Biology:Haptocorrin
Haptocorrin also known as transcobalamin-1 (TC-1) or cobalophilin is a transcobalamin protein that in humans is encoded by the TCN1 gene.[1] The essential function of haptocorrin is protection of the acid-sensitive vitamin B12 while it moves through the stomach.
Function
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]: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).[2]: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.[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]
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.[5]
References
- ↑ "Entrez Gene: transcobalamin I (vitamin B12 binding protein". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=6947.
- ↑ Jump up to: 2.0 2.1 Pettit, John D.; Moss, Paul (2006). Essential Haematology 5e (Essential). Blackwell Publishing Professional. pp. 44. ISBN 1-4051-3649-9.
- ↑ "Haptocorrin in humans". Clinical Chemistry and Laboratory Medicine 45 (12): 1751–9. 2007. doi:10.1515/CCLM.2007.343. PMID 17990953.
- ↑ "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. doi:10.1021/jm900777v. PMID 19627091.
- ↑ "Vitamin B12 deficiency". The New England Journal of Medicine 368 (21): 2041–2. 2013. doi:10.1056/NEJMc1304350. PMID 23697526.
Further reading
- "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. Sep 2005. doi:10.1160/TH05-04-0262. PMID 16268464.
- "Transcobalamin C776G genotype modifies the association between vitamin B12 and homocysteine in older Hispanics". European Journal of Clinical Nutrition 64 (5): 503–9. May 2010. doi:10.1038/ejcn.2010.20. PMID 20216556.
- "Integrative predictive model of coronary artery calcification in atherosclerosis". Circulation 120 (24): 2448–54. Dec 2009. doi:10.1161/CIRCULATIONAHA.109.865501. PMID 19948975.
- "Transcobalamin-II variants, decreased vitamin B12 availability and increased risk of frailty". The Journal of Nutrition, Health & Aging 14 (1): 73–7. Jan 2010. doi:10.1007/s12603-010-0013-1. PMID 20082058.
- "One-carbon metabolism gene polymorphisms and risk of non-Hodgkin lymphoma in Australia". Human Genetics 122 (5): 525–33. Dec 2007. doi:10.1007/s00439-007-0431-2. PMID 17891500. https://zenodo.org/record/1232733.
- "Human plasma N-glycoproteome analysis by immunoaffinity subtraction, hydrazide chemistry, and mass spectrometry". Journal of Proteome Research 4 (6): 2070–80. 2005. doi:10.1021/pr0502065. PMID 16335952.
- "Investigation of CBS, MTR, RFC-1 and TC polymorphisms as maternal risk factors for Down syndrome". Disease Markers 26 (4): 155–61. 2009. doi:10.1155/2009/504625. PMID 19729796.
- "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. Mar 2009. doi:10.1038/leu.2008.240. PMID 18830263.
- "Mechanisms of discrimination between cobalamins and their natural analogues during their binding to the specific B12-transporting proteins". Biochemistry 46 (21): 6446–58. May 2007. doi:10.1021/bi062063l. PMID 17487979.
- "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. Nov 2009. doi:10.1111/j.1365-2141.2009.07855.x. PMID 19686235.
- "Gene-centric association signals for lipids and apolipoproteins identified via the HumanCVD BeadChip". American Journal of Human Genetics 85 (5): 628–42. Nov 2009. doi:10.1016/j.ajhg.2009.10.014. PMID 19913121.
- "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. Nov 2010. doi:10.1158/1055-9965.EPI-10-0582. PMID 20852008.
- "Folic acid use in pregnancy and embryo selection". BJOG 115 (7): 851–6. Jun 2008. doi:10.1111/j.1471-0528.2008.01737.x. PMID 18485163.
- "Genome-wide association study of vitamin B6, vitamin B12, folate, and homocysteine blood concentrations". American Journal of Human Genetics 84 (4): 477–82. Apr 2009. doi:10.1016/j.ajhg.2009.02.011. PMID 19303062.
- "The role of genetic factors in the development of hyperhomocysteinemia". Clinical Chemistry and Laboratory Medicine 41 (11): 1427–34. Nov 2003. doi:10.1515/CCLM.2003.219. PMID 14656021.
- "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. Mar 2006. doi:10.1002/humu.9411. PMID 16470748.
- "Transcobalamin 776C->G polymorphism negatively affects vitamin B-12 metabolism". The American Journal of Clinical Nutrition 81 (6): 1436–41. Jun 2005. doi:10.1093/ajcn/81.6.1436. PMID 15941899.
- "Transcriptome analysis of human gastric cancer". Mammalian Genome 16 (12): 942–54. Dec 2005. doi:10.1007/s00335-005-0075-2. PMID 16341674.
- "Identification of N-linked glycoproteins in human saliva by glycoprotein capture and mass spectrometry". Journal of Proteome Research 5 (6): 1493–503. Jun 2006. doi:10.1021/pr050492k. PMID 16740002.
- "Variation at the NFATC2 locus increases the risk of thiazolidinedione-induced edema in the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) study". Diabetes Care 33 (10): 2250–3. Oct 2010. doi:10.2337/dc10-0452. PMID 20628086.
![]() | Original source: https://en.wikipedia.org/wiki/Haptocorrin.
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