Gastric intrinsic factor and Transcobalamin II (GIF/TCN2)

Gastric intrinsic factor (GIF) and transcobalamin II (TCN2) are essential transport proteins responsible for the absorption and systemic distribution of Vitamin B12 (cobalamin) (Wikipedia, 2024; NIH, 2021). GIF is a glycoprotein secreted by gastric parietal cells that binds dietary B12 in the duodenum, facilitating its uptake in the terminal ileum via the cubam receptor complex (Britannica, 2024; StatPearls, 2023). Once in the circulation, B12 is primarily transported by TCN2, which delivers the vitamin to tissues through receptor-mediated endocytosis via the CD320 receptor (PNAS, 2006; NIH, 2022). Deficiencies in these proteins, often due to autoimmune conditions like pernicious anemia or genetic mutations, lead to megaloblastic anemia and severe neurological impairment (NIH, 2021; ResearchGate, 2021). In clinical practice, these proteins are targeted through the administration of various cobalamin forms (e.g., cyanocobalamin) to bypass or supplement the transport system (StatPearls, 2023). Additionally, the TCN2-B12 pathway is being explored for targeted drug delivery in cancer due to the high expression of its receptor in proliferating cells (NIH, 2022).

Other names

Intrinsic factorTranscobalamin IICBLIFTCN2HaptocorrinTCN1Cobalamin-binding intrinsic factorR-binderVitamin B12 transport proteins

Binding and transport of Vitamin B12 to facilitate intestinal absorption and cellular uptake via receptor-mediated endocytosis.