Kinetic Isotope Effects as Probes for Hydrogen Tunneling, Coupled Motion and Dynamics Contributions to Enzyme Catalysis

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Abstract
Since the early days of enzymology attempts have been made to deconvolute the various contributions of physical phenomena to enzyme catalysis. Here we present experimental and theoretical studies that examine the possible role of hydrogen tunneling, coupled motion, and enzyme dynamics in catalysis. In this review, we first introduce basic concepts of enzyme catalysis from a physical chemistry point of view. Then, we present several recent developments in the application of experimental tools that can probe tunneling, coupled motion, dynamic effects and other possible physical phenomena that may contribute to catalysis. These tools include kinetic isotope effects (KIEs), their temperature dependency and H/D/T mutual relations (the Swain­Schaad relationship). Several theories and models that assist in understanding those phenomena are also described. The possibility that these models invoke a direct role for the enzyme's dynamics (environmental fluctuations and rearrangements) is discussed. Finally, the need to compare the enzymatic reaction to the uncatalyzed one while investigating contributions to catalysis is emphasised.