124 The Cell Language Theory: Connecting Mind and Matterb2861 The Cell Language Theory: Connecting Mind and Matter “6x9”(3) The respiratory enzyme system catalyzing Process 1 and the revers-
ible ATPase system catalyzing Process 2, Figure 3.34, are coupled
through the mediation of the common chemical species, i.e., the bulk
phase protons delocalized in the intermembrane space. The 1961 ver-
sion of the chemiosmotic model was modified in 1978 as shown in
Figure 3.32(b). The basic postulate that respiration and phosphoryla-
tion are coupled through the bulk phase, delocalized proton gradient
and attendant electrical potential has not changed, except that the
compartment in which water is formed changed from the L to the R
compartment, as pointed out in (2).
(4) The protons flowing through F 0 directly participate in ATP synthesis
in Complex V by abstracting hydroxide ions.
(5) The H+/2e- stoichiometry was postulated to be 1, 2, and 0 for
Complexes I, II, and IV, respectively, and the H+/ATP stoichiometry
was postulated to be 2, as shown in Figure 3.32(b).Of these five features, (1) and (2) are largely substantiated by experi-
ments such as those carried out by Racker and Stoeckenius in 1974 [206],
but such experimental results cannot rule out the possibility that the respi-
ration–phosphorylation coupling can alternatively be mediated by intra-
membrane protons of Williams [176] obeying the principle of Wyman’s
pseudolinkage (see Section 3.2.10) without implicating any bulk phase,
delocalized protons of Mitchell as assumed in the chemiosmotic model. In
fact, both these mechanisms, i.e., the extra-membrane proton- and intra-
membrane proton-mediated oxphos, may occur under different physiolog-
ical conditions depending on the metabolic needs of the cell as pointed out
in [7, pp. 60–61; 25, pp. 383–388]. For example, in tumor cells, the extra-
membrane proton-mediated ATP synthesis may occur catalyzed by the
F 1 F 0 -ATP synthase located on the plasma membrane (see Figure 3.33),
since it would help reducing the acidity of the cytoplasm of tumor cells.
Or the ATP-driven proton pump of mitochondria may be reversed driven
by the pH gradient generated by aerobic glycolysis in tumor cells (low in
the cytosol and high in the mitochondrial matrix space) [557, 558].
Feature (4) must now be judged invalidated by the experimental find-
ing that the protons flowing through the F 0 component of the F 1 F 0 –ATPb2861_Ch-03.indd 124 17-10-2017 11:46:42 AM