Theory chemiosmotic

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

Nicholls, D.G. (1982). Bioenergetics An Introduction to Chemiosmotic Theory. London U.K. Academic Press. 

THE CHEMIOSMOTIC THEORY EXPLAINS THE MECHANISM OF OXIDATIVE PHOSPHORYLATION... 

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-... 

The respiratory chain contains components organized in a sided manner (transverse asymmetry) as required by the chemiosmotic theory. 

Figure 12-8. Principles of the chemiosmotic theory of oxidative phosphorylation. The main proton circuit is created by the coupling of oxidation in the respiratory chain to proton translocation from the inside to the outside of the membrane, driven by the respiratory chain complexes I, III, and IV, each of which acts as a protonpump. Q, ubiquinone C, cytochrome c F Fq, protein subunits which utilize energy from the proton gradient to promote phosphorylation. Uncoupling agents such as dinitrophenol allow leakage of H" across the membrane, thus collapsing the electrochemical proton gradient. Oligomycin specifically blocks conduction of H" through Fq.

The Chemiosmotic Theory Can Account for Respiratory Control and the Action of Uncoupiers... 

This potential, or protonmotive force as it is also called, in turn drives a number of energy-requiring functions which include the synthesis of ATP, the coupling of oxidative processes to phosphorylation, a metabohc sequence called oxidative phosphorylation and the transport and concentration in the cell of metabolites such as sugars and amino acids. This, in a few simple words, is the basis of the chemiosmotic theory linking metabolism to energy-requiring processes. 

D. G. Nicholls, Bioenergetics An Introduction to the Chemiosmotic Theory, Academic Press,... 

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... 

For a proton motive force to develop, the inner mitochondrial membrane must have a very low permeability to protons so that they do not simply flow back down their concentration gradient and dissipate the high-energy state. Indeed, support for the chemiosmotic theory was first provided by the fact that the rate of the leak of protons back across the membrane is very low, although it can occur under special conditions. When it occurs, it is known as uncoupling (Box 9.2). 

Peter Mitchell Great Britain chemiosmotic theory... 

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

Chemiosmotic theory provides the intellectual framework for understanding many biological energy transductions, including oxidative phosphorylation and photophosphorylation. 

Chemiosmotic theory readily explains the dependence of electron transfer on ATP synthesis in mitochondria. When the flow of protons into the matrix through the proton channel of ATP synthase is blocked (with oligomycin, for example), no path exists for the return of protons to the matrix, and the continued extrusion of protons driven by the activity of the respiratory chain generates a large proton gradient. The proton-motive force builds up until the cost (free energy) of pumping... 

A prediction of the chemiosmotic theory is that, because the role of electron transfer in mitochondrial ATP synthesis is simply to pump protons to create the electrochemical potential of the proton-motive force, an artificially created proton gradient should be able to replace electron transfer in driving ATP synthesis. This has been experimentally confirmed (Fig. 19-20). Mitochondria manipulated so as to impose a difference of proton concentration and a separation of charge across the inner membrane synthesize ATP in the absence of an oxidizable substrate the proton-motive force alone suffices to drive ATP synthesis. 

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

A fundamental postulate of the chemiosmotic theory is the presence of an oriented ATP synthase that utilizes the Gibbs energy difference of the proton gradient to drive the synthesis of ATP (Fig. 18-9). 

A consequence of the chemiosmotic theory is that there is no need for an integral stoichiometry between protons pumped and ATP formed or for an integral P / O ratio. There are bound to be inefficiencies in coupling, and Ap is also used in ways other than synthesis of ATP. 

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