intrinsic-factor and Cystic-Fibrosis

Absorption of crystalline labeled cobalamin is strongly decreased in cases of cystic fibrosis. In order to determine if this is due to an alteration or a lack of activation of intrinsic factor by proteases, the physicochemical properties and biological activity of intrinsic factor have been studied. Intrinsic factor was purified 800-fold from stimulated gastric juice of cystic fibrosis patients with a yield of 64.2%. Cystic fibrosis intrinsic factor had an estimated Mr of 57,000 in SDS-polyacrylamide gel electrophoresis. Its carbohydrate content resembled that of normal human intrinsic factor, except that the ratio fucose/sialic acid was higher (6.1 and 1.6, respectively) and that the content in N-acetylgalactosamine was decreased. The same alterations in carbohydrate composition were observed for Hc purified from cystic fibrosis saliva. Purified intrinsic factor from cystic fibrosis gastric juice was biologically active in vitro in the presence of ileal solubilized receptor as well as in vivo (Schilling test). The fate of iodinated cystic fibrosis intrinsic factor in guinea pig ileum studied by high-resolution radioautography was similar to that of normal intrinsic factor. In conclusion, despite modifications of the carbohydrate content of the molecule, the biological activity of intrinsic factor is not altered in cases of cystic fibrosis. The malassimilation of crystalline cobalamin observed in cystic fibrosis is due to a mechanism independent from intrinsic factor secretion.

Topics: Animals; Carbohydrates; Chromatography, Affinity; Chromatography, Ion Exchange; Cystic Fibrosis; Electrophoresis; Female; Gastric Juice; Guinea Pigs; Humans; Intrinsic Factor; Isoelectric Focusing; Pentagastrin; Transcobalamins; Vitamin B 12

A malabsorption of crystalline labelled cobalamin is observed in 100% of cystic fibrosis patients. Using radioisotope dilution assays and molecular sieve gel chromatography, we determined the serum concentration and the faecal excretion of cobalamin and cobalamin analogues in nine cystic fibrosis children before and after 4 days' interruption of pancreatic extract treatment. On chromatography, the unsaturated cobalamin binders of the faecal extracts eluted in two positions with molecular masses of 44 300 and 20 300, corresponding mostly to partially degraded R binders. The amounts of the less degraded form of R binder (molecular mass 44 300) increased significantly after interruption of the treatment. The cobalamin concentration in the serum remained normal after interruption of the treatment but the analogue concentrations in the serum decreased and faecal excretion of cobalamin and analogues increased significantly. These results allowed us to suggest that (1) pancreatic insufficiency in cystic fibrosis is responsible for a decrease in the absorption of digestive analogues induced by a defective degradation of R binders, and (2) cobalamin analogues have a short half-life in blood.

Topics: Adolescent; Carrier Proteins; Child; Child, Preschool; Chromatography, Gel; Cystic Fibrosis; Feces; Half-Life; Humans; Intestinal Absorption; Intrinsic Factor; Pancreatic Extracts; Vitamin B 12

Topics: Adult; Child, Preschool; Cystic Fibrosis; Diabetes Complications; Dysgammaglobulinemia; Female; Humans; Immunoglobulin A; Immunoglobulin kappa-Chains; Immunoglobulin lambda-Chains; Immunoglobulin Light Chains; Immunologic Deficiency Syndromes; Intrinsic Factor; Malabsorption Syndromes; Male

Topics: Biological Availability; Child; Child, Preschool; Cobalt Radioisotopes; Cystic Fibrosis; Dietary Proteins; Food; Humans; Intestinal Absorption; Intrinsic Factor; Iron; Iron Radioisotopes; Liver; Meat; Pancreatin; Protein Binding; Radioisotopes; Selenium; Selenomethionine; Vitamin B 12; Vitamin B 12 Deficiency; Whole-Body Counting