gastric intrinsic factor

WordNet

1. be a contributing factor; "make things factor into a companys profitability"
2. any of the numbers (or symbols) that form a product when multiplied together
3. an independent variable in statistics
4. anything that contributes causally to a result; "a number of factors determined the outcome"
5. consider as relevant when making a decision; "You must factor in the recent developments" (同)factor in, factor out
6. resolve into factors; "a quantum computer can factor the number 15" (同)factor in, factor out
7. an event known to have happened or something known to have existed; "your fears have no basis in fact"; "how much of the story is fact and how much fiction is hard to tell"
8. a concept whose truth can be proved; "scientific hypotheses are not facts"
9. a piece of information about circumstances that exist or events that have occurred; "first you must collect all the facts of the case"
10. a statement or assertion of verified information about something that is the case or has happened; "he supported his argument with an impressive array of facts"
11. situated within or belonging solely to the organ or body part on which it acts; "intrinsic muscles"
12. belonging to a thing by its very nature; "form was treated as something intrinsic, as the very essence of the thing"- John Dewey (同)intrinsical
13. relating to or involving the stomach; "gastric ulcer" (同)stomachic, stomachal

PrepTutorEJDIC

1. (…の)『要因』,(…を生み出す)要素《+『in』+『名』(do『ing』)》 / 囲数,約数 / 代理人,《おもに英》仲買人 / =factorize
2. 〈C〉『事実』,実際にある(あった)事 / 〈U〉真相,真実(truth) / 《the~》(法律用語で)犯行
3. (価値・質などが)本質的な,本来備わった
4. 胃の,胃に発生する

Wikipedia preview

出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2014/12/20 03:37:15」(JST)

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Gastric intrinsic factor (vitamin B synthesis)
Rendering based on PDB 2CKT
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 2PMV, 3KQ4
Identifiers
Symbols	GIF ; IF; IFMH; INF; TCN3
External IDs	OMIM: 609342 MGI: 1202394 HomoloGene: 3773 GeneCards: GIF Gene
Gene ontology Molecular function • cobalamin binding Cellular component • extracellular space • endosome • microvillus • apical plasma membrane Biological process • cobalt ion transport • cobalamin metabolic process • cobalamin transport Sources: Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	2694	14603
Ensembl	ENSG00000134812	ENSMUSG00000024682
UniProt	P27352	P52787
RefSeq (mRNA)	NM_005142	NM_008118
RefSeq (protein)	NP_005133	NP_032144
Location (UCSC)	Chr 11: 59.6 – 59.61 Mb	Chr 19: 11.75 – 11.76 Mb
PubMed search	[1]	[2]

Intrinsic factor (IF), also known as gastric intrinsic factor (GIF), is a glycoprotein produced by the parietal cells of the stomach. It is necessary for the absorption of vitamin B₁₂ (cobalamin) later on in the small intestine. In humans, the gastric intrinsic factor protein is encoded by the GIF gene.

Haptocorrin (also known as HC, R protein, and transcobalamin I, TCN1), is a glycoprotein secreted by the salivary glands which binds to vitamin B₁₂. Vitamin B₁₂ is acid sensitive and in binding to transcobalamin I it can safely pass through the acidic stomach to the duodenum. Here in the less acidic environment of the small intestine, pancreatic enzymes digest the glycoprotein carrier and vitaminB₁₂ can then bind to intrinsic factor. This new complex is then absorbed by the epithelial cells (enterocytes) of the ileum. Inside the cells, B₁₂ dissociates once again and binds to another protein, transcobalamin II (TCN2). The new complex can then exit the epithelial cells to be carried to the liver.

Site of secretion

The intrinsic factor is secreted by the stomach. It is present in the gastric juice as well as in the gastric mucous membrane. The optimum pH for its action is 7 and it is inactivated at temperatures above 45 °C. It does not necessarily run parallel with the amount of HCl or pepsin in the gastric juice. So in some cases, the intrinsic factor may be present even if there is no HCl or pepsin or vice versa. The site of formation of the intrinsic factor varies in different species. In pigs it is obtained from the pylorus and beginning of the duodenum. In human beings it is present in the fundus and body of the stomach.

Clinical significance

In pernicious anemia, which is usually an autoimmune disease, autoantibodies directed against intrinsic factor or parietal cells themselves lead to an intrinsic factor deficiency, malabsorption of vitamin B₁₂, and subsequent megaloblastic anemia. Atrophic gastritis can also cause intrinsic factor deficiency and anemia through damage to the parietal cells of the stomach wall. Pancreatic exocrine insufficiency can interfere with normal dissociation of vitamin B₁₂ from its binding proteins in the small intestine, preventing its absorption via the intrinsic factor complex.

Other risk factors contributing to pernicious anemia are anything that damages or removes a portion of the stomach's parietal cells, including bariatric surgery, gastric tumors, gastric ulcers, and excessive consumption of alcohol.

