Intrinsic factor

protein
Name = Gastric intrinsic factor
caption =


width =
HGNCid = 4268
Symbol = GIF
AltSymbols =
EntrezGene = 2694
OMIM = 609342
RefSeq = NM_005142
UniProt = P27352
PDB =
ECnumber =
Chromosome = 11
Arm = q
Band = 13
LocusSupplementaryData =

Intrinsic factor is a glycoprotein produced by the parietal cells of the stomach. It is necessary for the absorption of vitamin Bssub|12 later on in the terminal ileum.

Upon entry into the stomach, vitamin Bssub|12 becomes bound to one of two Bssub|12 binding proteins present in gastric juice. In the less acidic environment of the small intestine, these proteins dissociate from the vitamin, enabling it to bind to intrinsic factor and enter the portal circulation through a receptor in the ileal mucosa specific for the Bssub|12-intrinsic factor complex.

ite of Secretion

The intrinsic factor, as suggested by Castle, is an enzyme like unidentified substance secreted by the stomach. It is present in he 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^oC. 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, an autoimmune disease, autoantibodies directed against intrinsic factor or parietal cells themselves lead to an intrinsic factor deficiency, malabsorption of vitamin Bssub|12, 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 Bssub|12 from its binding proteins in the small intestine, preventing its absorption via the intrinsic factor complex.

Bariatric surgery is a known risk factor in the development of pernicious anemia. Other risk factors contributing to this condition are stomach 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 B-12 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 regular injections of vitamin B-12, thus bypassing the digestive tract. More recently, Swedish researchers discovered that sufficiently large doses of B-12 can also be absorbed sublingually, so injections are necessary only for those unable to take pills by sublingual administration.

External links

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* [http://www.vivo.colostate.edu/hbooks/pathphys/digestion/stomach/intrinsic_factor.html Overview at colostate.edu]

References

Yuka Yazaki, Gigi Chow, Mark Mattie. (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." Journal of Alternative and Complementary Medicine. doi:10.1089/acm.2006.12.881.

Human Physiology: For Preclinical Medical and Degree Courses in Physiology by Chandi Charan Chatterjee; Published by A.K. Chatterjee, 1985. Pg-438.