Chemiosmotic model

Louie TM, WW Mohn (1999) Evidence for a chemiosmotic model of dehalorespiration in Desulfomonile tiedjei DCB-1. J Bacterial 181 40-46. 

The chemiosmotic model, proposed by Peter Mitchell, is the paradigm for this mechanism. According to the model Peter Mltchel1,... 

Before the general acceptance of the chemiosmotic model for oxidative phosphorylation, the assumption was that the overall reaction equation would take the following form ... 

A clear and critical account of the evolution of the chemiosmotic model. 

The demise of the famous Hodgkin-Huxley theory of nerve conductance brings to mind other Nobel prizes in electrochemically related areas. In 1959 Heyrovsky was recognized for a new analytical method, and this polarography has been the origin of many modem methods of electroanalysis. The award for Nobel Prize to Mitchell in 1978 (for a chemiosmotic model of membrane function) and metabolism seems to have been based on a lack of awareness of a simpler, clearer (prior) model by Williams for interpreting the same functions. The award to Marcus in 1992 for the theory of redox reactions (1956) seems to have lacked awareness of an earlier publication by Weiss that described similar ideas. 

A competing model called the chemiosmotic model was suggested by Mitchell in 1961 and won a Nobel prize. The physical events that which Mitchell s theory implies are less consistent with modem concepts of interfacial charge transfer than those of Williams, which do indicate interfacial charge transfer. 

The chemiosmotic model requires that flow of electrons through the electron-transport chain leads to extrusion of protons from the mitochondrion, thus generating the proton electrochemical-potential gradient. Measurements of the number of H+ ions extruded per O atom reduced by complex IV of the electron-transport chain (the H+/0 ratio) are experimentally important because the ratio can be used to test the validity of mechanistic models of proton translocation (Sec. 14.6). 

In the chemiosmotic model, as first developed by Mitchell in the early 1960 s, proton translocation arises from transfer of electrons from an (H + + e ) carrier (such as FMNH2) to an electron carrier (such as an iron-sulfur protein), with expulsion of protons to the outer compartment of the inner mitochondrial membrane. This process is followed by electron transfer to an (H+ + e ) carrier, with uptake of protons from the matrix. In this model, the electron-transport chain is organized into three such loops, as shown in Fig. 14-5. 

For the MNET description we take the presently most widely accepted model for this process as a basis the chemiosmotic model of Mitchell [37]. It comprises three elemental reactions in the mitochondrial membrane (apart from the translocators bringing the substrates to the active site of the enzymes acting upon them) (cf.. Fig. 1.3). The membrane itself is supposed to have a certain permeability to protons. The ATP synthase is a reversible pump, that pumps a certain number of protons... 

The complete set of equations, describing oxidative phosphorylation according to the chemiosmotic model, is as follows ... 

Mitchell suggested that the free energy release associated with electron transport and ATP synthesis is coupled by the protonmotive force created by the ETC. (The term chemiosmotic emphasizes that chemical reactions can be coupled to osmotic gradients.) An overview of the chemiosmotic model as it operates in the mitochrondion is illustrated in Figure 10.12. 

The chemiosmotic model, proposed by Peter Mitchell, is the paradigm for this mechanism. According to the model (Fig. 19-17), the electrochemical energy inherent in the difference in proton concentration and separation of charge across the inner mitochondrial membrane—the proton-motive force—drives the synthesis of ATP as protons flow passively back into the matrix through a proton pore associated with ATP synthase. To emphasize this crucial role of the proton-motive force, the equation for ATP synthesis is sometimes written... 

Chemiosmotic model of ATP synthesis. The chemiosmotic model explains how energy from transport of electrons to O2 is transformed into the high-energy phosphate bond of ATP (see Fig. 21.1). Basically, the electron transport chain contains three large protein complexes (I, III, and IV) that span the inner mitochondrial membrane. As electrons pass through these complexes in a series of oxidation-reduction reactions, protons are transferred from the mitochondrial matrix to the cytosolic side of the inner mitochondrial membrane. 

Describe the chemiosmotic model of oxidative phosphorylation and relate experimental evidence that only the proton-motive force links the respiratory chain and ATP synthesis. 

Which of the following experimental observations provide evidence supporting the chemiosmotic model of oxidative phosphorylation ... 

FIGURE 19. (a) Chemiosmotic model of phosphorylation, (b) Electrodic model of phosphorylation. 

The mosaic nonequilibrium thermodynamics formulation of oxidative phosphorylation uses the chemiosmotic model as a basis, besides assuming that the membrane has certain permeability to protons, and that the ATP synthase is a reversible pump coupled to the hydrolysis of ATP. It is assumed that the reversibility of the reactions allows the coupled transfer of electrons in the respiratory chain for the synthesis of ATP, and the proton gradient across the inner mitochondrial... 

Of particular interest to us are the membrane proteins, numbered I-V. Four of them are part of the electron transport chain in accordance with the chemiosmotic model. FT in the chains is driven by the energy of food or by photosynthesis. Protons are pumped across the membrane to a more acid location. This is done in Complex I, Complex III, and Complex IV. Complex II is used in reduction of ubiquinone to ubiquinol. Another molecule of this type is Complex V, an ATP synthase where ATP is synthesized from ADP and P, as just mentioned. This complex does not have any electron transport chain. 

The simplest possible version of the chemiosmotic model visualizes the membrane in a fluid moasaic structure in which the various enzyme complexes are freely diffusable and energetically coupled through the circulation of protons.-No barrier for the diffusion of protons is assumed between the aqueous bulk compartments,facing both sides of the membrane,and the proton releasing or accepting sites of the proton translocating enzymes. 

In their work on oxidative phosphorylation in mitochondria, Baum et al.(1971) pioneered the use of double inhibitor titration of electron transfer reactions and of ATPase as an approach for the study of the interaction between energy transducers. In the chemiosmotic model, the coupling between two enzyme complexes is mediated by the "delocalized" protons, so that if one of the two transducers is kinetically limiting the overall rate, the inhibition of the other complex should not influence the overall velocity of the process. 

---