The Conformon - Molecular Theory of the Living Cell - page 243

in the cytosol provides the thermodynamic driving force and in the reverse direction
when the high luminal Ca ++ ion concentration relative to that in the cytosolic side
provides the thermodynamic driving force.
The essence of the model shown in Figs. 8.7 and 8.8 is the synchronization
(or long-range correlations) of the fast ATP hydrolytic electronic transitions occur-
ring in the C domain with the slow Ca ++ ion positional changes that occur within the
T domain separated from the C domain by at least 40-50 ˚ (Toyoshima et al.
2000). One way to avoid the action-at-a-distance problem that plagued Newtonian
mechanics is to postulate that these two events are coupled through the transfer of
conformons from the ATP processing sites in the C domain to the Ca ++ -binding
sites in the T domain through the structural link that connects these two domains
(symbolized by “~” in Fig. 8.7 ), again obeying the generalized Franck-Condon
principle implemented by the pre-fit mechanisms (Sect. 7.1.3 ). In other words, the
two domains of the calcium ion pump are correlated or coupled via conformon
exchanges just as quarks in hadrons (i.e., protons, neutrons and pions) are coupled
through the exchange of gluons (Han 1999). Conformons can be generated in the
Ca ++ -binding sites in the T domain which are then transferred to the ATP-
processing sites in the C domain, when the thermodynamic driving force is
provided by the Ca ++ ion gradient, high in the luminal side and low in the cytosolic
side. This conclusion is mandated by the principle of microscopic reversibility,
Statement 8.15 (Hine 1962).
8.7 The Conformon Hypothesis of Energy-Coupled
Processes in the Cell
The cell is composed of three main classes of material entities - biopolymers (i.e.,
DNA, RNA proteins, etc.), metabolites (e.g., glucose, pyruvate, NADH, ATP, O 2 ,
CO 2 ,H 2 O, and etc.) and inorganic ions (e.g., H + ,Na + ,K + ,Ca ++ , etc.). The interior
space of the cell is so crowded with these molecular entities that changing the
concentration of any one component at a given locus within the cell may affect the
chemical activities of other components in distant locations due to the so-called
crowding effects or macromolecular crowding effects (Minton 2001; Pielak 2005;
McGuffee and Elcock 2010) (see Figs. 12-28).
All these intracellular molecular entities are in constant motions under physio-
logical temperatures, and these motions can be divided into three categories - (1)
up-hill motions, also called energy-requiring or endergonic processes (e.g., ion
pumping, molecular motor movement, synthesis of ATP); (2) down-hill motions ,
also called energy-dissipating or exergonic processes (e.g., diffusion of ions across a
membrane along their concentration gradients, ATP hydrolysis under physiological
conditions); and (3) random (or stochastic ) motions (e.g., thermal fluctuations or
Brownian motions of biopolymers and collisions among molecules). Random
motions lack any regularity but stochastic motions can exhibit regularities although