In most countries, intramuscular injections of vitamin B 12 are used to treat pernicious anemia.
Mutations in the GIF gene are responsible for a rare inheritable disease called intrinsic factor deficiency which results in malabsorption of vitamin B 12. 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. Pancreatic exocrine insufficiency can interfere with normal dissociation of vitamin B 12 from its binding proteins in the small intestine, preventing its absorption via the intrinsic factor complex. Atrophic gastritis can also cause intrinsic factor deficiency and anemia through damage to the parietal cells of the stomach wall. 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 B 12, and subsequent megaloblastic anemia. The limited amount of normal human gastric intrinsic factor limits normal efficient absorption of B 12 to about 2 μg per meal, a nominally adequate intake of B 12. 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 site of formation of the intrinsic factor varies in different species. 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 optimum pH for its action is approximately 7. The intrinsic factor is secreted by the stomach, and so is present in the gastric juice as well as in the gastric mucous membrane. Inside the cells, vitamin B 12 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. This new complex is then absorbed by the epithelial cells ( enterocytes) of the ileum. In the less acidic environment of the small intestine, pancreatic enzymes digest the glycoprotein carrier and vitamin B 12 can then bind to intrinsic factor. Vitamin B 12 is acid-sensitive and in binding to transcobalamin I it can safely pass through the acidic stomach to the duodenum. Haptocorrin (also known as HC, R protein, and transcobalamin I, TCN1) is another glycoprotein secreted by the salivary glands which binds to vitamin B 12. In humans, the gastric intrinsic factor protein is encoded by the GIF gene. It is necessary for the absorption of vitamin B 12 later on in the distal ileum of the small intestine. Intrinsic factor ( IF), also known as gastric intrinsic factor ( GIF), is a glycoprotein produced by the parietal cells (in humans) or chief cells (in rodents) of the stomach.
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