Treatment

Patients experiencing an insufficiency in their intrinsic factor levels cannot benefit from a low dose oral vitamin B₁₂ supplement, because it will not absorb through the wall of the small intestine. Historically, the disease was thought untreatable before the discovery that it could be managed with daily uptake of 300 g raw liver pulp (Nobel Prize in Physiology or Medicine 1934 to Whipple, Minot & Murphy). Unlike other water-soluble vitamins, vitamin B₁₂ is stored in the liver. The high dose of vitamin B₁₂ thus ingested allows enough of it to be taken up passively. As more and more potent liver extracts became available this repugnant treatment became unnecessary, improving the life quality of the patients. Today, synthetic vitamin B₁₂ can be injected monthly, thus bypassing the digestive tract altogether.

References

Further reading

• Howard TA, Misra DN, Grove M, et al. (1996). "Human gastric intrinsic factor expression is not restricted to parietal cells". J. Anat. 189 (Pt 2): 303–13. PMC 1167747. PMID 8886952. 
• Kozyraki R, Kristiansen M, Silahtaroglu A, et al. (1998). "The human intrinsic factor-vitamin B12 receptor, cubilin: molecular characterization and chromosomal mapping of the gene to 10p within the autosomal recessive megaloblastic anemia (MGA1) region". Blood 91 (10): 3593–600. PMID 9572993. 
• Wahlstedt V, Gräsbeck R (1985). "Cobalamin-binding proteins in human urine: identification and quantitation". J. Lab. Clin. Med. 106 (4): 439–46. PMID 4045300. 
• Remacha AF, Del Río E, Sardà MP, et al. (2008). "Role of (Glu --> Arg, Q5R) mutation of the intrinsic factor in pernicious anemia and other causes of low vitamin B12". Ann. Hematol. 87 (7): 599–600. doi:10.1007/s00277-008-0465-0. PMID 18338170. 
• Ament AE, Li Z, Sturm AC, et al. (2009). "Juvenile cobalamin deficiency in individuals of African ancestry is caused by a founder mutation in the intrinsic factor gene GIF". Br. J. Haematol. 144 (4): 622–4. doi:10.1111/j.1365-2141.2008.07496.x. PMC 2636683. PMID 19036097. 
• Mathews FS, Gordon MM, Chen Z, et al. (2007). "Crystal structure of human intrinsic factor: cobalamin complex at 2.6-A resolution". Proc. Natl. Acad. Sci. U.S.A. 104 (44): 17311–6. doi:10.1073/pnas.0703228104. PMC 2077253. PMID 17954916. 
• Fedosov SN, Fedosova NU, Berglund L, et al. (2005). "Composite organization of the cobalamin binding and cubilin recognition sites of intrinsic factor". Biochemistry 44 (9): 3604–14. doi:10.1021/bi047936v. PMID 15736970. 
• Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The Status, Quality, and Expansion of the NIH Full-Length cDNA Project: The Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334. 
• Tanner SM, Li Z, Perko JD, et al. (2005). "Hereditary juvenile cobalamin deficiency caused by mutations in the intrinsic factor gene". Proc. Natl. Acad. Sci. U.S.A. 102 (11): 4130–3. doi:10.1073/pnas.0500517102. PMC 554821. PMID 15738392. 
• Yassin F, Rothenberg SP, Rao S, et al. (2004). "Identification of a 4-base deletion in the gene in inherited intrinsic factor deficiency". Blood 103 (4): 1515–7. doi:10.1182/blood-2003-07-2239. PMID 14576042. 
• Gordon MM, Brada N, Remacha A, et al. (2004). "A genetic polymorphism in the coding region of the gastric intrinsic factor gene (GIF) is associated with congenital intrinsic factor deficiency". Hum. Mutat. 23 (1): 85–91. doi:10.1002/humu.10297. PMID 14695536. 
• Strausberg RL, Feingold EA, Grouse LH, et al. (2002). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932. 
• Andersen CB, Madsen M, Storm T, et al. (2010). "Structural basis for receptor recognition of vitamin-B(12)-intrinsic factor complexes". Nature 464 (7287): 445–8. doi:10.1038/nature08874. PMID 20237569. 
• Katz M, Lee SK, Cooper BA (1972). "Vitamin B 12 malabsorption due to a biologically inert intrinsic factor". N. Engl. J. Med. 287 (9): 425–9. doi:10.1056/NEJM197208312870902. PMID 5044916. 
• Yazaki Y, Chow G, Mattie M (November 2006). "A single-center, double-blinded, randomized controlled study to evaluate the relative efficacy of sublingual and oral vitamin B-complex administration in reducing total serum homocysteine levels". J Altern Complement Med 12 (9): 881–5. doi:10.1089/acm.2006.12.881. PMID 17109579. 

