Evidence that pancreatic proteases enhance vitamin B12 absorption by acting on curde preparations of hog gastric intrinsic factor and human gastric juice.
Crude preparations of hog gastric intrinsic factor or their own previously collected gastric juices administered with labeled vitamin B12 did not enhance vitamin B12 absorption in patients with vitamin B12 malabsorption secondary to pancreatic insufficiency. However, when these sources of gastric intrinsic factor were incubated with three times crystallized preparations of insolubilized bovine trypsin or chymotrypsin, the proteolytic enzymes were removed by centrifugation, and the preparations of gastric intrinsic factor were readministered to these patients, the absorption of vitamin B12 was markedly enhanced. Studies of hog gastric intrinsic factor before and after exposure to proteolytic enzymes failed to show any difference on Sephadex chromatography or polyacrylamide gel electrophoresis or on its affinity for vitamin B12 or the ileal receptor in guinea pigs. These investigations demonstrate that: (1) gastric intrinsic factor as secreted by subjects with pancreatic insufficiency or obtained from hog pyloric mucosal extracts is ineffective in promoting vitamin B12 absorption in patients with pancreatic insufficiency, (2) incubation of crude preparations of gastric intrinsic factor with insolubilized pancreatic proteases modified these preparations of gastric intrinsic factor in an as yet undefined manner, allowing them to enhance vitamin B12 absorption, and (3) in vitro studies using gut sacs or brush border preparations do not reflect the abnormality in vitamin B12 absorption associated with pancreatic dysfunction.
D000752:Anemia, Pernicious / Q000150:complications / Q000503:physiopathology; D000818:Animals; D002918:Chymotrypsin / Q000494:pharmacology; D002986:Clinical Trials as Topic; D005260:Female; D005750:Gastric Juice / Q000187:drug effects*; D006168:Guinea Pigs; D006801:Humans; D007408:Intestinal Absorption / Q000187:drug effects; D007437:Intrinsic Factor / Q000032:analysis / Q000627:therapeutic use*; D010182:Pancreatic Diseases / Q000150:complications* / Q000503:physiopathology; D010189:Pancreatic Juice / Q000201:enzymology; D010447:Peptide Hydrolases / Q000627:therapeutic use*; D013552:Swine; D014357:Trypsin / Q000494:pharmacology; D014806:Vitamin B 12 Deficiency / Q000188:drug therapy* / Q000503:physiopathology
D007437:Intrinsic Factor; D010447:Peptide Hydrolases; D002918:Chymotrypsin; D014357:Trypsin