Intrinsic factor (IF), also known ascobalamin binding intrinsic factor,[5] orgastric intrinsic factor (GIF), is aglycoprotein produced by theparietal cells (in humans) orchief cells (in rodents) of thestomach. It is necessary for the absorption ofvitamin B12 later on in the distalileum of thesmall intestine.[6] In humans, the gastric intrinsic factorprotein is encoded by theCBLIFgene.[5]Haptocorrin (transcobalamin I) is another glycoprotein secreted by thesalivary glands which binds to vitamin B12. Vitamin B12 is acid-sensitive and in binding to haptocorrin it can safely pass through the acidic stomach to the duodenum.[7]
In the less acidic environment of thesmall intestine, pancreatic enzymes digest the glycoprotein carrier and vitamin B12 can then bind to intrinsic factor.[7] This new complex is then absorbed by the epithelial cells (enterocytes) of theileum.[7] Inside the cells, vitamin B12 dissociates once again and binds to another protein,transcobalamin II; the new complex can then exit the epithelial cells to be carried to the liver.[8]
Intrinsic factor is secreted byparietal cells within the stomach, and so is present in the gastric juice as well as in thegastric mucous membrane.[9] The optimum pH for its action is approximately 7.[10] Its concentration does not correlate with the amount ofHCl orpepsin in the gastric juice, e.g., intrinsic factor may be present even when pepsin is largely absent.[11] The site of formation of the intrinsic factor varies in different species. In pigs it is obtained from thepylorus and beginning of theduodenum;[12] in human beings it is present in thefundus and body of thestomach.[13]
The limited amount of normal human gastric intrinsic factor limits normal efficient absorption of B12 to about 2 μg per meal, a nominally adequate intake of B12.[14]
Inpernicious anemia, which is usually anautoimmune disease,autoantibodies directed against intrinsic factor or parietal cells themselves lead to an intrinsic factor deficiency,malabsorption of vitamin B12, and subsequentmegaloblastic anemia.[15]Atrophic gastritis can also cause intrinsic factor deficiency and anemia through damage to the parietal cells of the stomach wall.[16]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.[17] Other risk factors contributing to pernicious anemia are anything that damages or removes a portion of the stomach's parietal cells, includingbariatric surgery, gastric tumors, gastric ulcers, and excessive consumption of alcohol.[citation needed]
Mutations in theGIF gene are responsible for a rare inheritable disease calledintrinsic factor deficiency[18] which results in malabsorption of vitamin B12.[19]
In most countries,intramuscular injections of vitamin B12 are used to treatpernicious anemia.[20] Orally administered vitamin B12 is absorbed without intrinsic factor, but at levels of less than one percent than if intrinsic factor is present.[21] There are not enough studies on whether pills are as effective in improving or eliminating symptoms as parenteral treatment.[22]
Vitamin B12 can also be givensublingually, but there is no evidence that this route of administration is superior to the oral route,[23] and only Canada and Sweden routinely prescribe this route of administration.[20]
Because vitamin B12 absorption is a multistep process that involves the stomach, pancreas and small intestine, and is mediated by two carriers:Haptocorrin and intrinsic factor, and becauseHaptocorrin (transcobalamin I) binds to vitamin B12, and Vitamin B12 is acid-sensitive, when vitamin B12 binds toHaptocorrin it can safely pass through the acidic stomach to the duodenum, given time in the mouth.[7]
^Alpers DH, Russell-Jones G (May 2013). "Gastric intrinsic factor: the gastric and small intestinal stages of cobalamin absorption. A personal journey". (review).Biochimie.95 (5):989–994.doi:10.1016/j.biochi.2012.12.006.PMID23274574.
^Sharma K (2016)."Gastrointestinal System". In Talwar G, Hasnain SE, Sarin SK (eds.).Textbook Of Biochemistry, Biotechnology, Allied And Molecular Medicine. (secondary) (4th ed.). PHI Learning Private Limited. p. 632.ISBN978-81-203-5125-7.
^Poliner IJ, Spiro HM, Pask BA, Trocchio N (Feb 1958). "The independent secretion of acid, pepsin, and intrinsic factor by the human stomach". (primary).Gastroenterology.34 (2):196–209.doi:10.1016/S0016-5085(58)80102-X.PMID13512593.
^Heatley NG, Florey H, Turnbull A, Jennings MA, Watson GM, Wakisaka G, et al. (Sep 1954). "Intrinsic factor in the pyloric and duodenal secretions of the pig". (primary).Lancet.267 (6838). London, England:578–580.doi:10.1016/S0140-6736(54)90355-4.PMID13193076.
^Watanabe F (Nov 2007). "Vitamin B12 sources and bioavailability". (review).Experimental Biology and Medicine.232 (10). Maywood, N.J.:1266–1274.doi:10.3181/0703-MR-67.PMID17959839.S2CID14732788.
^Osborne D, Sobczyńska-Malefora A (Sep 2015). "Autoimmune mechanisms in pernicious anaemia & thyroid disease". (review).Autoimmunity Reviews.14 (9):763–768.doi:10.1016/j.autrev.2015.04.011.PMID25936607.
^Neumann WL, Coss E, Rugge M, Genta RM (Sep 2013). "Autoimmune atrophic gastritis--pathogenesis, pathology and management". (review).Nature Reviews. Gastroenterology & Hepatology.10 (9):529–541.doi:10.1038/nrgastro.2013.101.PMID23774773.S2CID205487577.
^Guéant JL, Champigneulle B, Gaucher P, Nicolas JP (Sep 1990). "Malabsorption of vitamin B12 in pancreatic insufficiency of the adult and of the child". (review).Pancreas.5 (5):559–567.doi:10.1097/00006676-199009000-00011.PMID2235967.S2CID9077477.
Christensen EI, Nielsen R, Birn H (Feb 2013). "From bowel to kidneys: the role of cubilin in physiology and disease". (review).Nephrology, Dialysis, Transplantation.28 (2):274–281.doi:10.1093/ndt/gfs565.PMID23291372.
