Mitchell chemiosmotic theory

P. Mitchell (Bodmin, Cornwall) contributions to the understanding of biological energy transfer through the formulation of the chemiosmotic theory. 

Mitchell s chemiosmotic theory postulates that the energy from oxidation of components in the respiratory chain is coupled to the translocation of hydrogen ions (protons, H+) from the inside to the outside of the inner mitochondrial membrane. The electrochemical potential difference resulting from the asymmetric dis-... 

P. Mitchell (Nobel Prize for Chemistry, 1978) explained these facts by his chemiosmotic theory. This theory is based on the ordering of successive oxidation processes into reaction sequences called loops. Each loop consists of two basic processes, one of which is oriented in the direction away from the matrix surface of the internal membrane into the intracristal space and connected with the transfer of electrons together with protons. The second process is oriented in the opposite direction and is connected with the transfer of electrons alone. Figure 6.27 depicts the first Mitchell loop, whose first step involves reduction of NAD+ (the oxidized form of nicotinamide adenosine dinucleotide) by the carbonaceous substrate, SH2. In this process, two electrons and two protons are transferred from the matrix space. The protons are accumulated in the intracristal space, while electrons are transferred in the opposite direction by the reduction of the oxidized form of the Fe-S protein. This reduces a further component of the electron transport chain on the matrix side of the membrane and the process is repeated. The final process is the reduction of molecular oxygen with the reduced form of cytochrome oxidase. It would appear that this reaction sequence includes not only loops but also a proton pump, i.e. an enzymatic system that can employ the energy of the redox step in the electron transfer chain for translocation of protons from the matrix space into the intracristal space. 

In Mitchell s earliest physicochemical formulations of the chemiosmotic theory, any involvement of the membrane across which the proton gradient was established received little attention. Between 1961... 

Peter Mitchell Great Britain chemiosmotic theory... 

This mechanism was first described as the chemiosmotic theory of ATP generation, or the Mitchell hypothesis. 

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 reaction mechanism of cytochrome bc complex is known as the proton motive Qcycle originally proposed by Peter Mitchell (Mitchell, 1976). This mechanism is the basis of his chemiosmotic theory for which he was awarded the Nobel prize in 1978. Since then, the enzyme has been characterized extensively using various techniques. Redox centers have been characterized spectroscopically (for review, see Trumpower and Gennis, 1994), electron transfer pathways have been determined using kinetic experiments with specific inhibitors (De Vries 1986 Zhu et al., 1984), and the positions of quinone binding sites and redox centers have been determined using biochemical and mutational analysis (for review, see Esposti et al, 1993 Brasseur et al, 1996). As a result of these efforts, the latest modified Qcycle has been widely accepted by researchers in the field (for reviews, see Crofts et al, 1983 Trumpower, 1990 Berry et al, 2000). 

Mitchell s chemiosmotic theory [68-70] is generally accepted (see reviews in Refs. 5,37 and 71), though a large number of important details are still undefined, including the mechanism of action of the ATP synthase itself, and the ratio of ATP formed to electron transported. 

The molecular details of this principle, e.g, the mechanism of proton translocation by the respiratory complexes, and the pathways of the proton circuitry connecting respiration to phosphorylation, are still open questions [8,14,15]. Mitchell s chem-iosmotic theory [13,16], though instrumental in the development of the dogma, stresses such mechanistic details [17,18], Hence, it is a special case of the more general dogma, which also encompasses the early proposals by Williams [19,20] of protonic coupling within the membrane. The latter idea originally caused less impact than the chemiosmotic theory, probably due to its lack of details amenable to experimental scrutiny (but see, e.g.. Refs. 21,22). 

Proton motive ATP synthesis in FqF, liposomes (Fig. 5.1, Table 5.4) and AjEtH -driven translocation through Fg [6] strongly supported Mitchell s chemiosmotic theory described in the previous series of Comprehensive Biochemistry [108]. The molecular mechanism of function of FgF, was not predicted by this theory, but it has been elucidated by new methods. For example, the presence of X-P was demonstrated in... 

In this chapter, we will describe the composition of the phosphorylating enzyme of chloroplasts as determined by SDS-gel electrophoresis and its structure as revealed by electron microscopy. These studies led to a preliminary model for the chloroplast ATP synthase. The remainder of the chapter will be devoted to two main topics (photo)phosphorylation powered by proton translocation as described by Mitchell s chemiosmotic theory V and recent investigations of the structure and function of the phos-phorylating enzyme in relation to Paul Boyer s binding-change mechanism and a model involving... 

According to Mitchell s chemiosmotic theory, photophosphorylation is driven by energy derived from electron transfer coupled to proton translocation. The results of postillumination discussed in the previous section further supports the notion that a proton gradient is the driving force for phosphorylation. It is therefore possible in principle that a similar proton gradient produced by artificial means might also be able to drive phosphorylation in a chloroplast membrane, entirely in the dark, i. e., without the aid of photo-induced electron transport. Such a scheme was indeed realized by the so-called acid-bath ATP-forma-tion demonstrated by Jagendorf and Uribe " in 1966. 

Figure 18-13 Principal features of Mitchell s chemiosmotic theory of oxidative phosphorylation.

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