Vitamin B12 carrier proteins and receptors

The Vitamin B12 carrier proteins and receptors constitute a highly specialized system essential for the absorption, transport, and cellular delivery of cobalamin (Vitamin B12) [4, 17]. This multi-step pathway begins with haptocorrin (TCN1) binding B12 in the stomach, followed by the transfer of the vitamin to gastric intrinsic factor (GIF) in the duodenum [16]. The resulting IF-B12 complex is recognized and internalized in the terminal ileum by the cubam receptor, a complex of cubilin (CUBN) and amnionless (AMN) [11, 16]. Once in the bloodstream, B12 is primarily carried by transcobalamin II (TCN2) to peripheral tissues, where it enters cells via the transcobalamin receptor (CD320) through receptor-mediated endocytosis [23, 24]. Dysfunctions in this system, such as the production of anti-intrinsic factor antibodies or genetic mutations in CUBN or TCN2, lead to clinical conditions including pernicious anemia and Imerslund-Gräsbeck syndrome [17, 18]. Beyond its physiological role, this transport machinery is a significant focus in drug development, where B12 is utilized as a targeting ligand to enhance the oral bioavailability of drugs or to deliver cytotoxic agents to CD320-overexpressing cancer cells [3, 7, 13].

Other names

Cobalamin transport systemTranscobalaminsIntrinsic factor systemB12 transport machineryVitamin B12 binding proteins

Binding and transport of cobalamin; receptor-mediated endocytosis via the cubam complex and CD320 receptor [11, 24]