Oxidative phosphorylation is the hypothetical means by which ATP is generated from inorganic phosphate and ADP within mitochondria. It is tightly linked to the passage of high-energy electrons down the electron transfer chain.
The most plausible hypothesis to link the production of ATP by the enzyme ATP synthase with the reactions in the electron transfer chain is that of chemiosmosis:
- electron transfer at certain enzymes within the respiratory chain acts to pump protons from the inside to the outside of the inner mitochondrial membrane
- this establishes a proton gradient across the membrane
- the passage of the protons back across the membrane down the electrochemical gradient causes a conformation change in ATP synthase; the proton gradient and ATP synthase are coupled
- the conformation change in ATP synthase catalyzes the coupling of ADP and inorganic phosphate to form ATP
- ATP is then used as a universal energy intermediate by the cell
Oxidative phosphorylation is dependent on the tricarboxylic acid cycle, and to a lesser extent pathways such as glycolysis, to provide a 'driving force' in terms of NADH and FADH2 for the electron transport chain. Conversely, when supplies of NADH and FADH2 are low, ATP hydrolysis by ATP synthase can be coupled to produce them by the electron transport chain working in reverse. This is facilitated by all of the electron transport chain enzymes being near-equilibrium.
Further, the uncoupling of ATP synthase and the electron transport chain occurs in brown fat. The proton gradient is used to create heat rather than ATP.