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Vitamin B12-dependent enzymatic reactions

Molecular classification
Enzyme, Isomerase, Methyltransferase, Hydrolase, Reductive dehalogenase
01

Overview

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).

Other names
B12-dependent enzymesCobalamin-dependent enzymesAdoCbl enzymesMeCbl enzymesDehalogenases
02

Mechanism of action

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.

03

Biological functions

Amino acid metabolismOne-carbon metabolismDNA methylationFatty acid metabolismDegradation of halogenated compounds
04

Disease associations

Inherited metabolic disorders: Deficiencies in B12-dependent enzymes cause methylmalonic aciduria and homocystinuriaCardiovascular disease: Homocysteine elevationNeurodegenerative disease: B12 deficiency can lead to neurological disordersOther: Potential roles in cancer, anemia, immune system dysfunction
05

Safety considerations

B12 supplementation is generally safe; rare hypersensitivityThe main therapeutic challenge is effective delivery/absorption in deficiency states (e.g., pernicious anemia)No major safety concerns for targeting these enzymes therapeutically.
06

Interacting drugs

Vitamin B12 (cobalamin) supplementation

3 more in the full profile.

07

Biomarkers

Methylmalonic acid (for MCM deficiency)Homocysteine (for MS deficiency)Serum vitamin B12Serum holo-transcobalamin

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