Steric Course and Mechanism of Coenzyme B12-Dependent Rearrangements
Vitamin B12 is not only one of the most fascinating naturally occurring molecules, its coenzyme form is also a unique co-catalyst. It is unique both in its structure and in its function. By X-ray diffraction studies of Lehnert and Hodgkin a covalent bond has been identified between the central cobalt atom and its axial ligand, 5′-deoxyadenosine. The stability of this metalorganic bond in aqueous solution is surprising and so is its role in a number of enzymic rearrangements. The first of these, the glutamate mutase reaction was discovered 1958 by H.A. Barker et al.1 (Eqn.1). It was and still is a mechanistically intriguing process without chemical precedence. One of the puzzles for chemists is the specific attack and subsequent substitution at a non-activated methyl group, even though hydrogen atoms in more activated positions are available in the molecule. A similar rearrangement, discovered at about the same time both in bacteria and in mammals2,3, turned out to be also dependent on coenzyme B12 (Eqn.2). In the last few years we focused our attention on this rearrangement catalyzed by the enzyme methylmalonyl-CoA mutase and a considerable portion of my lecture will deal with it. Other coenzyme B12-dependent reactions in which a rearrangement is not immediately obvious are catalyzed by dioldehydratases (Eqn.3) and ammonia lyases (Eqn.4).
KeywordsElectron Spin Resonance Electron Spin Reso Minimal Mechanism Coenzyme Form Unlabelled Molecule
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