The transfer of hydride, proton, or H atom between substrate and cofactor in enzymes has been extensively studied for many systems, both experimentally and computationally. A simple equation for the reaction rate, an analog of an equation obtained earlier for electron transfer rates, is obtained, but now containing an approximate analytic expression for the bond rupture-bond forming feature of these H transfers. A "symmetrization," of the potential energy surfaces is again introduced ͓R. A.

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... us, J. Chem. Phys. 43, 679 ͑1965͒; J. Phys. Chem. 72, 891 ͑1968͔͒, together with Gaussian fluctuations of the remaining coordinates of the enzyme and solution needed for reaching the transition state. Combining the two expressions for the changes in the difference of the two bond lengths of the substrate-cofactor subsystem and in the fluctuation coordinates of the protein leading to the transition state, an expression is obtained for the free energy barrier. To this end a two-dimensional reaction space ͑m , n͒ is used that contains the relative coordinates of the H in the reactants, the heavy atoms to which it is bonded, and the protein/solution reorganization coordinate, all leading to the transition state. The resulting expression may serve to characterize in terms of specific parameters ͑two "reorganization" terms, thermodynamics, and work terms͒, experimental and computational data for different enzymes, and different cofactor-substrate systems. A related characterization was used for electron transfers. To isolate these factors from nuclear tunneling, when the H-tunneling effect is large, use of deuterium and tritium transfers is of course helpful, although tunneling has frequently and understandably dominated the discussions. A functional form is suggested for the dependence of the deuterium kinetic isotope effect ͑KIE͒ on ⌬G°and a different form for the 13 C KIE. Pressure effects on deuterium and 13 C KIEs are also discussed. Although formulated for a one-step transfer of a light particle in an enzyme, the results would also apply to single-step transfers of other atoms and groups in enzymes and in solution.