B12dependent

B12dependent refers to enzymes that require cobalamin, also known as vitamin B12, as a cofactor to perform their catalytic reactions. The B12 cofactor exists in two reactive forms used by different enzyme families: methylcobalamin, which participates in methyl transfer reactions, and adenosylcobalamin (AdoCbl), which mediates radical-based rearrangements.

Mechanism and forms: In methyltransferases such as methionine synthase, a methyl group is transferred from a folate-derived donor to homocysteine to form methionine, with cobalamin cycling between its methylated and unreduced states. In adenosylcobalamin-dependent enzymes, such as methylmalonyl-CoA mutase and certain ribonucleotide reductases, homolytic cleavage of the Co–C bond generates a 5'-deoxyadenosyl radical that initiates substrate rearrangements or transformations.

Examples and roles: Key B12dependent enzymes include methionine synthase (MetH), important for methionine and folate metabolism; methylmalonyl-CoA mutase (MCM), involved in propionate catabolism; and ribonucleotide reductase class II, which uses B12 in DNA precursor synthesis. Additional B12-dependent enzymes are found in various anaerobic bacteria, including some diol and glycerol dehydratases.

Distribution, health, and nutrition: B12dependent enzymes are widespread in bacteria and archaea and are present in some eukaryotes, including humans. Humans cannot synthesize vitamin B12 and must obtain it from diet; intrinsic factor–mediated intestinal absorption is required. Deficiency can disrupt methionine and odd-chain fatty acid metabolism, potentially leading to methylmalonic aciduria, homocystinuria, neuropathy, and anemia. Some gut microbes synthesize B12, though its availability to the host is limited.

See also: cobalamin, vitamin B12, coenzyme B12, cobalamin-dependent enzymes.