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First author of Reconstitution of Purple Membrane Vesicles Catalyzing Light-driven Proton Uptake and Adenosine Triphosphate Formation by Efraim Racker and others.

Animal cells conserve part of the free energy from nutrient oxidation in ATP and electrochemical gradients, then couple their consumption to synthesis, transport and movement. The relevant quantity is the actual Gibbs free energy change,where $Q$ is the appropriate reaction quotient, $R$ the molar gas constant and $T$ the absolute temperature. A reaction with a positive free-energy change can proceed when physically coupled to one whose negative change makes the combined process favourable. Merely placing an exergonic reaction nearby does not accomplish coupling: an enzyme, shared intermediate or molecular machine must link the processes.

Oxidation of carbohydrates and fats supplies NADH and other reducing equivalents. In the mitochondrial electron transport chain, transfer towards oxygen releases free energy. Complexes I, III and IV couple electron transfer to proton translocation from the matrix to the intermembrane space; complex II transfers electrons without directly pumping protons. The inner mitochondrial membrane retains the resulting proton-motive force. For movement of one mole of protons from outside to inside, defineHere $F$ is the Faraday constant and $\psi$ is the electrical potential. Both the relatively negative matrix potential and its relatively alkaline pH favour inward movement. An inward driving voltage of magnitude $0.18\mathrm{V}$ corresponds to approximately $17.4\mathrm{kJ}\mathrm{mo}{\mathrm{l}}^{-1}$ per mole of protons. This is an illustrative calculation, not a universal mitochondrial measurement.

Proton movement through ATP synthase drives rotation and conformational changes that couple ADP and phosphate to ATP formation. Several protons are required per ATP, and transport of phosphate and adenine nucleotides adds energetic costs; there is no universal whole-number ATP yield for every animal cell. Reconstitution of a light-driven proton pump with ATP-synthesizing machinery in lipid vesicles showed that an independently generated gradient can support ATP formation. This experiment used an artificial mixture of components, providing a mechanistic test rather than a model of animal-cell photosynthesis.^[ref] In mitochondria, respiratory inhibitors, an ATP-synthase inhibitor and a protonophore give distinct predictions for oxygen consumption, ATP production and the gradient, helping distinguish electron transfer from coupling.

ATP then supplies a mobile chemical coupling intermediate. Transfer of a phosphate group can make an otherwise unfavourable biosynthetic step favourable through a common intermediate. sodium-potassium ATPase couples ATP hydrolysis to ion pumping; sodium-dependent cotransport uses the stored gradient for secondary active transport. Myosin couples its ATPase cycle to force and displacement on actin. Substrate-level phosphorylation also generates ATP directly during glycolysis and other reactions without an obligatory respiratory gradient. ATP hydrolysis is favourable because of the free-energy difference between the full reactant and product states under cellular conditions, not because breaking a bond alone releases energy.

Conversion is never perfectly efficient: heat is produced, proton leak can bypass ATP synthase, and controlled uncoupling can favour heat production. ATP concentration and the ATP/ADP/phosphate ratio reflect a maintained nonequilibrium state. Energy transduction is therefore a chain of coupled chemical, electrical, osmotic and mechanical changes, sustained by metabolism and constrained by thermodynamics.