Is it SAM the Methyl Man? B12
Methylmalonyl-CoA Mutase
catalyzes a molecular rearrangement in which the branched carbon chain
of methylmalonyl-CoA is converted tothe linear carbon chain of
succinyl-CoA. The carboxyl that is in ester linkageto the thiol of coenzyme A is shifted to an adjacent carbon atom, with opposite shift of ahydrogen atom.
Recall that coenzyme A is a large molecule, as shown at right.

Coenzyme B12 (vitamin B12, also called cobalamin) is the prosthetic group of Methylmalonyl-CoA Mutase. In mammals coenzyme B12 is a cofactor for this reaction and is involved also in methyl group transfer. In bacteria, coenzyme B12 is involved in a larger variety of carbon-skeleton rearrangement and elimination reactions.
Coenzyme B12
bound to Methylmalonyl-CoA Mutase is displayed at right in ball and
stick display, with the cobalt atom in spacefill display. See also
diagrams in the Stadtman website at NIH and in the Voet & Voet textbook pages 922-927. Coenzyme B12 contains a heme-like corrinring with a cobalt ion coordinated to 4ring nitrogen atoms.
In free vitamin B12, the cobalt atom has two axial ligands: a ring N atom of dimethylbenzimidazole (covalently linked to the corrin ring, shown above extended away from the Co), and the methyl C atom of 5'-deoxyadenosine (not shown here).
When coenzyme B12
is bound to the Methylmalonyl CoA Mutase enzyme, the
dimethylbenzimidazole ligand extends away from the Co is replaced by an
enzyme histidine N.

Color key: C O N P Co
Homolytic cleavage of the deoxyadenosyl C-Co bond yields a deoxyadenosyl carbonradical as Co3+ becomes Co2+.
Reaction of this with methylmalonyl-CoA generates a radical
substrateintermediate and 5'-deoxyadenosine. Following rearrangement of
the substrate, the product radical abstracts a hydrogen atom from the
methyl group of 5'-deoxyadenosine. This yield succinyl-CoA and the
5'-deoxyadenosyl radical, which reacts with coenzyme B12 to reestablish the deoxyadenosyl C-Co bond. Explore
at right Methylmalonyl-CoA Mutase, with desulfo-coenzyme A (CoA analog
lacking the reactive thiol) present at the active site.

Methylmalonyl-CoA
Mutase
Vitamin B12is synthesized only by bacteria. Ruminant animals obtain the vitamin frombacteria in their digestive system. Humans obtain vitamin B12 from meat or dairyproducts. Vitamin B12 is absorbed by cells in the upper part ofthe human small intestine, via receptor-mediated endocytosis. Vitamin B12 synthesizedby bacteria in the large intestine is unavailable. Strict vegetarians eventuallybecome deficient in vitamin B12.