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Vitamin B12-dependent enzymatic reactions are mediated by enzymes that use vitamin B12 (cobalamin) as an essential cofactor. There are three main classes in animals: adenosylcobalamin-dependent isomerases, methylcobalamin-dependent methyltransferases, and, in bacteria, reductive dehalogenases. These enzymes catalyze pivotal reactions in amino acid metabolism, fatty acid breakdown, and DNA methylation, as well as the degradation of halogenated environmental toxins in microbes. B12-dependent enzymes function via unique radical or nucleophilic mechanisms involving the cleavage of the cobalt-carbon bond in the vitamin B12 cofactor. Deficiency or genetic defects in these enzymes lead to serious metabolic disorders, notably methylmalonic aciduria (MCM) and homocystinuria (MS).
Drugs (cobalamin derivatives) act as cofactors, restoring enzymatic function in cases of B12 deficiency. These enzymes use radical chemistry (adenosylcobalamin-dependent) or methyl transfer (methylcobalamin-dependent) to facilitate their reactions.
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