Oxidative phosphorylation Animation - Formation of ATP & sites of ATP synthesis : Dr G Bhanu Prakash

Respiratory control ensures a tight coupling between electron flow and ATP synthesis, meaning oxygen consumption depends on ADP availability. High ADP (low ATP) increases electron flow and oxygen consumption, crucial during exercise. The binding change mechanism, proposed by Paul Boyer, explains ATP production in the beta subunit of F1. Re-entry of protons through F0 rotates the gamma subunit, which in turn causes conformational changes in the beta subunits of F1, leading to ATP synthesis.

Oxidative phosphorylation involves ATP formation coupled with the oxidation of reducing equivalents. Energy produced during electron transfer through the electron transport chain (ETC) drives ATP synthesis by the enzyme F0F1 ATPase. There are three main ATP-synthesizing sites in the ETC: Complex I (between NAD and coenzyme Q), Complex III (between coenzyme Q and cytochrome C), and Complex IV (between cytochrome C and oxygen). Complex II does not produce ATP.

Each NADH molecule entering the respiratory chain produces 2.5 ATP molecules, while each FADH2 molecule yields 1.5 ATP molecules. This is because Complex I and Complex III pump four hydrogen ions, leading to one ATP each, while Complex IV pumps only two hydrogen ions, producing half an ATP. This updates previous assumptions where NADH produced 3 ATPs and FADH2 produced 2 ATPs.

The most widely accepted explanation for oxidative phosphorylation is Peter Mitchell's Chemiosmotic Theory (1961). This theory states that oxidation and phosphorylation are coupled by a proton gradient across the mitochondrial membrane. This proton motive force, caused by an electrochemical potential difference, drives ATP synthesis.

ATP synthase, also known as Complex V or the smallest molecular motor in the human body, is embedded in the inner mitochondrial membrane. It consists of two sub-complexes: the F0 sub-complex and the F1 sub-complex. The F0 sub-complex is hydrophobic, spans the inner membrane, forms a proton channel, and is made of 10 C protein subunits. The F1 sub-complex is hydrophilic, projects into the mitochondrial matrix, and is composed of nine subunits (3 alpha, 3 beta, 1 gamma, 1 delta, 1 epsilon). The gamma subunit has a bent-axle shape and is surrounded by the alpha and beta subunits.

The flow of protons through F0 causes its rotation, along with the gamma subunit of F1. This rotation leads to ATP production within the beta subunit of the F1 complex, which is the catalytic subunit. ATP synthase functions as a rotor-stator molecular motor, where F0 and the gamma subunit are rotating, while the alpha and beta subunits (excluding gamma) of F1 are stationary.