Cobalamin = vitamin B12. Absorption: dietary B12 in protein binds INTRINSIC FACTOR (IF, gastric parietal cells) in duodenum → IF-B12 complex absorbed at terminal ileum via cubilin/AMN receptor. Two coenzymes: methylcobalamin (methionine synthase cofactor, see methionine_sam_cycle) and adenosylcobalamin (methylmalonyl-CoA mutase cofactor, propionate catabolism). Deficiency causes: megaloblastic anemia (impaired DNA synthesis via THF trap), subacute combined degeneration of the spinal cord (impaired myelin maintenance from methylmalonate accumulation), hyperhomocysteinemia. Causes: pernicious anemia (autoimmune anti-IF antibodies), atrophic gastritis, terminal ileum disease/resection, strict vegan diet without supplementation. Treatment: IM cyanocobalamin (1000 µg monthly) or high-dose oral; underlying cause-specific.
Organ Systems
immune-hematologic
nervous
digestive
Pathway Steps
cobalamin → methylcobalamin — via methionine synthase reductase + MTRR. Methylcobalamin is the cytosolic cofactor for methionine synthase (homocysteine → methionine); MTRR keeps the cobalamin reduced. Defects here or dietary B12 deficiency impair remethylation, raising homocysteine and causing megaloblastic anemia plus the methyl-folate trap.
cobalamin → adenosylcobalamin — via mitochondrial adenosylation (MMAA/MMAB). Adenosylcobalamin is the mitochondrial cofactor for methylmalonyl-CoA mutase (propionate → succinyl-CoA). Its deficiency raises methylmalonic acid (MMA) — a sensitive, B12-specific early marker (unlike homocysteine, which also rises in folate deficiency).
Known Modulators
cyanocobalamin (substrate) — B12 (cyanide-stabilized synthetic). most common supplement form; converted to methyl/adeno-cobalamin in tissues
hydroxocobalamin (substrate) — B12 (hydroxy form). IM B12; cyanide antidote (forms cyanocobalamin); preferred for elderly with low B12