Transcobalamin Explained

Transcobalamins are carrier proteins which bind cobalamin (B12).

Types

Transcobalamin I (TC-1), also known as haptocorrin (HC), R-factor, and R-protein is encoded in the human by the TCN1 gene. TC-1 is a glycoprotein produced by the salivary glands of the mouth. It primarily serves to protect cobalamin (Vitamin B12) from acid degradation in the stomach by producing a HC-Vitamin B12 complex. Once the complex has traveled to the more pH-neutral duodenum, pancreatic proteases degrade haptocorrin, releasing free cobalamin, which now binds to intrinsic factor for absorption by ileal enterocytes.

Separate from the digestive absorption function, serum TC-1 binds 80-90% of circulating B12, rendering it unavailable for cellular delivery by TC-2.[1] Several serious, even life-threatening diseases cause elevated serum HC, measured as abnormally high serum vitamin B12.[2]

Transcobalamin II (TC-2), a nonglycoprotein secretory protein of molecular mass 43 kDa, is encoded in the human by the TCN2 gene. TC-2 binds cobalamin once it has been taken up by enterocytes of the terminal ileum and the "Intrinsic Factor-Vitamin B12" complex has been degraded. TC-2 is then involved with the transport of Vitamin B12 to the tissues, where it binds to its plasma membrane receptor (TC-2R), a heavily glycosylated protein with a monomeric molecular mass of 62 kDa, and releases cobalamin to the cells.[3]

Notes and References

  1. McCorvie TJ, Ferreira D, Yue WW, Froese DS . The complex machinery of human cobalamin metabolism . J Inherit Metab Dis . 46 . 3 . 406–20 . May 2023 . 36680553 . 10.1002/jimd.12593 .
  2. Ermens AA, Vlasveld LT, Lindemans J . Significance of elevated cobalamin (vitamin B12) levels in blood . Clin Biochem . 36 . 8 . 585–90 . November 2003 . 14636871 . 10.1016/j.clinbiochem.2003.08.004 .
  3. Seetharam B, Li N . Transcobalamin II and its cell surface receptor . Vitam Horm . 59 . 337–66 . 2000 . 10714245 . 10.1016/s0083-6729(00)59012-8 .