The role of cobalt as a cofactor is limited to its presence in vitamin B12. Cobalt can exist in three valence states, Co+, Co2+, and Co3+ with Co2+ being the most common in 5' deoxyadenosylcobala-min, the familiar form of vitamin B12 coenzyme. Cobalt is bound by a planar ring system analogous to heme but with very special features (see 00059). Cobalt and nickel are ions that may have figured more prominently in primitive systems when the atmosphere contained H2 and CH4 as common environmental gases. The argument has been made that as biological systems gradually adapted to O2 the necessity for these two metals became less.
Reactivity Cobalt in the structure of vitamin B12 resembles iron in heme by being bound in a square planar arrangement to a ring (corrin). Unlike heme, however, cobalt has two axial ligands that are free from the protein, which allows nonprotein groups to access the central metal from above and below the plane. In the octahedral complex, one axial position (the fifth coordinate) is normally occupied by a ben-zimidazole and the other by a methyl group (as in methyl cobalamin). The arrangement is unique and allows cobalt to form carbon-metal bonds with the potential for two different reactivities. The methyl group, for example, may be removed as a carbonium ion retaining both electrons on the cobalt, which then reverts to a less stable Co(I). This is typical of the reaction in which vitamin B12 acts as a methyl donor. In positional rearrangements, cobalt retains only one electron and forms a stable Co(II) or d7 ion with the release of a free radical. Free radicals are highly reactive and overcome energy barriers that would stymie other reactants. Thus, cobalt's chemical properties transfer groups as carbonium ions or highly reactive carbon-centered radicals. Both products are possible and hence explains the necessity for cobalt as a cofactor for a reaction that proceeds via a free radical mechanism. An example of the latter is the intramolecular rearrangement of methyl-malonyl-CoA to succinyl-CoA as catalyzed by methylmalonyl-CoA mutase.
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