Phosphorylation energy hypothesis

Synergistic action of kinases and phosphatases and the phosphorylation energy hypothesis... 

H. Qian. Phosphorylation energy hypothesis open chemical systems and their biological functions. Annu. Rev. Phys. Chem., 58 113-142, 2007. 

Qian H. 2007. Phosphorylation energy hypothesis Open chemical systems and then biological functions. Annual Review of Physical Chemistry 58 113. 

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,... 

In this hypothesis, Apjj+. is still an indispensable component of the energy transduction since it is required for the initiation and continuation of phosphorylation. 

The hypothesis of chemiosmotic mechanism of the oxidative phosphorylation the concentration gradient of H+ ions, formed by the electron transfer energy, is required for speeding up ATP synthesis from ADP and phosphate according to the mechanism based on quick withdrawal of formed H20 molecules dissociated to H+ and OH ions. 

Oxidative phosphorylation is ATP synthesis linked to the oxidation of NADH and FADH2 by electron transport through the respiratory chain. This occurs via a mechanism originally proposed as the chemiosmotic hypothesis. Energy liberated by electron transport is used to pump H+ ions out of the mitochondrion to create an electrochemical proton (H+) gradient. The protons flow back into the mitochondrion through the ATP synthase located in the inner mitochondrial membrane, and this drives ATP synthesis. Approximately three ATP molecules are synthesized per NADH oxidized and approximately two ATPs are synthesized per FADH2 oxidized. 

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). 

Early proposals concerning the mechanism of the energy-linked transhydrogenase reaction were based on the chemical hypothesis of oxidative phosphorylation [82] and visualized the involvement of high-energy intermediates of the type 1 X, NADH I, NADP I, etc. [29,46]. These proposals, however, just as the chemical hypothesis as a whole, had to be abandoned because of lack of experimental evidence. 

Mitchell s highly innovative hypothesis that oxidation and phosphorylation are coupled by a proton gradient is now supported by a wealth of evidence. Indeed, electron transport does generate a proton gradient across the inner mitochondrial membrane. The pH outside is 1.4 units lower than inside, and the membrane potential is 0.14 V, the outside being positive. As calculated on page 508, this membrane potential corresponds to a free energy of 21.8 kj (5.2 kcal) per mole of protons. 

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