Vitamin B12 is a complex organometallic cofactor associated with three subfamilies of enzymes: the adenosylcobalamin-dependent isomerases, the methylcobalamin-dependent methyltransferases, and the dehalogenases. Different chemical aspects of the cofactor are exploited during catalysis by the isomerases and the methyltransferases. Thus, the cobalt-carbon bond ruptures homolytically in the isomerases, whereas it is cleaved heterolytically in the methyltransferases. The reaction mechanism of the dehalogenases, the most recently discovered class of B12 enzymes, is poorly understood. Over the past decade our understanding of the reaction mechanisms of B12 enzymes has been greatly enhanced by the availability of large amounts of enzyme that have afforded detailed structure-function studies, and these recent advances are the subject of this review.

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The many faces of vitamin B12: catalysis by cobalamin-dependent enzymes.

Chemistry and enzymology of vitamin B12.

How coenzyme B12 radicals are generated: the crystal structure of methylmalonyl-coenzyme A mutase at 2 A resolution.

Coenzyme B12 serves as a cofactor in various enzymatic reactions in which a hydrogen atom is interchanged with a substituent on an adjacent carbon atom. Measurement of the dissociation energy of the coenzyme's cobalt-carbon bond and studies of the rearrangement of model free radicals related to those derived from methylmalonyl-coenzyme A suggest that these enzymatic reactions occur through homolytic dissociation of the coenzyme's cobalt-carbon bond, abstraction of a hydrogen atom from the substrate by the coenzyme-derived 5'-deoxyadenosyl radical, and rearrangement of the resulting substrate radical. The only role thus far identified for coenzyme B12 in these reactions--namely, that of a free radical precursor--reflects the weakness, and facile dissociation, of the cobalt-carbon bond.

http://science.sciencemag.org/content/sci/227/4689/869.full.pdf

Mechanisms of coenzyme B12-dependent rearrangements.

Catalytic chain transfer in free-radical polymerizations.

Thermolysis of the cobalt-carbon bond of adenosylcobalamin. 2. Products, kinetics, and cobalt-carbon bond dissociation energy in aqueous solution

Thermolysis of the cobalt-carbon bond in adenosylcorrins. 3. Quantification of the axial base effect in adenosylcobalamin by the synthesis and thermolysis of axial base-free adenosylcobinamide. Insights into the energetics of enzyme-assisted cobalt-carbon bond homolysis

Benjamin P. Hay

Papers

Thermolysis of the cobalt-carbon bond of adenosylcobalamin. 2. Products, kinetics, and cobalt-carbon bond dissociation energy in aqueous solution

Thermolysis of the cobalt-carbon bond in adenosylcorrins. 3. Quantification of the axial base effect in adenosylcobalamin by the synthesis and thermolysis of axial base-free adenosylcobinamide. Insights into the energetics of enzyme-assisted cobalt-carbon bond homolysis

Thermolysis of adenosylcobalamin: a product, kinetic, and cobalt-carbon (C5') bond dissociation energy study

Thermolysis of the CoC bond in adenosylcobalamin (coenzyme B12)—IV. Products, kinetics and CoC bond dissociation energy studies in ethylene glycol

Cage effects in organotransition metal chemistry: their importance in the kinetic estimation of bond dissociation energies in solution