Chemical coupling hypothesis oxidative

By the mid-1950s, therefore, it had become clear that oxidation in the tricarboxylic acid cycle yielded ATP. The steps had also been identified in the electron transport chain where this apparently took place. Most biochemists expected oxidative phosphorylation would occur analogously to substrate level phosphorylation, a view that was tenaciously and acrimoniously defended. Most hypotheses entailed the formation of some high-energy intermediate X Y which, in the presence of ADP and P( would release X and Y and yield ATP. A formulation of the chemical coupling hypothesis was introduced by Slater in 1953,... 

The spatial separation between the components of the electron transport chain and the site of ATP synthesis was incompatible with simple interpretations of the chemical coupling hypothesis. In 1964, Paul Boyer suggested that conformational changes in components in the electron transport system consequent to electron transfer might be coupled to ATP formation, the conformational coupling hypothesis. No evidence for direct association has been forthcoming but conformational changes in the subunits of the FI particle are now included in the current mechanism for oxidative 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. 

The chemical coupling hypothesis (1953) was modelled on the glycolytic oxidation of glyceralde-hyde 3-phosphate to 3-phosphoglycerate (Section 11.2) but it is generally accepted that this hypothesis is incorrect. 

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). 

Throughout this discussion of oxidative phosphorylation, we have assumed that the coupling mechanisms involve the formation of high-energy intermediates. This chemical hypothesis is not accepted by all the chemiosmotic hypothesis of oxidative phosphorylation was proposed by Mitchell in 1961, and in 1966 Boyer [148] proposed a new hypothesis involving conformation coupling. 

Ortho-para oxidative coupling of the diphenol, reticuline (6.148), can be conceived of as giving the dienone (6.149) which could afibrd thebaine (6.151) as shown [101]. This hypothesis is strongly supported by the observation that this dienone, (6.149), called salutaridine, is a constituent of opium poppies, is formed from radioactive tyrosine (6.94) and norlaudanosoline (6.123), and is a highly efficient and specific precursor for the opium alkaloids. The transformation of salutaridine (6.149) into thebaine (6.151) requires a further ring-closure, which occurs chemically when the two epimeric alcohols (6.150) are treated with acid. In contrast to the purely chemical reaction, only one of the alcohols was efficiently converted into thebaine in vivo, indicating that the reaction is enzyme mediated (and therefore part of normal biosynthesis). 

Mitochondria are known as the "power plants" of aerobic cells, the primary function of which is fatty acid oxidation to CO2 and H2O, and ATP synthesis. As mentioned in the INTRODUCTION, the chemiosmotic hypothesis of Mitchell suggests that coupled electron and ion movements are crucial to redox protein chain energy transduction into ATP movement. The key questions to be answered are (i) how are electrochemical potential gradients (Ap/Ax) of protons across the biomembranes generated, (ii) how are electrons, ions and chemical species transported across the membrane, and (iii) how are such potential gradients (Ap/Ax) used to drive the synthesis of ATP ... 

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