Free energy differences between enzyme bound states.

A theory is presented that describes the free energy difference between the enzyme-substrate (ES) and enzyme-product (EP) complexes that is expected in enzymes optimized for catalytic efficiency. In such enzymes, the free energy drop between ES and EP complexes reflects a portion of the chemical potential difference between substrates and products outside the active site under physiological conditions. Qualitative and quantitative predictions of the model are discussed and compared with experimental data. The controversy over the kinetically optimal free energy profile for an enzymatic reaction operating under constraints set forward by Albery & Knowles (1976) is resolved.