cobalaminbinding

Cobalamin binding refers to the selective, high-affinity interaction of cobalamin (vitamin B12) with specialized proteins that sequester, protect, transport, store, or deliver the vitamin within organisms. Binding proteins influence the stability, distribution, and bioavailability of cobalamin and are involved in digestion, systemic transport, cellular uptake, and regulation of cobalamin-dependent pathways.

In humans, dietary B12 is released from dietary proteins in the stomach and binds to intrinsic factor (IF), a glycoprotein produced by parietal cells. The IF-B12 complex is resistant to degradation in the stomach and binds to a receptor formed by cubilin and amnionless in the ileum, enabling endocytosis. Inside intestinal cells, B12 is released and then enters the circulation, where it binds to transcobalamin II (TC II) to form holo-transcobalamin, the biologically active fraction that delivers B12 to cells via receptor-mediated uptake. A second set of B12-binding proteins, haptocorrin (transcobalamins I and III, TC I/III), binds B12 in saliva and blood but generally does not mediate cellular delivery; these complexes act as storage or transport pools and are degraded to release B12 in tissues or the gut. Defects in intrinsic factor or the ileal receptor can cause pernicious anemia or B12 malabsorption.

Outside humans, many bacteria and archaea possess cobalamin-binding proteins involved in uptake and trafficking of B12 to metalloenzymes. Structural studies show diverse B12-binding pockets that coordinate cobalt and the lower ligand, with variations in base-off/base-on configurations. Clinically, holo-transcobalamin is used as a biomarker of available B12, reflecting the fraction that can be delivered to cells.