The Intraluminal Transport of Vitamin B 12 and the Exocrine Pancreatic Insufficiency

Summary

The vitamin B₁₂-binding proteins saturated or unsaturated with endogenous vitamin B₁₂ in human gastric and intestinal juice were characterized in terms of molecular size, reaction with specific anti-intrinsic factor and R-binder (also called non-IF, Cobalophilin, etc.) sera, and reaction with specific porcine intrinsic factor receptor. It is concluded that the intestinal juice contains only intrinsic factor whereas gastric juice contains in addition R-binders. It appears likely that the absence of R-binders in intestinal juice is due to degradation by pancreatic enzymes and this fully supports the suggestion that the vitamin B12 malabsorption in exocrine pancreatic insufficiency is due to the presence of undegraded R-binders. The presence of free and biologically active intrinsic factor in intestinal juice suggests that entero–hepatic circulation may play an important role in vitamin B₁₂ homeostasis.

Note added in proof. While this paper has been in revision, we have progressed with the identification of B₁₂-binders in intestinal juice collected (see Materials and Methods) from a patient with proven EPI. Figure 2 illustrates the radiochromatogram through Sephadex G200 of (⁵⁸Co) B₁₂ coupled to this intestinal juice. Contrary to the elution pattern observed when the intestinal juices from normal subjects were used, the protein bound ⁵⁸Coradioactivity now delineated into two peaks corresponding by position to R-binder and IF (cf. Figs. 1B and 2). That R type B₁₂-binding proteins were present in the EPI intestinal juice was subsequently confirmed by specific radioimmunoassay (17) where the incubation of the juice with an excess of blocking type antibody from a pernicious anemia serum reduced the UB₁₂BC of the juice from 16.0 ng B₁₂/ml to only 6.44 ng B₁₂/ml. Thus more than 40% of the UB₁₂BC in the EPI intestinal juice was due to a non-IF binding protein, i.e., to R-binder. This observation further supports the suggestion (8, 19) that the R-binders in the upper gastrointestinal system do remain undegraded in EPI.