Hydrogens or their electrons, pass down the electron transport chain in a series of redox reaction. The electrons entering the electron transport system have relatively high energy content. As they pass along the chain of electron acceptors, they lose much of their energy, some of which is used to pump the protons across the inner mitochondrial membrane. The flow of electrons in the electron transport is usually coupled tightly to the production of ATP with the help of the enzyme ATP synthetase, and it does not occur unless the phosphorylation of ADP can also proceed. This prevents a waste of energy, because high-energy electrons do not flow unless ATP can be produced. Because the phosphorylation of ADP to form ATP is coupled with the oxidation of electron transport components, this process of making ATP is referred to as oxidative phosphorylation. The electron transport and oxidative phosphorylation depends upon the availability of ADP and Pi and it is referred as acceptor control of respiration.
Peter Mitchell got the Nobel prize in 1978 for his theory of chemiosmosis.
The chemiosmotic theory of Mitchell claims that oxidation of components in respiratory chain generates hydrogen ion and ejected across the inner membrane. The electrochemical potential difference resulting from the asymmetric distribution of the hydrogen ion is used as the driving force (potential energy). This consist of a chemical concentration gradient of protons across the membrane (pH gradient) also provides a charge gradient. The inner mitochondrial membrane is impermeable to the passage of protons, which can flow back into the matrix of the mitochondrion only through special channels in the inner mitochondrial membrane. In these channels, the enzyme ATP synthetase is present. As the protons move down the energy gradient (proton motive force = chemiosmotic energy), the energy releases is used by ATP synthetase to produce ATP.
The chemiosmotic model explains that this electrochemical potential difference across the membrane is used to drive a membrane located ATP synthetase which couple the energy to ADP, to form ATP. Protons are pumped across the inner mitochondrial membrane by three electron transfer complexes, each associated with particular steps in the electron transport system. As electrons are transferred along the acceptors in the electron transport chain, sufficient energy is released at three points to convey protons across the inner mitochondrial membrane and ultimately to synthesize ATP.
ATP synthetase or F0 F1 ATPase, has two major components, F0 and F1 (F for factor).F1 consists of 5 polypeptides, with stoichiometry a3, b3, g, d, e. The F1 component resembles a doorknob protruding into the matrix from the inner membrane. It is attached to Fo by a stalk, which is embedded in the inner membrane and extend across it. F0 is a complex of integral membrane proteins. When F1 is carefully extracted (from inside out vesicles prepared) from the inner mitochondrial membrane, the vesicles still contain intact respiratory chains. However, since it no longer contain the F1 knobs, as confirmed by electron microscopy, they cannot make ATP. When a preparation of isolated F1 is added back to such depleted vesicles under appropriate conditions, to reconstitute the inner membrane structure, with F1 knobs, the capacity of the inner membrane vesicles to carry out energy coupling between electron transport and ATP formation is restored. This shows the precise arrangement of these F0 and F1 make the ATP synthetase to form complexes called respiratory assemblies. It is proposed that an irregularly shaped “shaft” linked to Fo was able to produce conformational changes as follows
1. A loose conformation in which the active site can loosely bind ADP + Pi
2. A tight conformation in which substrates are tightly bound and ATP is formed
3. An open conformation that favours ATP release.
As the protons move down the energy gradient, the energy releases is used by ATP synthetase to produce ATP.