Haptocorrin

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Haptocorrin (HC) (also known as transcobalamin-1 (TC-1), or cobalophilin) is a transcobalamin glycoprotein that in humans is encoded by the TCN1 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.

Further reading

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• Garrod MG, Allen LH, Haan MN, Green R, Miller JW (May 2010). "Transcobalamin C776G genotype modifies the association between vitamin B12 and homocysteine in older Hispanics". European Journal of Clinical Nutrition. 64 (5): 503–509. doi:10.1038/ejcn.2010.20. PMC 2864787. PMID 20216556.
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• Matteini AM, Walston JD, Bandeen-Roche K, Arking DE, Allen RH, Fried LP, et al. (Jan 2010). "Transcobalamin-II variants, decreased vitamin B12 availability and increased risk of frailty". The Journal of Nutrition, Health & Aging. 14 (1): 73–77. doi:10.1007/s12603-010-0013-1. PMC 3042247. PMID 20082058.
• Lee KM, Lan Q, Kricker A, Purdue MP, Grulich AE, Vajdic CM, et al. (Dec 2007). "One-carbon metabolism gene polymorphisms and risk of non-Hodgkin lymphoma in Australia". Human Genetics. 122 (5): 525–533. doi:10.1007/s00439-007-0431-2. PMID 17891500. S2CID 21487646.
• Liu T, Qian WJ, Gritsenko MA, Camp DG, Monroe ME, Moore RJ, et al. (2005). "Human plasma N-glycoproteome analysis by immunoaffinity subtraction, hydrazide chemistry, and mass spectrometry". Journal of Proteome Research. 4 (6): 2070–2080. doi:10.1021/pr0502065. PMC 1850943. PMID 16335952.
• Fintelman-Rodrigues N, Corrêa JC, Santos JM, Pimentel MM, Santos-Rebouças CB (2009). "Investigation of CBS, MTR, RFC-1 and TC polymorphisms as maternal risk factors for Down syndrome". Disease Markers. 26 (4): 155–161. doi:10.1155/2009/504625. PMC 3833707. PMID 19729796.
• Wang SS, Maurer MJ, Morton LM, Habermann TM, Davis S, Cozen W, et al. (Mar 2009). "Polymorphisms in DNA repair and one-carbon metabolism genes and overall survival in diffuse large B-cell lymphoma and follicular lymphoma". Leukemia. 23 (3): 596–602. doi:10.1038/leu.2008.240. PMC 3066015. PMID 18830263.
• Fedosov SN, Fedosova NU, Kräutler B, Nexø E, Petersen TE (May 2007). "Mechanisms of discrimination between cobalamins and their natural analogues during their binding to the specific B12-transporting proteins". Biochemistry. 46 (21): 6446–6458. doi:10.1021/bi062063l. PMID 17487979.
• Carmel R, Parker J, Kelman Z (Nov 2009). "Genomic mutations associated with mild and severe deficiencies of transcobalamin I (haptocorrin) that cause mildly and severely low serum cobalamin levels". British Journal of Haematology. 147 (3): 386–391. doi:10.1111/j.1365-2141.2009.07855.x. PMID 19686235. S2CID 20530258.
• Talmud PJ, Drenos F, Shah S, Shah T, Palmen J, Verzilli C, et al. (Nov 2009). "Gene-centric association signals for lipids and apolipoproteins identified via the HumanCVD BeadChip". American Journal of Human Genetics. 85 (5): 628–642. doi:10.1016/j.ajhg.2009.10.014. PMC 2775832. PMID 19913121.
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• von Castel-Dunwoody KM, Kauwell GP, Shelnutt KP, Vaughn JD, Griffin ER, Maneval DR, et al. (Jun 2005). "Transcobalamin 776C->G polymorphism negatively affects vitamin B-12 metabolism". The American Journal of Clinical Nutrition. 81 (6): 1436–1441. doi:10.1093/ajcn/81.6.1436. PMID 15941899.
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