Chemical coupling hypothesis

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. 

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 ... 

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. 

The chemical coupling of catharanthine and vindoline to yield anhydrovinblastine led to the obvious hypothesis that this compound might also be the first product of dimerization in the plant, and the dimeric precursor of vinblastine and vincristine. For three years it was not possible to find anhydrovinblastine in the plant, until Scott et al. in 1978 [115], by modifying the established methods for extraction and purification of alkaloids, isolated anhydrovinblastine from C. roseus plants, with incorporation of radiolabelled catharanthine and vindoline, thus proving that anhydrovinblastine was actually a natural product. 

While the chemiosmotic hypothesis does not embrace the need for the mediation of a chemical coupling compound(s) or for conformational coupling interaction(s) between the redox system and the ATP-synthesizing system, Mitchell notes that there is every reason to believe that conformational interactions may be involved within the translocation system itself, in a manner consistent with the role of conformational changes in enzymic catalysis, as elaborated in Chapters 3 and 4 of this book. 

Based on these preliminary findings, related couplings to pyruvates and iminoacetates were explored as a means of accessing a-hydroxy acids and a-amino acids, respectively. It was found that hydrogenation of 1,3-enynes in the presence of pyruvates using chirally modified cationic rhodium catalysts delivers optically enriched a-hydroxy esters [102]. However, chemical yields were found to improve upon aging of the solvent 1,2-dichloroethane (DCE), which led to the hypothesis that adventitious HC1 may promote re-... 

It is our hypothesis that the presence of large amounts of K" " in the cell is a major determining factor in ozone injury at the cellular level. The alteration of K+ permeability (coupled with an inhibition of the mechanism for regaining the lost K" ") causes a large loss of K" " (down an electro-chemical potential gradient) followed by a rapid loss of osmotic water. 

Further demonstrations of this sort of counterflow phenomenon for many different substrates in virtually every type of cell have been used as functional hallmarks of carrier-mediated transport. Experimental demonstration of this effect precludes transport being mediated either by simple diffusion or by fixed pores in the membrane. In reviewing 20 years of experimental work related to the carrier hypothesis, LeFevre (1975) lists a number of key functional properties of carrier mediated transport, all of which have stood the test of the subsequent 20 years. These include saturation of transport with increased substrate concentration and associated phenomena such as competition between similar substrates, high rates of unidirectional transport, and countertransport. Also covered are flux coupling (including trans effects and cotransport), chemical specificity, inhibition by protein-specific reagents, hormonal regulation, and a steep dependence of the rate of transport on temperature (included only to bemoan its common inclusion in textbooks ). 

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