Acid–Base Catalysis by Enzymes

Abstract

Abstract Proton transfer is the commonest reaction that enzymes perform. Most enzyme reactions go by ionic mechanisms, involving the creation or disappearance of charge. Such reactions are typically acid or base catalysed, but acid and base concentrations are minimal under physiological conditions near pH 7. Enzymes have evolved subtle and highly effective solutions to this problem, involving general acid and general base catalysis by the functional groups available on the side‐chains of amino acids strategically placed in their active sites. General acid and general base catalysis by the same functional groups can be observed, and the relevant mechanisms elucidated, by studying simple systems. But this work typically involves the use of properly designed activated substrates. The extraordinary efficiency of such catalysis in enzyme active sites has not so far been reproduced in model systems, and this remains an active area of investigation. Key Concepts: The enzyme active site provides a highly sophisticated reaction vessel, tailored to the needs of the specific reaction and the specific substrate. General acid and general base catalysis are first‐line support services for the making and breaking of covalent bonds that define the chemistry of metabolic processes. The unexceptional functional groups available on the side‐chains of amino acids acquire exceptional catalytic proficiency when strategically placed in enzyme active sites.