Dynamical contributions to enzyme catalysis: Critical tests of a popular hypothesis

Enzymes accelerate a variety of metabolic reactions and they control signaling, energy transduction, and transcription and translation of generic information. Their ability to catalyze reactions by many orders of magnitude allows cells to carry out reactions that otherwise would not occur on biologically useful time scales. To date, many proposals have been put forward to rationalize the catalytic power of enzymes. However, no convincing evidence for dynamical contributions to enzyme catalysis of ground-state reactions has been obtained yet. Although enzymes have evolved to lower the activation free energies of reactions dramatically, no enzyme has been shown to increase the transmission factor by more than a factor of about two relative to that for the same reaction in water. Furthermore although nuclear tunneling contributes to the reactions catalyzed by some enzymes, no enzyme has been shown to use a particular vibrational mode in a way that specifically enhances tunneling relative to the reaction in solution.