Can free energy transduction be localized at some crucial part of the enzymatic cycle?

Free energy transfer from one small molecule (ligand, substrate, etc.) to another can in general be comprehended only in terms of complete kinetic cycles, not in terms of an individual transition in the cycle, or of a single 'energized' state in the cycle, or of binding strengths of the small molecules on the enzyme, or of their standard chemical potentials when bound. The reason these latter approaches fail is that the enzyme molecule is as much a specific participant in the step by step proceedings as are the small molecules; small molecule free energies cannot be separated from enzyme contributions or, in general, from each other except at the complete cycle level. It is possible to follow the 'flow' of the total free energy of enzyme + small molecules among various subdivisions or categories, as the system proceeds through the states of the transducing cycle. These categories can be understood in molecular terms but several of them involve the enzyme in a way that is inseparable from the small molecules. Hence this procedure also, does not allow localization within the cycle of the supposed point of transfer of free energy from one small molecule to another.

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