Intrinsic factor is a glycoprotein secreted by parietal (humans) or chief (rodents) cells of the gastric mucosa. In humans, it has an important role in the absorption of vitamin B12 (cobalamin) in the intestine, and failure to produce or utilize intrinsic factor results in the condition pernicious anemia.
Dietary vitamin B12 is released from ingested proteins in the stomach through the action of pepsin and acid. It is rapidly bound by one of two vitamin B12-binding proteins that are present in gastric juice; at acid pH, these binding proteins have a greater affinity for the vitamin than does intrinsic factor. In the small intestine, pancreatic proteases digest the binding proteins, releasing vitamin B12 which then becomes bound to intrinsic factor. Finally, there are receptors for intrinsic factor on the ileal mucosa which bind the complex, allowing vitamin B12 to be absorbed into portal blood.
In all mammals, vitamin B12 is necessary for maturation of erythrocytes, and a deficiency of this vitamin leads to development of anemia. Since efficient absorption of vitamin B12 in humans depends on intrinsic factor, diseases which decrease the secretion of intrinsic factor (e.g. atrophic gastritis), interfere with cleavage of the binding proteins (e.g. pancreatic exocrine insufficiency) or decrease binding and absorption of the intrinsic factor-vitamin B12 complex (e.g. ileal disease or resection) can result in this type of anemia. In cattle and sheep, deficiency in cobalt, which is a necessary component of vitamin B12, can result in anemia among other signs of disease.