Chemiosmotic coupling hypothesis

The chemiosmotic coupling hypothesis, proposed by P. Mitchell, is the most attractive explanation, and many experimental observations now support this idea. Simply stated, Mitchell s hypothesis suggests that electron transfer is accompanied by transport of protons across the membrane. 

According to the chemiosmotic coupling hypothesis, ATP synthesis decreases the proton electrochemical gradient and hence stimulates the respiratory chain to pump more protons across the mitochondrial inner membrane and maintain the gradient. However, electron supply to the respiratory chain also affects respiration and ATP synthesis. For example, calcium stimulates mitochondrial matrix dehydrogenase, and increases the electron supply to the respiratory chain and hence the rate of respiration and ATP synthesis. 

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

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 ... 

Mitchell, P. Keilin s Respiratory Chain Concept and Its Chemiosmotic Consequences. Science 206, 1148-1159 (1979). [A Nobel Prize lecture by the scientist who first proposed the chemiosmotic coupling hypothesis.]... 

The chemical coupling hypothesis failed to explain why mitochondrial membrane must be intact during ATP synthesis. How does the chemiosmotic theory account for this phenomenon ... 

Figure 1. Chemiosmotic coupling in oxidative phosphorylation. The model is drawn according to Mitchell s hypothesis for mitochondria, but might also apply to other systems of phosphorylation.

Much investigative effort has been directed towards the elucidation of the coupling of the two aspects of oxidative phosphorylation. Historically, three mechanisms have been proposed the chemical coupling hypothesis, the chemiosmotic hypothesis and conformational coupling hypothesis. 

Slater, E. C., 1967, An evaluation of the Mitchell hypothesis of chemiosmotic coupling in oxidative and photo synthetic coupling, Eur. J. Biochem. 1 317. 

Peter Mitchell s chemiosmotic hypothesis revolutionized our thinking about the energy coupling that drives ATP synthesis by means of an electrochemical gradient. How much energy is stored in this electrochemical gradient For the transmembrane flow of protons across the inner membrane (from inside [matrix] to outside), we could write... 

In 1961, Peter Mitchell proposed a novel coupling mechanism involving a proton gradient across the inner mitochondrial membrane. In Mitchell s chemiosmotic hypothesis, protons are driven across the membrane from the matrix to the intermembrane... 

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). 

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. 

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. 

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