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Vitamin B12-dependent enzyme

Molecular classification
Enzyme, Isomerase, Methyltransferase, Dehalogenase, Organometallic cofactor-containing protein
01

Overview

Vitamin B12-dependent enzymes are a diverse family of proteins that require the organometallic cofactor cobalamin (vitamin B12) for catalytic activity. They fall into three main subfamilies based on their reaction chemistry: adenosylcobalamin-dependent isomerases, which catalyze radical-mediated rearrangements; methylcobalamin-dependent methyltransferases, which mediate transfer of methyl groups; and dehalogenases found primarily in anaerobic bacteria that catalyze reductive dehalogenation reactions. These enzymes play essential roles in amino acid metabolism, fatty acid breakdown, DNA synthesis, and detoxification pathways. Defects in individual members cause serious human diseases including megaloblastic anemia and inherited metabolic disorders such as methylmalonic acidemia and homocystinuria. While not themselves drug targets in the traditional sense outside rare cases like bacterial dehalogenases exploited biotechnologically, their function depends critically on adequate levels of dietary or supplemental vitamin B12.

Other names
Cobalamin-dependent enzymeCoenzyme B12-dependent enzymeCobalamin enzymeB12-enzyme
02

Mechanism of action

For drugs/supplements like vitamin B12 itself: Cofactor replacement for defective or deficient enzymatic activity. For potential inhibitors/antagonists (rare): Competitive inhibition at the cobalamin-binding site.

03

Biological functions

Catalysis of radical-based rearrangement reactions (isomerases)Methyl group transfer reactions (methyltransferases)Reductive dehalogenation of halogenated compounds in bacteriaAmino acid metabolism, fatty acid metabolism, DNA synthesis
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Disease associations

Inborn errors of metabolism such as methylmalonic acidemia and homocystinuria due to defects in specific B12-dependent enzymesNeurological disorders associated with vitamin B12 deficiencyMegaloblastic anemia due to impaired DNA synthesis from defective methionine synthase activity
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Safety considerations

Over-supplementation of vitamin B12 is generally considered safe but may mask other deficiencies.Inhibition or loss-of-function mutations can lead to severe metabolic and neurological disease.
06

Interacting drugs

Vitamin B12 supplements
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Biomarkers

Elevated methylmalonic acid for methylmalonyl-CoA mutase deficiency.Elevated homocysteine for methionine synthase deficiency.

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