External links

• Intrinsic factor at the US National Library of Medicine Medical Subject Headings (MeSH)
• MedlinePlus Encyclopedia 002381
• Overview at colostate.edu

UpToDate Contents

全文を閲覧するには購読必要です。 To read the full text you will need to subscribe.

• 1. ビタミンB12および葉酸欠乏症の病因および臨床症状 etiology and clinical manifestations of vitamin b12 and folate deficiency
• 2. Bariatric procedures for the management of severe obesity: Descriptions
• 3. 大型の胃粘膜ひだ：過形成および非過形成性の胃疾患 large gastric folds hyperplastic and nonhyperplastic gastropathies
• 4. 肥満手術後の生殖能力および妊娠 fertility and pregnancy after bariatric surgery
• 5. 化生（慢性）萎縮性胃炎 metaplastic chronic atrophic gastritis

English Journal

• Intrinsic resistance triggered under acid loading within normal esophageal epithelial cells: NHE1- and ROS-mediated survival.

• Park SY1, Lee YJ, Cho EJ, Shin CY, Sohn UD.
• Journal of cellular physiology.J Cell Physiol.2015 Jul;230(7):1503-14. doi: 10.1002/jcp.24896.
• The transition to a pathological phenotype such as Barrett's esophagus occurs via induction of resistance upon repeated contact with gastric refluxate in esophagus. This study examined the molecular changes within normal esophageal epithelial cells (EECs) under short-term acid loading and the role o
• PMID 25522216

• Distal renal tubular acidosis with multiorgan autoimmunity: a case report.

• van den Wildenberg MJ1, Hoorn EJ2, Mohebbi N3, Wagner CA4, Woittiez AJ5, de Vries PA5, Laverman GD5.
• American journal of kidney diseases : the official journal of the National Kidney Foundation.Am J Kidney Dis.2015 Apr;65(4):607-10. doi: 10.1053/j.ajkd.2014.09.026. Epub 2014 Dec 18.
• A 61-year-old woman with a history of pernicious anemia presented with progressive muscle weakness and dysarthria. Hypokalemic paralysis (serum potassium, 1.4 mEq/L) due to distal renal tubular acidosis (dRTA) was diagnosed. After excluding several possible causes, dRTA was considered autoimmune. Ho
• PMID 25533600

Japanese Journal

• 経静脈栄養離脱後4年でビタミンB_<12>欠乏性巨赤芽球性貧血を発症した短小腸の1例

• 黒岩 実,西 明,山本 英輝,大竹 紗弥香,畑中 政博,鈴木 則夫
• 日本小児外科学会雑誌 46(5), 857-861, 2010-08-20
• 患児は7歳2月の男児.日齢1で回腸閉鎖,胎便性腹膜炎のため開腹され,空腸結腸吻合が行われた(残存空腸70cm).2歳8月で経静脈栄養より離脱したが,6歳過ぎから原因不明の高ビリルビン血症がみられ,その後全身倦怠感や運動時の息切れが出現した.血液検査で貧血(大球性高色素性)を認め,血中葉酸は正常だがビタミンB_<12>(VB_<12>)は71pg/mlと低値で,抗内因子抗体お …
• NAID 110007682256

Related Links

• gastric intrinsic factor - definition of gastric intrinsic factor by ...

gastric intrinsic factor (GIF), n a substance secreted by the gastric mucosa that is essential for the intestinal absorption of vitamin B 12; also known as ... Disclaimer All content on this website, including dictionary, thesaurus ...

• Gastric intrinsic factor. - ResearchGate

Publication » Gastric intrinsic factor.. Article Gastric intrinsic factor. I Chanarin Gut (Impact Factor: 13.32). 09/1968; 9(4):373-5. DOI: 10.1136/gut.9.4.373 Source: PubMed 0 Bookmarks · 47 Views Citations (27) Cited In (8) , ...

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★リンクテーブル★

リンク元	「内因子」
関連記事	「intrinsic」「fact」「factor」「gastric」

「内因子」

　　[★]

英

intrinsic factor IF

同

胃内因子 gastric intrinsic factor、キャッスル内因子 Castle intrinsic factor、抗悪性貧血因子 antipernicious anemia factor, anti-pernicious anemia factor

関

悪性貧血

• 胃体部に存在する壁細胞から分泌される。
• 悪性貧血有効成分。

「intrinsic」

　　[★]

• adj.

• 内因性の、内在性の、固有の、内在的な、内因的な

関

endemic、endogeneous、endogenous、endogenously、inherent、inherently、intrinsically、proper

　 　 　

「fact」

　　[★]

• n.

• 事実、現状、実際、実態

関

actual、actually、in fact、in practice、indeed、practically

　 　 　 　 　

「factor」

　　[★]

• n.

• 因子、要因、要素、ファクター

関

element、elementary、factorial、parameter

　 　 　 　 　 　 　

「gastric」

　　[★]

• adj.

• 胃の

関

gastro、stomach、ventriculi、ventriculus