Gastric intrinsic factor

Also, the outcome covers a large spectrum. Autoantibodies can specifically block an important protein (such as the gastric intrinsic factor required for the uptake of orally taken vitamin B12), or the receptor for —> acetylcholine (as in myasthenia gravis), but also can... 

The treatment of an autoimmune disease very much depends on the nature of the clinical outcome it causes. Although the formation of autoantibodies causes the inactivation of the gastric intrinsic factor, the subsequent shortage of vitamin B12 can be easily overcome by supplying it via an parenteral route. Lifelong immunosuppression (with all its side effects) thus is inappropriate. When, however, as in sympathetic ophtalmia, after damage of the first eye the second eye is endangered, an even drastic immunosuppression is mandatory. 

Shaw, S., Herbert, V., Colman, N. and Jayatilleke, E. (1990). Effect of ethanol-generated free radicals on gastric intrinsic factor and glutathione. Alcohol 7, 153-157. 

There are several steps in the absorption of vitamin B. In the stomach and lumen of the small intestine it is hydrolysed from its (peptide) links with the proteins of which it is a component. It then attaches to gastric intrinsic factor, which is a glycoprotein of molecular mass about 50 000 kDa, to form a complex. This protects the vitamin from being damaged by acid in the stomach. The complex is carried into the ileum, where it binds to a receptor on the surface of the absorptive cells and is released from the intrinsic factor within the absorptive cell, hi the portal venous blood, it is transported to the liver bound to the vitamin B 12-binding protein, which also protects the vitamin. 

The main causes for vitamin B12 deficiency are impaired absorption due to a lack of gastric intrinsic factor (e.g. pernicious anemia), ileal abnormalities, or it can be the result of a strictly vegetarian diet. 

Severe cyanocobalamin (vitamin B12) deficiency results in pernicious anemia that is characterized by megaloblastic anemia and neuropathies. The symptoms of this deficiency can be masked by high intake of folate. Vitamin B12 is recycled by an effective enterohep-atic circulation and thus has a very long half-hfe. Absorption of vitamin B12 from the gastrointestinal tract requires the presence of gastric intrinsic factor. This factor binds to the vitamin, forming a complex that... 

This vitamin is not synthesized in animals, but rather it results from the bacterial or fungal fermentation in the rumen, after which it is absorbed and concentrated during metabolism. Among the known vitamins, this exclusive microbial synthesis is of great interest. One of the major results of vitamin Bn deficiency is pernicious anemia. This disease, however, usually does not result from a dietary deficiency of the vitamin, but rather by an absence of a glycoprotein ( gastric intrinsic factor ) in the gastric juices that facilitates absorption of the vitamin in the intestine. Control of the diseases hence is either by injection of Bn or by oral administration of the intrinsic factor, with or without the vitamin injection. 

DEFICIENCY Pernicious anemia. Conceivably, one could get Bi2 deficiency on a purely vegetarian diet, but this is rare. Deficiency is more likely with diseases of the intestine that impede absorption (e.g., tropical sprue, regional enteritis). The tapeworm Diphyllobothrium latum may deplete Bi2 stores. A deficiency of gastric intrinsic factor (a glycoprotein) may result in Bj2 deficiency, as intrinsic factor is important in facilitating Bj2 absorption in the bowel. Intrinsic factor deficiency may occur following gastrectomy or as an entity in itself, in pernicious anemia. Intrinsic factor deficiency sometimes results from an autoimmune disease. 

A9a. Ardeman, S., and Chanarin, I., A method for the assay of human gastric intrinsic factor and for the detection and titration of antibodies against intrinsic factor. Lancet 2, 1350-1354 (1963). 

C6. Castle, W. B., Development of knowledge concerning the gastric intrinsic factor and its relation to pernicious anemia. New Engl. J. Med. 249, 603-614 (1953). 

Cobalamin (Bi 2) Pernicious anemia, glossitis, spinal cord degeneration, peripheral neuropathy Serum Bi 2 Decreased absorption in the elderly, distal ileal resection, loss of gastric intrinsic factor... 

Jerzy Glass, G. Gastric intrinsic factor and its function in the metabolism of vitamin B12- Physiol. Rev. 43, 529-849 (1963)... 

Hoedemaker PJ, Abels J, Wachters JJ, et al. Investigations about the site of production of Castle s gastric intrinsic factor. Lab Invest 13 1394-1399, 1964. 

To our knowledge, all commercially available assays today employ intrinsic factor as the binding protein. The challenge with this is that the most commonly used source of intrinsic factor is the porcine stomach, a source that contains a substantial amount of haptocorrin in addition to intrinsic factor. Because of this, care is needed to remove haptocorrin prior to using porcine gastric intrinsic factor. It seems obvious that, in order to standardize assays for cobalamin across the analytical platforms, the use of recombinant intrinsic factor is relevant. Recombinant human intrinsic factor is available and has... 

Vitamin B12 is not abundantly contained in foods and is especially scarce in plant foods. To absorb this rare vitamin efficiently, the human body has an ingenious system. Dietary vitamin B12 binds to gastric intrinsic factor and is transported via a receptor present in the small intestine to the epithelial cells here it and is taken up in the circulation where it binds to transcobalamin II. The complex of transcobalamin II and B12 is then transported to the eells of target organs by endocytosis via a receptor expressed in the membrane of the cells. 

There have been not been any reports indicating that renal dysfunction affects the intake and absorption of vitamin B12. However, renal failure is associated with gastric epithelial cell dysfunction, which may reduce the release of gastric intrinsic factor. Moreover, decreased renal function may induce anorexia, which results in a reduction in food intake (Kopple et al. 1999). 

In man, as in carnivorous and omnivorous animals, supplies of vitamin Bn are derived chiefly from animal foods. Absorption of ingested vitamin B12 is facilitated by the action of gastric intrinsic factor. 

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