03.indd 118 17-10-2017 11:46:39 AM