Dynamic, Electrostatic Model for the Generation and Control of High-Energy Radical Intermediates by a Coenzyme B12-Dependent Enzyme

Abstract

High-energy radical species are widespread in biology as transient reaction intermediates and free radicals. The control of these extremely reactive molecules is crucial to limit oxidative stress and promote healthy physiological function.[1] In some cases this reactivity can be harnessed by a system to do useful work.[2] Over two decades ago Retey discussed how energy can be “borrowed” from an enzyme to effect an unlikely chemical change.[3] In the case of coenzyme B12-dependent enzymes,[4] this energy is “lent” in the form of radical intermediates, which are formed upon substrate binding by Co–C bond homolysis in the cofactor. The energy is then returned by radical pair recombination after turnover (Scheme 1).