Haptocorrin also known as transcobalamin-1 (TC-1) or cobalophilin is a transcobalaminprotein that in humans is encoded by the TCN1gene. The essential function of haptocorrin is protection of the acid-sensitive vitamin B12 while it moves through the stomach.
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.:44 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).:50–51
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. 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.
In short, the essential function of haptocorrin is protection of the acid-sensitive vitamin B12 while it moves through the stomach. Haptocorrin also circulates and binds approximately 80% of circulating B12, rendering it unavailable for cellular delivery by transcobalamin II
^Viola-Villegas N, Rabideau AE, Bartholomä M, Zubieta J, Doyle RP (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. 52 (16): 5253–61. doi:10.1021/jm900777v. PMID19627091.
^Vitamin B12 Deficiency Sally P. Stabler, M.D" N Engl J Med 2013; 368:149-160 January 10, 2013
Guéant-Rodriguez RM, Juilliére Y, Candito M, Adjalla CE, Gibelin P, Herbeth B, Van Obberghen E, Gueánt JL (Sep 2005). "Association of MTRRA66G polymorphism (but not of MTHFR C677T and A1298C, MTRA2756G, TCN C776G) with homocysteine and coronary artery disease in the French population". Thrombosis and Haemostasis. 94 (3): 510–5. doi:10.1160/TH05-04-0262. PMID16268464.
Lee KM, Lan Q, Kricker A, Purdue MP, Grulich AE, Vajdic CM, Turner J, Whitby D, Kang D, Chanock S, Rothman N, Armstrong BK (Dec 2007). "One-carbon metabolism gene polymorphisms and risk of non-Hodgkin lymphoma in Australia". Human Genetics. 122 (5): 525–33. doi:10.1007/s00439-007-0431-2. PMID17891500.
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): 155–61. doi:10.3233/DMA-2009-0626. PMID19729796.
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): 6446–58. doi:10.1021/bi062063l. PMID17487979.
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): 386–91. doi:10.1111/j.1365-2141.2009.07855.x. PMID19686235.
Collin SM, Metcalfe C, Refsum H, Lewis SJ, Smith GD, Cox A, Davis M, Marsden G, Johnston C, Lane JA, Donovan JL, Neal DE, Hamdy FC, Smith AD, Martin RM (Nov 2010). "Associations of folate, vitamin B12, homocysteine, and folate-pathway polymorphisms with prostate-specific antigen velocity in men with localized prostate cancer". Cancer Epidemiology, Biomarkers & Prevention. 19 (11): 2833–8. doi:10.1158/1055-9965.EPI-10-0582. PMID20852008.
Geisel J, Hübner U, Bodis M, Schorr H, Knapp JP, Obeid R, Herrmann W (Nov 2003). "The role of genetic factors in the development of hyperhomocysteinemia". Clinical Chemistry and Laboratory Medicine. 41 (11): 1427–34. doi:10.1515/CCLM.2003.219. PMID14656021.
Martinelli M, Scapoli L, Palmieri A, Pezzetti F, Baciliero U, Padula E, Carinci P, Morselli PG, Carinci F (Mar 2006). "Study of four genes belonging to the folate pathway: transcobalamin 2 is involved in the onset of non-syndromic cleft lip with or without cleft palate". Human Mutation. 27 (3): 294. doi:10.1002/humu.9411. PMID16470748.
von Castel-Dunwoody KM, Kauwell GP, Shelnutt KP, Vaughn JD, Griffin ER, Maneval DR, Theriaque DW, Bailey LB (Jun 2005). "Transcobalamin 776C->G polymorphism negatively affects vitamin B-12 metabolism". The American Journal of Clinical Nutrition. 81 (6): 1436–41. PMID15941899.
Oh JH, Yang JO, Hahn Y, Kim MR, Byun SS, Jeon YJ, Kim JM, Song KS, Noh SM, Kim S, Yoo HS, Kim YS, Kim NS (Dec 2005). "Transcriptome analysis of human gastric cancer". Mammalian Genome. 16 (12): 942–54. doi:10.1007/s00335-005-0075-2. PMID16341674.
Ramachandran P, Boontheung P, Xie Y, Sondej M, Wong DT, Loo JA (Jun 2006). "Identification of N-linked glycoproteins in human saliva by glycoprotein capture and mass spectrometry". Journal of Proteome Research. 5 (6): 1493–503. doi:10.1021/pr050492k. PMID16740002.