Abstract
Cobalamin (Cbl) and its Cbl-binding proteins are present in amniotic fluid. Because amniotic fluid is swallowed by the embryo-fetus, we studied the ability of Cbl to be transported and metabolized across the embryo-fetal digestive tract. Human embryonic stomachs and intestines were transplanted into nude mice. The basal secretion of Cbl-binding proteins was studied by gel filtration of the graft juices. Intrinsic factor (IF) was looked for in gastric mucosa by immunohistochemistry. The uptake of [57Co]-labeled Cbl by the intestinal graft was studied by Schilling tests and HPLC. IF, haptocorrin, and a transcobalamin-like protein were detected in gastric juice, with concentration ranges of 5.0-26.4, 1.9-27.1, and 5.2-12.6 pmol/mL, respectively. The IF [57Co]Cbl complex had a single isoprotein with a pI at 5.6, which was maintained after incubation with neuraminidase. Urine excretion percentages (Schilling tests) ranged from 5.5 to 21.2% and from 0.3 to 1.6% when cyano-[57Co]Cbl-IF or cyano-[57Co]Cbl, respectively, was instilled in intestinal grafts. Chloroquine reduced significantly the percentage of excreted [57Co]Cbl. The [57Co]Cbl was mainly excreted as cyano-[57Co]Cbl in urines, showing a low coenzyme conversion. In conclusion, IF is secreted by the nonstimulated embryonic stomach and lacks sialic acid. Cbl binds to it and is subsequently transported across the xenografted embryo-fetal intestine. This suggests that amniotic fluid may contribute to Cbl delivery to the embryo-fetus.
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Abbreviations
- Ado-Cbl:
-
ado-cobalamin
- Cbl:
-
cobalamin
- Cbl-IF:
-
cobalamin-intrinsic factor complex
- CN-Cbl:
-
cyanocobalamin
- HC:
-
haptocorrin
- IF:
-
intrinsic factor
- Me-Cbl:
-
methylcobalamin
- OH-Cbl:
-
hydroxocobalamin
- TC:
-
transcobalamin
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Aimone-Gastin, I., Gueant, J., Plenat, F. et al. Assimilation of [57Co]-Labeled Cobalamin in Human Fetal Gastrointestinal Xenografts into Nude Mice. Pediatr Res 45, 860–866 (1999). https://doi.org/10.1203/00006450-199906000-00014
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DOI: https://doi.org/10.1203/00006450-199906000-00014
