Cobalamin-dependent enzymes involved in DNA synthesis and repair

Cobalamin-dependent enzymes, also known as Vitamin B12-dependent enzymes, play essential roles in DNA synthesis and repair, primarily through two major pathways: (1) the conversion of homocysteine to methionine via methionine synthase, enabling the provision of methyl groups for DNA methylation and nucleotide biosynthesis, and (2) the generation of deoxyribonucleotides from ribonucleotides via ribonucleotide reductase class II, which uses cobalamin-derived radicals for DNA precursor synthesis[1][5][6][9]. These enzymes require the cobalamin (B12) cofactor, which mediates radical chemistry or methyl group transfer, and defects or deficiencies in these enzymes or their cofactor can result in impaired DNA replication, increased DNA damage, megaloblastic anemia, and heightened risk for cancer and neurological disease[5][9]. Many of these enzymes, such as methionine synthase, methylmalonyl-CoA mutase, and certain radical SAM methylases, are essential for maintaining genome integrity and cell division, making them important—though indirect—therapeutic targets or biomarkers in diseases related to DNA damage and repair[1][5][6][7][9]. **Note:** This target as stated is *not* a single molecule but rather a generalization of multiple enzyme classes and pathways (e.g., methionine synthase, methylmalonyl-CoA mutase, class II ribonucleotide reductase, radical SAM methyltransferases)[1][5][6][9]. For drug discovery or clinical utility, targets should be listed individually by their specific enzyme names rather than as an aggregate pathway. Therefore, the provided name "DNA synthesis/repair pathways via cobalamin-dependent enzymes" is overly broad and not a canonical single target, and would be marked as *is_incorrect: true*, recommending specification of individual enzyme targets for structured information extraction.

Other names

Cobalamin-dependent enzymesVitamin B12-dependent enzymesB12-dependent enzymesCobalamin-utilizing enzymesCoenzyme B12-dependent enzymes

Cofactor supplementation restores enzyme activity (for B12-responsive conditions); Radical generation for chemical transformations; Methyl group transfer (e.g., DNA methylation)