Oxidative phosphorylation, optimization

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)... 

Let us first consider the problem of an appropriate degree of coupling of oxidative phosphorylation in the cell. The solution to this question depends entirely on what output function is to be optimized. We might for example require a maximal net flow of ATP at optimal efficiency (Jp) opt. As is evident from Fig. 4 there is a unique degree of coupling qf, which corresponds to the maximum of this output function (see also Table I). Such a low value of the degree of coupling has never been experi-... 

Carrying out this optimization, we find that 18.667 ATP may be synthesized in this system for each glucose molecule consumed. The flux distribution at this optimal solution is illustrated in Figure 9.4. Here, 14.667 ATP/glucose are synthesized by the ATPase reaction of the oxidative phosphorylation system, 2 by glycolysis and 2 by the TCA cycle. 

This inequality means that the minimum dissipation and the natural steady state do not imply the optimal efficiency of oxidative phosphorylation. 

At the level flow, there is a load and hence a load conductance corresponding to the state of optimal efficiency between the static head and the level flow. The dissipation of oxidative phosphorylation with a coupled process (load) utilizing ATP is given as follows... 

For mitochondria, L33 is an overall phenomenological coefficient lumping together all the conductances of ATP-utilizing processes, while Lx x shows the conductance of phosphorylation. If these two coefficients match according to Eq. (11.111), then the natural steady state of oxidative phosphorylation is at the optimal efficiency. Stucki called Eq. (11.111) the condition of conductance matching of oxidative phosphorylation, and presented an experimental verification. 

The dissipation function at the state of optimal efficiency of oxidative phosphorylation is... 

Therefore, the low P/O ratios do not necessarily mean a poor performance of the oxidative phosphorylation. Similarly, the net rate of ATP synthesis at the optimal efficiency is given by... 

Optimal flow ratios are also a characteristic of oxidative phosphorylation, and may provide additional information on the relationships between the respiratory response and energy demand stimulation by ADP. Most metabolic processes in living cells are dynamic systems, and the behavior of flows may better reflect complex system mechanisms than do the models dependent on end-point measurements. For example, the ratio of ADP/O describes the state of the end-point capacity of oxidative phosphorylation based on the input flow of ADP. 

The optimum output power JxX )0Vt and the efficiency 0/, A, Tn)( nl are calculated from the plots of JxXx vs. x and JxXx r) vs. x, respectively. A transition from qv to q causes a 12% drop in output power (./,.V,) and a 51% increase in efficiency. For a favorable ATP production at optimal efficiency of oxidative phosphorylation, we should have q < 1. With the consideration of conductance matching, Stucki (1980) determined four production functions, which are given in Table 11.4. 

The rate of optimal efficiency of oxidative phosphorylation is not characterized by the exergy decrease, and the exergy loss at optimal efficiency is given by... 

Figure 11.7 shows that the values of 2 reach peak values higher than unity, and the exergy loss is not minimized at optimal efficiency of oxidative phosphorylation. The exergy loss is the lowest at the degree of coupling corresponding to the economical power output. 

For the optimal efficiency to occur at steady state, oxidative phosphorylation progresses with a load. Such a load. /L is an ATP-utilizing process in the cell, such as the transport of substrates. A load, which will make the steady state the optimal efficiency state, can be identified through the total exergy loss T,c... 

Transformation of pyruvate to acetyl-CoA is linked to glycolysis and to the Krebs cycle and oxidative phosphorylation. The pyruvate dehydrogenase complex (PDHc) catalyzes the oxidative decarboxylation of pyruvate and acetylation of coenzyme A (CoA) to acetyl-CoA. This enzyme has been viewed as a potential herbicide target [238], In the perspective of structural optimization of a potent new herbicide, He et al. synthesized a series of structures 307 [239-241], which were a priori designed to inhibit the PDHc. 

Stucki JW The optimal efficiency and the economic degrees of coupling of oxidative phosphorylation, Eur J Biochem 109(1) 269—283, 1980. 

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