Classical Theories of Oxidative Phosphorylation | Respiration

The following points highlight the top three classical theories of oxidative phosphorylation. The theories are: 1. The Chemical Coupling Theory 2. The Conformational Coupling Theory and 3. The Chemiosmotic Coupling Theory.

Classical Theory # 1. The Chemical Coupling Theory:

This theory was first proposed by Slater in 1953 and is based on the principles of sub­strate-level phosphorylation as illustrated by reaction sequence for glyceraldehyde-3-phosphate dehydrogenase in glycolysis resulting in the formation of one ATP molecule and 3-phosphoglyceric acid, (For details see glycolysis).

According to this theory (Fig. 16.13) a reduced electron carrier of the respiratory chain (e.g., AH₂) reacts with an oxidised carrier (e.g., B) which is adjacent to it with sufficient free energy drop occurring to allow the reaction of A with an unknown compound C to give a non phosphorylated high energy intermediate compound A~C. B is reduced to BH₂.

In the next sequential exchange reactions, C is transferred to phosphate to form a phosphorylated intermediate C~P. The electron carrier A becomes free and oxidised.

Finally, phosphate from C~P is transferred to ADP to give ATP. The unknown compound C becomes free and recycled.

Alternatively, there may be a parallel scheme of reaction in which the high-energy non- phosphorylated intermediate is formed with BH₂ instead A (Fig. 16.13).

The chemical coupling theory did not find much support because no phosphorylated in­termediates or high-energy intermediates of the respiratory carriers have yet been identified unequivocally.

Classical Theory # 2. The Conformational Coupling Theory:

This theory was first put forward by Boyer in 1964 and according to this the free energy liberated during electron transport is conserved as a conformational change in the protein component of a respiratory electron carrier or complex of carriers and this change is associated in some way with the phosphorylation of ADP to form ATP.

Boyer suggested that conformational change in an electron carrier probably brought a carboxyl and sulphydryl group very close to each other to form an acyl-s-linkage (Fig. 16.14 A) and that this was the ‘high-energy intermediate’ which could drive ATP synthesis.

Based on conformational coupling theory Green and Ji (1972) have given their electro-mechanochemical coupling theory which envisaged conformational changes in enzyme complexes rather than in individual carriers.

According to their model the transport of elec­trons brings about a conformational change in one of the electron transport complexes in the form of mechanical and electrical strain components. Similar mechanical and electrical changes are in turn induced in an ATPase Complex. The reverse conformational change now leads to the synthesis of ATP bringing back the electron transport complex and the ATPase complex in their original form (Fig. 16.14 B). Although, conformational coupling theory is quite attractive but main difficulty with this theory is the problem of setting up experiments to test it.

Classical Theory # 3. The Chemiosmotic Coupling Theory:

This theory was first put forward by Nobel laureate Peter Mitchell in 1961 and is most convincing of all the three theories to explain the mechanism of mitochondrial oxidative phos­phorylation. It is also equally applicable to chloroplastic photophosphorylation.

The main feature of this theory (Fig. 16.15) is a membrane located reversible ATPase. The membrane is mitochondrial in case of oxidative phosphorylation and chloroplastic in case of photophosphorylation.

The ATPase reversibly catalyses the following reaction:

This reaction is assumed to be anisotropic so that the active centre is accessible to H⁺ but not OH^– from the outer side of the membrane. On the other hand it is accessible only to OH^– but not H⁺ from the inner side of the membrane. The active centre is assumed to be relatively inaccessible to water and the membrane almost impermeable to ions.

It is quite obvious from the ATPase catalysed reversible reaction that the removal of H⁺ and OH^– would favour the reaction towards ATP synthesis.

According to Mitchell H⁺ and OH^– can be removed by membrane bound electron transport chain and the operation of ATPase in the following way:

a. The oxidation of the reduced electron carrier e.g., AH₂ to A with the simultaneous reduction of O to H₂O leads to the accumulation of H⁺ on the inner side and OH^– on the outer side of the membrane.

b. These accumulations of H⁺ on the inner side of the membrane pull OH^– from the ATPase catalysed reaction. Similarly, accumulation of OH^– on the outer side of the membrane pulls H⁺ from the ATPase catalysed reaction. Thus, the equilibrium is shifted in favour of ATP synthesis (Fig. 16.15). The dehydrating force which drives the ATPase catalysed reaction in the direction of ATP synthesis is derived from the chemical potential differential of the OH^– and H⁺ across the membrane.

Mitchell’s hypothesis also predicted the existence of membrane transporters or specific exchange diffusion carriers which has been shown to be correct. These carriers permit revers­ible exchange of anions (e.g. CI^–) for OH^– and cations (e.g., K⁺) for H⁺ and regulate the pH and osmotic differential across the membrane. These systems permit the movements of essen­tial metabolites without breaking the membrane potential which is essential for ATPase catalysed reaction in the direction of ATP synthesis.