Bi2-Coenzymes in Enzymatic Radical Reactions

The homolytic cleavage of the Co - C bond of the protein-boimd organo-metallic cofactor AdoCbl (2) is the initial step of the coenzyme Bi2-catalyzed enzymatic reactions. Halpern quoted that adenosyl cobamides can be considered as reversibly functioning sources for organic radicals [119]. A neutral aqueous solution of 2 is remarkably stable with a half-Ufe of 10 s (in the dark at room temperature), but decomposes, mainly with the homolysis of the Co-C bond, at higher temperatures [119,123]. The coenzyme B12-catalyzed enzyme reactions occur with maximal rates of approximately 100 s [173,239]. Rapid formation of Co(ll)corrins occurs only with addition of substrate to a solution of holoenzyme (or of apoenzymes and 2), as demonstrated in most of the known coenzyme Bi2-dependent enzymes, e.g., in methyl-malonyl-CoA mutase [121], glutamate mutase [202] and ribonucleotide reductase [239]. 

an intriguing feature of the coenzyme Bi2-dependent enzymes is the dramatic ( lO -fold) labihzation of the bound organometallic cofactor towards homolysis of the Co-C bond [119,123,173]. The mechanism of the enzyme (and substrate-induced) labihzation of this Co-C bond is stiU a key problem, and much discussed, in Bn-chemistry. Evidence for covalent restructuring of the bound cofactor (except for the formation of the base-off/His-on form in the carbon skeleton mutases) is not available [75,119,123, 173,194]. In addition protein and solvent molecules can only weakly stabihze a radical center [240]. Steric distortions of the protein-bound cofactor were discussed as means for the enhanced rate of Co - C bond homolysis [51,119, 163,217]. Halpem s theory of an upwards conformational distortion of the 

The rearrangement steps of B -dependent enzymatic rearrangements are now assumed to be accomphshed by tightly protein-bound radicals that are controlled in their reaction space [178,184,199] but (practically) unassisted by the Co(II)-corrin fragment of the coenzyme (which has a spectator role) [184,199]. In the coenzyme B -dependent enzymes, the main role of the bound cofactor thus is only the production and controlled presentation of the 5 -deoxy-5 -adenosyl radical from homolysis of the Co - C bond of AdoCbl (2), with little structural reorganization occurring in the cobalt-corrin part. 

---