Bi2-dependent rearrangements

It is remarkable that, notwithstanding the widespread recognition of the probable role of Co-C bond homolysis in coenzyme Bi2-dependent rearrangements, virtually no information has been available concerning the Co-C bond dissociation energy in coenzyme B12 or closely related compounds. 

Halpern, J., 1985, Mechanisms of coenzyme Bi2-dependent rearrangements. Science 227 8699875. 

Cobalamin-catalyzed reactions are generally classified into two groups methylcob-alamin-dependent reactions (Table 1, entry 1 to 3) and coenzyme Bi2-dependent rearrangements (Table 1, entry 4 to 11). The first group includes the biosynthesis of methionine from homocysteine, the reduction of CO2 to acetic acid via an acetyl-CoA pathway, and the biosynthesis of CH4 also via an acetyl-CoA pathway. ... 

D. M. Smith, S. D. Wetmore, and L. Radom, Theoretical Studies of Coenzyme-Bi2-Dependent Carbon-Skeleton Rearrangements, in Theoretical Biochemistry—Processes and Properties of Biological Systems, L. A. Ericksson, Ed., Elsevier, Amsterdam, The Netherlands, 2001, pp. 183-214. Electronic structure calculations are applied to the understanding and prediction of how enzymes can lower the barriers to the 1,2-shifts in radicals that occur in reactions catalyzed by B12. 

Bothe, H., Darley, D. J., Albracht, S. P., Gerfen, G. J., Golding, B. T., and Buckel, W., 1998, Identification of the 4-glutamyl radical as an intermediate in the carbon skeleton rearrangement catalyzed by coenzyme Bi2-dependent glutamate mutase from Clostridium cochlearium. Biochemistry 37 4105n4113. 

Theoretical Studies of Coenzyme Bi2-Dependent Carbon-Skeleton Rearrangements... 

Banerjee, R. (2003) Radical carbon skeleton rearrangements catalysis by coenzyme Bi2-dependent mutases, Chem. Rev. 103, 2083-94. 

First hydrogen abstraction-rearrangment modle for the coenyme Bi2-dependent mefhylmalonyl-CoA to succinyl-CoA carbon skeleton rearranment reaction, J. Am. Chem. Soc. 114, 7949-7951. 

Like glutamate, 2-methyleneglutarate can be fermented in Clostridia, albeit by a different pathway,and the reaction of MGM is the first step. Less information about MGM is available than other coenzyme Bi2-dependent enzymes. The stereochemistry, purification, and molecular characterization are available. A substrate-based free radical has been observed by EPR spectroscopy. The reaction mechanism is not known, although it likely follows the generic pathway of hydrogen abstraction by the 5 -deoxyadenosyl radical to form a substrate-derived radical, which rearranges to a product-related radical that is quenched by hydrogen transfer from 5 -deoxyadenosine. The mechanism of radical isomerization remains to be proven. ... 

One form of methionine synthase common in bacteria uses lV -methyltetrahydrofolate as a methyl donor. Another form of the enzyme present in some bacteria and mammals uses A/ -methyltetrahydro-folate, but the methyl group is first transferred to cobalamin, derived from coenzyme B12, to form methylcobalamin as the methyl donor in methionine formation. This reaction and the rearrangement of L-methyl-malonyl-CoA to succinyl-CoA (see Box 17-2, Fig. la) are the only known coenzyme Bi2-dependent reactions in mammals. In cases of vitamin B12 deficiency, some symptoms can be alleviated by administering not only vitamin B12 but folate. As noted above, the methyl group of methylcobalamin is derived from W -methyltetrahy-drofolate. Because the reaction converting the methylene form to the 7V -methyl form of tetrahydrofo-... 

Heptamethylcob3rrinate cobester (13) and peripherically functionalized derivatives of 13 were used as catalysts to mimic the rearrangement catalyzed by the coenzyme Bi2-dependent enzyme methylmalonyl-CoA mutase (see Fig. 13) (45). In these studies, the reductive transformation of bromomethyl-malonates to succinates, catalyzed by 13, and similar rearrangement reactions were observed (45). 

FIGURE 16 (Top) A family of rearrangement reactions that depend upon free radical formation involving an enzyme-bound form of the vitamin B12 coenzyme S -deoxyadenosylcobalamin (Fig. 7). The rearrangement of (R) methylmalonyl-CoA to succinyl-CoA (the opposite of the reaction shown here) is one of the two essential vitamin Bi2-dependent reactions in the human body, and plays an important role in fatty acid oxidation, as is indicated in Fig. 12. 

The number of vitamin B 12-dependent reactions is not large. Most of these involve rearrangements of the carbon skeletons of metabolites. Such reactions are important in linking some aspects of fatty acid metabolism to the citric acid cycle. In another form, a vitamin Bi2-derived coenzyme is involved, along with folic acid coenzymes, in the metabolism of one-carbon fragments, including the biosynthesis of methionine. 

The principal role of coenzyme Bj2 in the rearrangement process appears to be as a free radical precursor, a role that depends on the weakness of the cobalt-carbon bond of coenzyme Bi2 . 

Fig. 7.35 SET dynamics of nonadiabatic rearrangement of hydrogen molecule embedded Bi2 cluster, (a) The time dependent mean potential (Hej) and its relation to the adiabatic potential energies of the ground state (GND dashed black line) and excited states (EXl-9 red solid lines). The total energy (Hg ) +Tnuc >s also shown as an almost horizontal line, (b) Time dependent population of 6 adiabatic states the ground (GND), first (EXl), second (EX2), third (EX3), fourth (EX4) and fifth (EX5) excited states, (c) Space-time history of the atoms in three-dimensional Cartesian coordinates (in Bohr units). The trajectories of 12 boron and 2 hydrogen atoms are expressed with green and blue points, respectively, the initial positions of which are marked with red circles embedded in the inner region. The hydrogen atoms are immediately pulled apart and each moves to the surface of the cluster. (Reprinted with permission from T. Yonehara et ai, J. Chem. Phys. 137, 22A520 (2012)).

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