Proton and hydrogen atom tunnelling in hydrolytic and redox enzyme catalysis

We discuss a broad theoretical frame for hydrogen transfer in chemical and biological systems. Hydrogen tunnelling, coupling between the tunnel modes and the environment, and fluctuational barrier preparation for hydrogen tunnelling are in focus and given precise analytical forms. Specific rate constants are provided for three limits, i.e., the fully diabatic, the partially adiabatic, and the fully adiabatic limits. These limits are all likely to represent real chemical or biological hydrogen transfer systems. The rate constants are referred particularly to the driving force and temperature dependence of the kinetic isotope effect (KIE). The origin of these correlations is different in the three limits. It is rooted in the tunnel factor and weak excitation of the heavier isotopes in the former two limits, giving a maximum for thermoneutral processes. A new observation is that the adiabatic limit also accords with a KIE maximum for thermoneutral processes but the KIE is here reflected solely in the activation Gibbs free energy differences, in this case rooted in the low-frequency environmental nuclear dynamics. Three systems of biological hydrogen tunnelling, viz. lipoxygenase, yeast alcohol dehydrogenase, and bovine serum amine oxygenase, offer unusual new cases for analysis and have been analysed using the theoretical frames. All the systems show large KIEs and strong indications of hydrogen tunnelling. They also represent different degrees of fluctuational barrier preparation, with lipoxygenase as the most rigid and bovine serum amine oxygenase as the softest system.