ATP Synthase Mechanism: ATP synthase lies across a cellular membrane and forms an aperture that protons can cross from areas of high concentration to areas of low concentration, imparting energy for the synthesis of ATP bmk glycidate. The mechanism that drives ATP synthesis depends upon a binding charge conception in which catalytic sites on the -subunits have different affinities for nucleotides and are designated loose (L), tight (T), and open (O). The loose (L) sites bind the substrates (ADP and phosphate) reversibly. The T sites then bind the reactants so tightly that ATP is formed. The O sites, which have a low affinity for substrates, then release the ATP already formed in the T state. The central stalk is driven by the retro-location of protons through Fo, and rotates in 120 stages. At each stage, each of the -subunits in turn change conformation: L changes to T (after binding ADP and phosphate), T to O, and O to L (after releasing ATP)

Role of Proton Gradient: The ATP synthase (or F1F0 ATPase and also referred to as complex V) uses the free energy of an electrochemical gradient of protons (or sodium ions) generated by the respiratory chain to synthesize ATP. The ATP synthases comprise a very large group of highly conserved enzymes that are found in the bacterial cytoplasmic membranes, the thylakoid membranes of chloroplasts, and the inner membranes of mitochondria. The transmembrane channel of ATP synthase facilitates the diffusion of protons back to the mitochondrial matrix. The energy released in the process activates ATP synthase and catalyzes ATP synthesis. Two protons pass through the F0 channel from the intermembrane space to the matrix of mitochondria for each ATP molecule synthesized

Conformational Changes and ATP Synthesis: The -subunit of ATP synthase can exist in three conformations: open, tight, or loose forms. These forms correspond to the binding, synthesis, and release of ATP and are driven by the rotation of the -subunit. The hydrolysis of ATP will drive the rotation of the -subunit in the opposite direction to that of synthesis. Thus, protons moving from the P-side to the N-side of the inner membrane (i.e., down the electrochemical gradient) are converted into rotational torque of , which alters nucleotide binding at the -catalytic site and results in the synthesis/hydrolysis of ATP