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Haptocorrin

Protein-coding gene in the species Homo sapiens

Protein-coding gene in the species Homo sapiens

Haptocorrin (HC) (also known as transcobalamin-1 (TC-1), or cobalophilin) is a transcobalamin glycoprotein that in humans is encoded by the gene. It is essential to protect the acid-sensitive vitamin B12 from degradation while in the stomach. It is also present in the serum where it binds most circulating vitamin B12, rendering it unavailable for uptake by cells (this is conjectured to be a circulating storage function).

Function

Digestive

HC is produced by the salivary glands of the oral cavity in response to ingestion of food. Vitamin B12 is highly structural susceptible to denaturation by the acidic environment of the stomach. Haptocorrin has a high affinity for the molecular structure of vitamin B12 forming a haptocorrin–B12 complex that is impervious to stomach acid, enabling it to reach the more alkaline duodenum intact. In the duodenum, pancreatic proteases (a component of pancreatic juice) cleave haptocorrin, releasing vitamin B12. Intrinsic factor (IF) that is secreted by parietal cells of the stomach now binds B12 released from haptocorrin to subsequently enable cubilin receptors of the ileum to take up B12–IF complexes by endocytosis-mediated absorption before B12 is finally released into circulation. Without IF, only 1% of vitamin B12 is ultimately absorbed.

Serum

HC is present in blood serum where it binds 80-90% of circulating B12, rendering it unavailable for cellular uptake by transcobalamin II. This is conjectured to be a circulating storage function.

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 insufficient vitamin bound to transcobalamin II.

References

References

  1. "Entrez Gene: transcobalamin I (vitamin B12 binding protein".
  2. (2006). "Essential Haematology 5e (Essential)". Blackwell Publishing Professional.
  3. (2007). "Haptocorrin in humans". Clinical Chemistry and Laboratory Medicine.
  4. (Aug 2009). "Targeting the cubilin receptor through the vitamin B(12) uptake pathway: cytotoxicity and mechanistic insight through fluorescent Re(I) delivery". Journal of Medicinal Chemistry.
  5. (May 2023). "The complex machinery of human cobalamin metabolism". J Inherit Metab Dis.
  6. (November 2003). "Significance of elevated cobalamin (vitamin B12) levels in blood". Clin Biochem.
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