Castle’s intrinsic factor

One aspect of the biological activity of the glandular mucoprotein fraction was its relationship to Castle s intrinsic factor (GIO, G37). A daily dose of 50-100 mg of this material, when given to pernicious anemia patients with small oral doses of vitamin Bis, brought about a striking hematopoietic response. This activity was due, as we now know, to the content of the proteolytic degradation product of intrinsic factor (G12, G14, G18, G20, S22). 

Osgood demonstrated that pernicious anemia serum delays maturation of megaloblastic bone marrow (see LI). The work of Callender and Lajtha (see G20) points out that addition of normal gastric juice potentiates the effect of vitamin B12 in counteracting this maturation-delaying effect of pernicious anemia serum. A B12 binder separated from normal gastric juice by electrophoresis or ammonium sulfate precipitation was also shown to enhance the B12 effect on maturation of the erythro-blasts, when added to bone marrow (P2, P3). The relation of this maturation-promoting factor to Castle s intrinsic factor is not clearly defined (see G20). 

TIO. Taylor, K. B., An antibody to Castle s intrinsic factor. Haematol. Latina (Milan) 2, 181-186 (1959). 

Castle s intrinsic factor a substance produced by the stomach which combines with the extrinsic factor (vitamin B12) in food to yield an antianemic principle, its lack is believed to cause pernicious anemia cation exchange capacity a measure of the capability of a substance or a (solid) material to bind cations in a reversible marmer CCP see CCPAES... 

Ungley CC, Moffett R. Observations on Castle s intrinsic factor in pernicious anaemia. Lancet 1 1232-1235, 1936. 

Fisher JM, Taylor KB. The intracellular localization of Castle s intrinsic factor by immunofluorescent technique using autoantibodies. Immunology 16 779-784, 1969. 

The Diagnosis of Deficiencies of Vitanun Bn and Intrinsic Factor in Man 153 Castle s Intrinsic Factor. 154... 

Loss of Castle s intrinsic factor leads to defective absorption of vitamin B12, and so to depletion. 

For several years Glass and his colleagues (1952) have held the view that Castle s intrinsic factor was identical with or associated with the soluble glandular mucoprotein fraction of normal gastric juice. This muco-protein was believed to come from the cells at the neck of glands in the fundus (corpus) mucosa of the human stomach. During electrophoresis this substance moved towards the anode, and was the most acid protein in gastric juice. 

The suggestion of Glass et al. (1954) that in addition to Castle s intrinsic factor there may be an intramural intestinal Bu acceptor (analo ... 

The authors suggest that in addition to Castle s intrinsic factor there may be an intramural intestinal B12 acceptor (analogous to apoferritin in iron absorption) which may be responsible for the partial mucosal block to Bi2 absorption in the intestine of normal human beings. A similar mechanism may be responsible for limiting the amount of B12 which can be absorbed even with added intrinsic factor in patients with pernicious anemia (see page 163). 

In conclusion, it must be emphasized that these conclusions are tentative and that much remains to be learned about the nature and action of Castle s intrinsic factor. 

Meyer et al. (1950) described responses to the oral administration of a preparation containing 1.67 mg. of folic acid and 25 ng. of vitamin B12 on the assumption that neither agent would have had any significant hemopoietic effect, they concluded that foUc acid acted like the intrinsic factor. Welch and Nichol (1952) demonstrated that folic acid did not enhance the absorption of an, orally administered dose of radioactive vitamin B12, and could therefore not be said to be active like Castle s intrinsic factor. 

Pernicious anemia is primarily a deficiency of vitamin Bis due to permanent loss of Castle s intrinsic factor. Treatment with Bis is usually all that is required. In the initial stages there may be a temporary deficiency of folic acid or ascorbic acid, but there is seldom any need to administer these substances so long as enough Bis is given and the patient takes a good diet. 

Next, vitamin B-12 is bound to a highly specific glycoprotein, Castle s intrinsic factor, which is secreted in the stomach. 

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