Haptocorrin Explained

Haptocorrin (HC) also known as transcobalamin-1 (TC-1) or cobalophilin is a transcobalamin protein that in humans is encoded by the gene.[1] One essential function of haptocorrin is protection of the acid-sensitive vitamin B12 while it moves through the stomach. A second function is serum HC binding of the great majority of circulating vitamin B12, rendering it unavailable for take-up by cells. This is conjectured to be a circulating storage function.

Functions

Haptocorrin (HC), also commonly known as the R-protein, or the R-factor, or previously referred to as transcobalamin I, is a unique glycoprotein produced by the salivary glands of the oral cavity, in response to ingestion of food. This protein binds strongly to vitamin B12 in what is an intricate and necessary mechanism to protect this vitamin from the acidic environment of the stomach.[2] Vitamin B12 is an essential water-soluble vitamin, the deficiency of which creates anemia (macrocytic anemia), decreased bone marrow cell production (anemia, pancytopenia), neurological problems, as well as metabolic issues (methylmalonyl-CoA acidosis).[2]

Vitamin B12 is therefore an important vitamin for the body to absorb. Despite its vital role however, vitamin B12 is structurally very sensitive to the hydrochloric acid found in the stomach secretions, and easily denatures in that environment before it has a chance to be absorbed by the small intestine. Found in fresh animal products (such as liver), vitamin B12 attaches haptocorrin, which has a high affinity for its molecular structure.[3] Coupled together vitamin B12 and haptocorrin create a complex. This haptocorrin–B12 complex is impervious to the insult of the stomach acid, and passes on via the pylorus to the duodenum. In the duodenum pancreatic proteases (a component of pancreatic juice) cleave haptocorrin, releasing vitamin B12 in its free form.

The same cells in the stomach that produce gastric hydrochloric acid, the parietal cells, also produce a molecule called the intrinsic factor (IF), which binds the B12 after its release from haptocorrin by digestion, and without which only 1% of vitamin B12 is absorbed. Intrinsic factor (IF) is a glycoprotein, with a molecular weight of 45 kDa. In the duodenum, the free vitamin B12 attaches to the intrinsic factor (IF) to create a vitamin B12–IF complex. This complex then travels through the small bowel and reaches the terminal tertiary portion of the small intestine, called the ileum. The ileum is the longest of all portions of the small intestine, and has on its surface specialized receptors called cubilin receptors, that identify the B12–IF complexes and take them up into the circulation via endocytosis-mediated absorption.[4]

Separate from the digestive absorption function, serum HC binds 80-90% of circulating B12, rendering it unavailable for cellular delivery by transcobalamin II. This is conjectured to be a circulating storage function.[5] Several serious, even life-threatening diseases cause elevated serum HC, measured as abnormally high serum vitamin B12 while at the same time manifesting as a vitamin deficiency because of insufficent vitamin bound to transcobalamin II.[6]

Further reading

Notes and References

  1. Web site: Entrez Gene: transcobalamin I (vitamin B12 binding protein.
  2. Book: Pettit . John D. . Paul . Moss . Essential Haematology 5e (Essential) . Blackwell Publishing Professional . 2006 . 44 . 1-4051-3649-9 .
  3. Morkbak AL, Poulsen SS, Nexo E . Haptocorrin in humans . Clinical Chemistry and Laboratory Medicine . 45 . 12 . 1751–9 . 2007 . 17990953 . 10.1515/CCLM.2007.343 . 24204285 .
  4. Viola-Villegas N, Rabideau AE, Bartholomä M, Zubieta J, Doyle RP . Targeting the cubilin receptor through the vitamin B(12) uptake pathway: cytotoxicity and mechanistic insight through fluorescent Re(I) delivery . Journal of Medicinal Chemistry . 52 . 16 . 5253–61 . Aug 2009 . 19627091 . 10.1021/jm900777v .
  5. 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 .
  6. 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 .

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