Vitamin B12 transport and carrier proteins

Vitamin B12 transport and carrier proteins constitute a specialized multi-protein system essential for the absorption, systemic circulation, and cellular uptake of cobalamin (Vitamin B12). The system primarily involves three binding proteins: Haptocorrin (TCN1), which protects B12 in the stomach; Intrinsic Factor (GIF), which facilitates absorption in the ileum; and Transcobalamin II (TCN2), which delivers the vitamin to peripheral tissues via the CD320 receptor (Nielsen et al., 2012). This pathway is critical because humans cannot synthesize B12 and must rely on efficient transport to support DNA synthesis and neurological function (Mucha et al., 2021). Defects in these proteins or their receptors lead to severe clinical conditions such as pernicious anemia and megaloblastic anemia. Therapeutically, these proteins are targeted for B12 supplementation and are increasingly explored as vehicles for the targeted delivery of drugs and imaging agents, particularly in oncology where B12 receptors are often overexpressed (Gupta et al., 2008). Recent research also highlights the importance of these transport proteins as biomarkers for subclinical deficiency and cognitive decline (Green et al., 2025).

Other names

TranscobalaminsCobalamin-binding proteinsR-bindersVitamin B12-binding proteinsCobalamin transport system

Sequential binding and transport of cobalamin through the gastrointestinal tract and bloodstream, followed by receptor-mediated endocytosis into target cells via specific receptors like CD320 and the Cubam complex.