Intrinsic Factor

Gastric intrinsic factor (IF) can be defined as a substance required for the absorption of vitamin B12 (cyanocobalamin, CNCb1), which is essential for the formation of red blood cells. Cyanocoba-lamin is a precursor for methylcobalamin, a cofac-tor for the enzyme methionine synthase, and 5' deoxyadenosylcobolamin, a cofactor for methyl-manonyl CoA mutase. In the absence of IF,

CNCbl fails to be absorbed, erythrocyte production is defective, and pernicious anemia results. The most detrimental effect of gastric mucosal atrophy, which can result from long-term H. pylori infection, is the loss of intrinsic factor. Two other CNCbl binders exist in the body that are distinct from IF; these are haptocorrin (Hc), the ubiquitous binder, and transcobalamin II (TCII), the plasma binder that transports CNCbl from the terminal ileum.

Dietary CNCbl is always bound to proteins and is released by cooking and pepsin digestion. In gastric juice, free CNCbl is faced with both gastric IF and Hc mainly derived from saliva. At pH 2.0 CNCbl affinity for Hc is 50 times higher than for IF; therefore, free CNCbl binds to Hc in the stomach. However, in the small intestine trypsin degrades He and CNCbl is bound by IF. The CNCbl-IF complex is absorbed in the terminal ileum after interaction with a receptor (IFRC) specific to IF-CNCbl.

The gene for IF is found at chromosomal location 11q13. Purified IF is a glycoprotein of approximately 57 kD. Its protein component varies between 341 and 351 residues and the carbohydrate moiety, consisting of 30-37 residues, 49-68% hexoses, 27-37% hexosamines and 13-18% sialic acid, constitutes 9.2-15% of the molecule (6.1-6.6kD). The sugar chains are either O-glycosidically or N-lacto-saminically linked. In vitro transcription/translation studies have shown that removing 12% of the C-terminus of the molecule results in all CNCbl binding activity being lost; the receptor binding region is at residues 25-44.

IF is classically described as being secreted by stomach fundus and body parietal cells; however, the use of immunocytochemistry, electron microscopy, and in situ hybridization has shown that it is also found in a subset of chief cells, enteroendo-crine cells, G cells, and in secretory ducts of the salivary glands. This may explain the fact that control of IF secretion is apparently multifactorial in common with other gastric juice components and can be activated by gastrin, histamine, acetylcholine, and cholecystokinin. IF secretion in man varies between 50 and 100nmoll~1 which far exceeds the daily requirement.

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