Examining the importance of dynamics, barrier compression and hydrogen tunnelling in enzyme catalysed reactions

Nuclear quantum mechanical tunnelling is important in enzyme-catalysed H-transfer reactions. This viewpoint has arisen after a number of experimental studies have described enzymatic reactions with kinetic isotope effects that are significantly larger than the semiclassical limit. Other experimental evidence for tunnelling, and the potential role of promoting vibrations that transiently compress the reaction barrier, is more indirect, being derived from the interpretation of e.g. mutational analyses of enzyme systems and temperature perturbation studies of reaction rates/kinetic isotope effects. Computational simulations have, in some cases, determined exalted kinetic isotope effects and tunnelling contributions, and identified putative promoting vibrations. In this review, we present the available evidence – both experimental and computational – for environmentally-coupled Htunnelling in several enzyme systems, namely aromatic amine dehydrogenase and members of the Old Yellow Enzyme family. We then consider the relative importance of tunnelling contributions to these reactions. We find that the tunnelling contribution to these reactions confers a rate enhancement of ∼1000-fold. Without tunnelling, a 1000-fold reduction in activity would seriously impair cellular metabolism. We therefore infer that tunnelling is crucial to host organism viability thereby emphasising the general importance of tunnelling in biology.