Theoretical Approach to the Concept of High Energy

The amount of free energy that might become available when ATP is hydrolyzed can be estimated from the values of the equilibrium constant (Keq) and of the standard free energy of hydrolysis (ΔG°) of ATP. The Keq is determined by dividing the molar concentration of the product by the molar concentration of reactant measured after the hydrolytic reaction of ATP reaches equilibrium. In water, the Keq of ATP hydrolysis may vary from 10⁴ to 10⁶ depending on the pH value of the solution, on the temperature, and on the concentration of divalent cations in the media.

The ΔG° is calculated by multiplying the logarithm of the Keq by —4.5 and by the absolute temperature in which the Keq was measured. Thus, the higher the value of the equilibrium constant for the hydrolysis, more negative the ΔG° of ATP.

The concept of high-energy compounds has been analyzed primarily from a theoretical viewpoint. Until the past two decades, interaction of reactant and product with the solvent were not regarded as playing a role in determining the energy of hydrolysis of phosphate compounds. At that time it was thought that intramolecular effects such as opposing resonance, electrostatic repulsions, and electron distribution along the P-O-P backbone were the dominant factors contributing to the large negative free energies of hydrolysis of ATP.

In these formulations, water was ignored; however, when dissolved in water, the phosphate compounds interact strongly with the solvent. The water molecules that organize around the phosphate compound shield the charges of the molecules, neutralizing the electrostatic repulsion, and form bridges between different atoms of the molecule, reinforcing weak points generated along the molecule backbone by opposing resonances.

Recognition of these effects led to the view that the energy of hydrolysis of a phosphate compound would be determined by the differences in solvation energies of reactants and products. Solvation energy is the amount of energy needed to remove the solvent molecules that organize around the molecule in solution. Thus, a more solvated molecule would be more stable (i.e., less reactive) than a less solvated molecule, and the equilibrium constant for hydrolysis would have a high value because the products of the reaction are more solvated than the reactant.

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