Intrinsic Factor

It is necessary for the absorption of vitamin B₁₂ later on in the distal ileum of the small intestine. In humans, the gastric intrinsic factor protein is encoded by the CBLIF gene. Haptocorrin (transcobalamin I) is another glycoprotein secreted by the salivary 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.

CBLIF
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2PMV, 3KQ4
Identifiers
Aliases	CBLIF, IF, IFMH, INF, TCN3, gastric intrinsic factor, intrinsic factor, Intrinsic factor , IF, cobalamin binding intrinsic factor, GIF
External IDs	OMIM: 609342 MGI: 1202394 HomoloGene: 3773 GeneCards: CBLIF
Gene location (Human) Chr. Chromosome 11 (human) Band 11q12.1 Start 59,829,273 bp End 59,845,499 bp
Gene location (Mouse) Chr. Chromosome 19 (mouse) Band 19|19 A Start 11,724,918 bp End 11,740,811 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in cardia pylorus body of stomach fundus pancreatic ductal cell right lung canal of the cervix rectum blood optic nerve Top expressed in epithelium of stomach pyloric antrum mucous cell of stomach left lung lobe quadriceps femoris muscle superior colliculus duodenum esophagus jejunum exocrine gland More reference expression data BioGPS n/a
Gene ontology Molecular function cobalamin binding Cellular component extracellular region microvillus endosome lysosomal lumen apical plasma membrane extracellular space Biological process cobalt ion transport ion transport cobalamin transport cobalamin metabolic process 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: 59.83 – 59.85 Mb Chr 19: 11.72 – 11.74 Mb PubMed search
Wikidata
View/Edit Human View/Edit Mouse

In the less acidic environment of the small intestine, pancreatic enzymes digest the glycoprotein carrier and vitamin B₁₂ can then bind to intrinsic factor. This new complex is then absorbed by the epithelial cells (enterocytes) of the ileum. 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.

Intrinsic factor is secreted by parietal cells within the stomach, and so is present in the gastric juice as well as in the gastric mucous membrane. The optimum pH for its action is approximately 7. Its concentration does not correlate with the amount of HCl or pepsin in the gastric juice, e.g., intrinsic factor may be present even when pepsin is largely absent. 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.

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.

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.^{[citation needed]}

Mutations in the GIF gene are responsible for a rare inheritable disease called intrinsic factor deficiency which results in malabsorption of vitamin B₁₂.

Treatment

In most countries, intramuscular injections of vitamin B₁₂ are used to treat pernicious anemia. Orally administered vitamin B₁₂ is absorbed without intrinsic factor, but at levels of less than one percent than if intrinsic factor is present. Despite the low amounts absorbed, oral vitamin B₁₂ therapy is effective at reducing symptoms of pernicious anemia.

Vitamin B₁₂ can also be given sublingually, but there is no evidence that this route of administration is superior to the oral route, and only Canada and Sweden routinely prescribe this route of administration.

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 because Haptocorrin (transcobalamin I) binds to vitamin B₁₂, and Vitamin B₁₂ is acid-sensitive, when vitamin B₁₂ binds to Haptocorrin it can safely pass through the acidic stomach to the duodenum, given time in the mouth.

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