Vitamin B12, in the form of its coenzyme, is a cofactor in a series of eleven enzyme-catalyzed transformations. Of these, three enzymes: Beta-methylaspartate mutase, methylmalonyl-SCoA mutase and methylitaconate mutase are of special interest because they catalyze carbon-skeleton rearrangements for which there have been no analogues in organic chemistry. In addition, there are four amino mutases in this series which also lack good precedent. In this proposal, chemical nonenzymic model reactions will be explored with the aim of unravelling the mechanism of action of vitamin B12. New models designed to explore the hydrogen abstraction, and new models for the amino mutase and Beta-methylaspartate mutase rearrangements will be examined. Carbon-13 labelling studies of the methylitaconate mutase rearrangement will be carried out. Special effort will be devoted to the further development of mass spectrometry as an analytical tool in the alkyl cobalamin series. The possible intermediacy of free radical intermediates will be explored using models. Stereochemical studies of the methylitaconate mutase catalyzed rearrangement will be conducted.
| Choi, G Y; Choi, S C; Galan, A et al. (1990) Vitamin B12S-promoted model rearrangement of methylmalonate to succinate is not a free radical reaction. Proc Natl Acad Sci U S A 87:3174-6 |
