Transcobalamins

Transcobalamins are a family of vitamin B12 (cobalamin) binding transport proteins found in vertebrates. They circulate in blood and extracellular fluids and carry cobalamin from absorption sites to tissues that require it. In humans, three transcobalamins have been described: transcobalamin I (TCN1, also called haptocorrin), transcobalamin II (TCN2, or transcobalamin II), and transcobalamin III (TCN3).

Transcobalamin II is the main transporter delivering cellular B12. In plasma it forms holo-transcobalamin II by binding a molecule of cobalamin; this complex binds to the transcobalamin receptor CD320 on the surface of cells, is endocytosed, and the vitamin is released for intracellular processing into methylcobalamin or adenosylcobalamin, the active cofactors required by cobalamin-dependent enzymes. Holo-transcobalamin II is considered the biologically active fraction of circulating B12.

Transcobalamin I (haptocorrin) binds a large proportion of circulating corrinoids, including cobalamin, but does not participate directly in cellular delivery. It is secreted by various tissues and is also present in saliva, where it can protect B12 from degradation in the stomach. The exact role of transcobalamin III is less well defined; it is detected in plasma in some species, including humans, and is thought to be a secondary carrier with unclear significance for cellular uptake.

Clinical relevance: total serum B12 status is commonly measured, but the holo-transcobalamin II fraction reflects the portion available to cells and can be a more sensitive early indicator of deficiency. Genetic defects affecting transcobalamin II cause severe, early-onset cobalamin deficiency with hematologic and neurological manifestations.

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