Suicide Inactivation in Adenosylcobalamin-Dependent Enzymes

Abstract

Because organic radicals are highly reactive species, they are traditionally considered to be detrimental to biological systems. Yet intriguingly, adenosylcobalamin (AdoCbl) dependent enzymes exploit the high reactivity of such radicals to facilitate an otherwise difficult rearrangement of adjacent groups.[1,2] A vital component of these reactions is the requirement of 5′-deoxyadenosyl radical (Ado•), derived from the homolytic cleavage of the cobalt–carbon bond of AdoCbl, to mediate two distinct hydrogen atom transfers (Scheme 1). Clearly, the ability of AdoCbl-dependent enzymes to control the specificity of any radical must be met with rigour so as to minimize aberrant side-reactions, a concept often referred to as negative catalysis.[3] However, an emerging theme for these enzymes is the possibility for their irreversible inactivation, resulting from their dependence on radicals for catalysis. One manifestation of this so-called suicide inactivation is unmistakably revealed through the use of suitably chosen AdoCbl and substrate analogues. Analyses of the inactivation products can provide valuable information on