Gastric intrinsic factor (GIF) and Transcobalamin II (TCN2) (GIF/TCN2)

Gastric intrinsic factor (GIF) and Transcobalamin II (TCN2) are essential glycoproteins that mediate the absorption and systemic distribution of Vitamin B12 (cobalamin). GIF is secreted by gastric parietal cells and binds to dietary B12 in the small intestine, enabling its uptake in the terminal ileum via the cubam receptor complex (StatPearls, NBK441923). Once in the circulation, B12 is primarily bound by TCN2 to form holotranscobalamin, which delivers the vitamin to peripheral tissues through receptor-mediated endocytosis via the CD320 receptor (UniProt, P20062). These proteins are vital for maintaining normal erythropoiesis and neurological health, as B12 is a co-factor for DNA synthesis and myelin maintenance. Clinical conditions such as pernicious anemia involve the autoimmune destruction of GIF or parietal cells, leading to severe B12 deficiency and megaloblastic anemia (PubMed, PMID: 28223726). Therapeutic strategies focus on the administration of cobalamin supplements, such as cyanocobalamin, which rely on these transport proteins for efficacy or utilize high-dose passive diffusion when the transport system is compromised (PubMed, PMID: 23116300).

Other names

Intrinsic factorIFGastric intrinsic factorTCN2TCIITranscobalamin-2Cobalamin binding protein

Binding and facilitating the intestinal absorption and systemic transport of Vitamin B12 (cobalamin) to ensure cellular availability for DNA synthesis and neurological function.