Intrinsic factor

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Gastric intrinsic factor (vitamin B synthesis)
Protein GIF PDB 2CKT.png
Rendering based on PDB 2CKT
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols GIF ; IF; IFMH; INF; TCN3
External IDs OMIM609342 MGI1202394 HomoloGene3773 GeneCards: GIF Gene
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.[1] In humans, the gastric intrinsic factor protein is encoded by the GIF gene.[2]

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[edit]

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[edit]

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[edit]

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[edit]

  1. ^ Pocock, G and Richards, C (2006). Human Physiology:The Basis of Medicine (3rd ed.). Oxford University Press. p. 230. ISBN 978-019-856878-0. 
  2. ^ Hewitt JE, Gordon MM, Taggart RT, Mohandas TK, Alpers DH (June 1991). "Human gastric intrinsic factor: characterization of cDNA and genomic clones and localization to human chromosome 11". Genomics 10 (2): 432–40. doi:10.1016/0888-7543(91)90329-D. PMID 2071148. 

Further reading[edit]

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