Oxidative phosphorylation thermodynamics

One view to explain different P/O ratios for different classes of organisms is to consider variability in both the molecular mechanism as well as the stoichiometry of proton transport and ATP synthesis with the source of the enzyme [67]. However, considering our molecular mechanism and the energetics of the oxidative phosphorylation process, we believe that a universality in the mechanistic, kinetic and thermodynamic characteristics of the system is operative. 

Nath S (1994) A fundamental thermodynamic principle for conpling in oxidative phosphorylation. 16th Int Congr Biochemistry and Molecular Biology, New Delhi, India, vol II,... 

How is a concentration gradient of protons transformed into ATP We have seen that electron transfer releases, and the proton-motive force conserves, more than enough free energy (about 200 lcJ) per mole of electron pairs to drive the formation of a mole of ATP, which requires about 50 kJ (see Box 13-1). Mitochondrial oxidative phosphorylation therefore poses no thermodynamic problem. But what is the chemical mechanism that couples proton flux with phosphorylation ... 

A quantitative description of oxidative phosphorylation within the cellular environment can be obtained on the basis of nonequilibrium thermodynamics. For this we consider the simple and purely phenomenological scheme depicted in Fig. 1. The input potential X0 applied to the converter is the redox potential of the respiratory substrates produced in intermediary metabolism. The input flow J0 conjugate to the input force X0 is the net rate of oxygen consumption. The input potential is converted into the output potential Xp which is the phosphate potential Xp = -[AG hoS -I- RT ln(ATP/ADP P,)]. The output flow Jp conjugate to the output force Xp is the net rate of ATP synthesis. The ATP produced by the converter is used to drive the ATP-utilizing reactions in the cell which are summarized by the load conductance L,. Since the net flows of ATP are large in comparison to the total adenine nucleotide pool to be turned over in the cell, the flow Jp is essentially conservative. 

In order to extract the maximal energy out of the available foodstuff oxidative phosphorylation should operate at the state of optimal efficiency in vivo. Since a zero as well as an infinite load conductance both lead to a zero efficiency state, obviously there must be a finite value of the load conductance permitting the operation of the energy converter at optimal efficiency. For linear thermodynamic systems like the one given in equations (1) and (2) the theorem of minimal entropy production at steady state constitutes a general evolution criterion as well as a stability criterion.3 Therefore, the value of the load conductance permitting optimal efficiency of oxidative phosphorylation can be calculated by minimizing the entropy production of the system (oxidative phosphorylation with an attached load)... 

In order to obtain a more intuitive insight into the mechanism of thermodynamic buffering we calculated the effects of thermodynamic buffering on the entropy production of the system. The entropy production of oxidative phosphorylation with an attached load is given in equation (8). A convenient way to introduce the contribution of the adenylate kinase reaction to this system is to consider L/ as an overall load conductance embracing the effects of the adenylate kinase reaction as well as the effects of the true extrinsic load conductance of the irreversible ATP utilizing... 

Here we present a computational model of mitochondrial electrophysiology and oxidative phosphorylation is based on the models of one of the authors [13, 14] and Wu et al. [212], The processes illustrated in Figure 7.9 are modeled based on the electrophysiology modeling approach outlined in Section 7.3. Thermodynamic constants for the transport reactions are computed from thermodynamic data tabulated in Table 6.1. 

The control coefficients can be determined by the linear nonequilibrium thermodynamics formulation. Schuster and Westerhoff (1999) provide a simple example for the coupled processes of oxidative phosphorylation with slipping enzymes, for which a representative dissipative function is... 

Stucki (1980, 1984) applied the linear nonequilibrium thermodynamics theory to oxidative phosphorylation within the practical range of phosphate potentials. The nonvanishing cross-phenomenological coefficients Ly(i v /) reflect the coupling effect. This approach enables one to assess the oxidative phosphorylation with H+pumps as a process driven by respiration by assuming the steady-state transport of ions. A set of representative linear phenomenological relations are given by... 

The second law of thermodynamics states that entropy production or exergy loss as a consequence of irreversibility is always positive. A representative overall dissipation function for oxidative phosphorylation is... 

Gain ratio 17 r can be calculated at a reference force ratio, such as xopt, which is a natural steady-state force ratio of oxidative phosphorylation. This is seen as a result of the adaptation of oxidative phosphorylation to various metabolic conditions and also as a result of the thermodynamic buffering of reactions catalyzed by enzymes. The experimentally observed linearity of several energy converters operating far from equilibrium may be due to enzymatic feedback regulations with an evolutionary drive towards higher efficiency. 

Within the framework of the theory of dissipative structures, thermodynamic buffering represents a new bioenergetics regulatory principle for the maintenance of a nonequilibrium conditions. Due to the ATP production in oxidative phosphorylation, the phosphate potential is shifted far from equilibrium. Since hydrolysis of ATP drives many processes in the cell, the shift inXp to far from equilibrium results in a shift of all the other potentials into the far from equilibrium regime. 

The cytochrome c oxidase reaction encompasses the so-called third site of oxidative phosphorylation. There is no doubt that oxidation of cytochrome c by dioxygen results in generation of pmf. Cytochrome oxidase was long believed to do so simply by catalysing transmembranous electron transfer, with uptake of the protons required in reduction of Oj to water from the M phase. Such a function is thermodynamically equivalent to translocation of one proton per transferred electron, although no protons appear on the C side [8]. 

The electrons in QHt at a higher redox potential than those in HiO. Recall that, in oxidative phosphorylation, electrons flow from ubiquinol loan acceptor, O7, that is at a lower potential. Photosystem II drives the reaction in a thermodynamically uphill direction by using the free energy of light. 

Skill 22.1 Using chemical principles (including thermodynamics) to analyze important biochemical processes (e.g., synthesis, degradation, electron transport, oxidative phosphorylation)... 

Approximately 90 to 95% of the oxygen we consume is used by the terminal oxidase in the electron transport chain for ATP generation via oxidative phosphorylation. The remainder of the O2 is used directly by oxygenases and other oxidases, enzymes that oxidize a compound in the body by transferring electrons directly to O2 (Fig. 19.12). The large positive reduction potential of O2 makes all of these reactions extremely favorable thermodynamically, but the electronic structure of O2 slows the speed of electron transfer. These enzymes, therefore, contain a metal ion that facilitates reduction of O2. 

Van der Meer et al. [59] have described the regulation of mitochondrial respiration on the basis of the principles of irreversible thermodynamics. According to these authors, and thus in contrast to the view of Holian et al. [53], the entire system of oxidative phosphorylation in the hepatocyte is displaced from equilibrium. They observed a linear relationship between the rate of oxygen consumption and the affinity of the entire oxidative pho.sphorylation system, a term which includes the cytosolic phosphate potential, the mitochondrial NADH/NAD ratio and the partial pressure of oxygen. They concluded that the adenine nucleotide translocator may be a rate-limiting step in cellular oxidative phosphorylation. 

---