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The "Vitamin B12 pathway" encompasses the coordinated actions of proteins and enzymes that enable the absorption, transport, intracellular utilization, and recycling of vitamin B12 (cobalamin). Dietary B12 is released from proteins in food by gastric acid and proteases, binds first to haptocorrin (also called R-binder), and then to intrinsic factor (produced by parietal cells). The vitamin B12–intrinsic factor complex is absorbed in the terminal ileum via receptor-mediated endocytosis involving cubam (cubilin/amnionless complex). After absorption, B12 is transferred to transcobalamin II and distributed to tissues, where it serves as a cofactor for methionine synthase (required for methylation reactions and DNA synthesis) and methylmalonyl-CoA mutase (required for odd-chain fatty acid and amino acid metabolism). Deficiencies or inborn errors affecting any step may cause megaloblastic anemia, neuropathy, and other disease states. Because this is a collection of processes involving multiple molecular targets rather than a single protein or defined target, it is not considered a canonical molecular target for drug discovery but rather a biological pathway.
Supplementation supplies the cofactor for essential enzymes: Methionine synthase (methylates homocysteine to methionine, using methylcobalamin) Methylmalonyl-CoA mutase (converts methylmalonyl-CoA to succinyl-CoA, using adenosylcobalamin)
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