Chemiosmotic coupling oxidative phosphorylation

Mechanism of Oxidative Phosphorylation Chemiosmotic Coupling (Figure 15.15)... 

Chemiosmotic coupling is the mechanism most widely used to explain the manner in which electron transport and oxidative phosphorylation are coupled to one another. In this mechanism, the proton gradient is directly linked to the phosphorylation process. The way in which the proton gradient leads to the production of ATP depends on ion channels through the inner mitochondrial membrane these channels are a feature of the structure of ATP synthase. Protons flow back into the matrix through proton channels in the Fq part of the ATP synthase. The flow of protons is accompanied by formation of ATP, which occurs in the Fj unit. 

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.

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. 

Mitchell, P. (1966). Chemiosmotic Coupling in Oxidative and Photosynthetic Phosphorylation. Glynn Research, Bodmin, Cornwall, U.K. 

In many instances, substrate phosphorylation is not coupled to oxidation of the electron donor source by the bacteria therefore, growth will result from oxidative phosphorylation with electrons energizing the plasma membrane for ATP production according to the chemiosmotic system. A list of bacteria displaying dissimilatory reduction where growth is coupled to reduction of metaPmetalloid electron acceptors is given in Table 16.4. 

Oxidative phosphorylation is the name given to the synthesis of ATP (phosphorylation) that occurs when NADH and FADH2 are oxidized (hence oxidative) by electron transport through the respiratory chain. Unlike substrate level phosphorylation (see Topics J3 and LI), it does not involve phosphorylated chemical intermediates. Rather, a very different mechanism was proposed by Peter Mitchell in 1961, the chemiosmotic hypothesis. This proposes that energy liberated by electron transport is used to create a proton gradient across the mitochondrial inner membrane and that it is this that is used to drive ATP synthesis. Thus the proton gradient couples electron transport and ATP synthesis, not a chemical intermediate. The evidence is overwhelming that this is indeed the way that oxidative phosphorylation works. The actual synthesis of ATP is carried out by an enzyme called ATP synthase located in the inner mitochondrial membrane (Fig. 3). 

In the chemiosmotic theory for oxidative phosphorylation (Chap. 14), electron flow in the electron-transport chain is coupled to the generation of a proton concentration gradient across the inner mitochondrial membrane. Derive an expression for the difference in electrochemical potential for a proton across the membrane. 

ATP formation coupled to electron flow in mitochondria is usually called oxidative phosphorylation. Because electron flow involves both reduction and oxidation, more appropriate names are respiratory phosphorylation and respiratory-chain phosphorylation, terminology that is also more consistent with photophosphorylation for ATP formation in photosynthesis. As with photophosphorylation, the mechanism of oxidative phosphorylation is not yet fully understood in molecular terms. Processes like phosphorylation accompanying electron flow are intimately connected with membrane structure, so they are much more difficult to study than are the biochemical reactions taking place in solution. A chemiosmotic coupling mechanism between electron flow and ATP formation in mitochondria is generally accepted, and we will discuss some of its characteristics next. 

Fig. 1.3. A scheme of oxidative phosphorylation according to the chemiosmotic coupling hypothesis.

The inconsistency between experiment and prediction must lead to the rejection of the model used to describe the system. In the case of oxidative phosphorylation this has led to a refined model, in which the chemiosmotic coupling is visualized as taking place within units of one (or a few) respiratory chain(s) plus ATP synthase, while the pumped protons have only limited access to the bulk phase inside and/or outside the mitochondrion [42]. This more refined model can again be tested by deriving from it flux-force relations according to the MNET approach. A discussion of the refined model can be found in Ref. 43. 

Two major ATP synthesizing reactions in living organisms are oxidative phosphorylation and photophosphorylation. Both reactions take place in H -ATPase (FqF,), which is driven by an electrochemical potential difference of protons across the biomembrane, as predicted by Mitchell [1]. In Racket s laboratory, ATPases related to oxidative phosphorylation were prepared, but their relationship to Mitchell s chemiosmotic hypothesis [1] was not described [2], Later, an insoluble ATPase (H -ATPase) was shown to translocate protons across the membrane when it was reconstituted into liposomes [3], H -ATPase was shown to be composed of a catalytic moiety called F, (coupling factor 1) [4], and a membrane moiety called Fq [5], which confers inhibitor sensitivity to F,. F was shown to be a proton channel, which translocates down an electrochemical potential gradient across the membrane when Fg is reconstituted into liposomes (Fig. 5.1) [6]. Thus, -ATPase was called FqFj or ATP synthetase. 

Nicholls, D.G., Cannon, B., Grav, H.J. and Lindberg, O. (1974) In Dynamics of Energy-Transducing Membranes (Emster, L., Estabrook, R.W. and Slater, E.C., eds.) pp. 529-537, Elsevier, Amsterdam. Mitchell, P. (1966) Chemiosmotic Coupling in Oxidative and Photosynthetic Phosphorylation. Glynn Res. Ltd., Bodmin, Cornwall, England. 

The anisotropic organization of electron carriers across the membrane accounts for the vectorial transport of protons from the inside to the outside of the membrane, which occurs with the passage of electrons. The coupling of this proton gradient to a proton-translocating ATP synthase (also known as ATP synthetase) accounts for the chemiosmotic coupling in oxidative phosphorylation. 

The answer is b. (Murray, pp 123-148. Scriver, pp 2367-2424. Sack, pp 159-115. Wilson, pp 287-3111) The chemiosmotic hypothesis of Mitchell describes the coupling of oxidative phosphorylation and electron transport. The movement of electrons along the electron transport chain allows protons to be pumped from the matrix of the mitochondria to the cytoplasmic side. The protons are pumped at three sites in the electron transport chain to produce a proton gradient. When protons flow back through proton channels of the asymmetrically oriented ATPase of the inner mitochondrial membrane, ATP is synthesized. 

Oxidative phosphorylation is the mechanism by which electron transport is coupled to the synthesis of ATP. According to the chemiosmotic theory, the creation of a proton gradient that accompanies electron transport is coupled to ATP synthesis. 

Mitchell, P., Chemiosmotic coupling in oxidative and photosynthetic phosphorylation, Biol. Rev. Camb. Philos. Soc., 1966, 41, 445-502. WiKSTEOM, M.K., Proton pump coupled to cytochrome c oxidase in mitochondria. Nature, 1977, 266, 271-273. 

See also Electron Transport, P/O Ratio, Chemiosmotic Coupling, Integrity of Mitochondrial Membranes, Uncoupling ETS and Oxidative Phosphorylation, The FIFO Complex, Oxidation as a Metabolic Energy Source (from Chapter 12)... 

In 1961, Peter Mitchell proposed the now widely accepted chemiosmotic coupling hypothesis to explain ATP synthesis as a result of electron transport (ETS) and oxidative phosphorylation. It consists of the following principles ... 

See also Chemiosmotic Coupling, Oxidative Phosphorylation, Uncoupling ETS and Oxidative Phosphorylation, Respiratory Control... 

Fillingame, R. The Proton-Translocating Pumps of Oxidative Phosphorylation. Ann. Rev. Biochem. 49, 1079-1114 (1980). [A review of chemiosmotic coupling.]... 

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