Cobalamin-specific R binder in pernicious anemia gastric juice: production by digestive enzyme action on saliva R binder.
We found in four of five pernicious anemia gastric juices a partly degraded R binder which was cobalamin specific and has an apparent molecular weight of 60-70,000 daltons. Twenty-nine to 74% (4.8-27.0 ng/ml) of the corrinoid binding capacity could not be blocked by cobinamide (a noncobalamin corrinoid). The fifth pernicious anemia gastric juice and five nonpernicious anemia gastric juices had minimal amounts of this binder (2.5 and 2.2 +/- 1.4 ng/ml). Scatchard analysis revealed that cobalamin-specific R binder has 1000-fold lower affinity for cobinamide than cobalamin. Increasing quantities of trypsin and/or chymotrypsin digested increasing amounts of saliva R binder and an increasing percentage of the remaining digest-resistant R binder acquired cobalamin specificity. Partly degraded R binder in pernicious anemia gastric juice was resistant to further proteolysis. Cobalamin-specific R binder, perhaps produced in vivo by the action of refluxed pancreatic enzymes on swallowed R would preferentially bind ingested and/or biliary cobalamin rather than analogue and thereby could play a role in hastening the development of cobalamin deficiency in pernicious anemia.
D000740:Anemia / Q000378:metabolism; D000752:Anemia, Pernicious / Q000378:metabolism*; D002850:Chromatography, Gel; D003038:Cobamides / Q000032:analysis; D005750:Gastric Juice / Q000032:analysis*; D006801:Humans; D007437:Intrinsic Factor / Q000032:analysis*; D008970:Molecular Weight; D010179:Pancreas / Q000201:enzymology; D011956:Receptors, Cell Surface / Q000032:analysis*; D012463:Saliva / Q000032:analysis*; D014805:Vitamin B 12 / Q000032:analysis*
D003038:Cobamides; D011956:Receptors, Cell Surface; C029486:intrinsic factor-cobalamin receptor; C017142:cobinamide; D007437:Intrinsic Factor; D014805:Vitamin B 12