title: Transcobalamin derived from bovine milk stimulates apical uptake of vitamin B12 into human intestinal epithelial cells.
abstract: Intestinal uptake of vitamin B12 (hereafter B12) is impaired in a significant proportion of the human population. This impairment is due to inherited or acquired defects in the expression or function of proteins involved in the binding of diet-derived B12 and its uptake into intestinal cells. Bovine milk is an abundant source of bioavailable B12 wherein it is complexed with transcobalamin. In humans, transcobalamin functions primarily as a circulatory protein, which binds B12 following its absorption and delivers it to peripheral tissues via its cognate receptor, CD320. In the current study, the transcobalamin-B12 complex was purified from cows' milk and its ability to stimulate uptake of B12 into cultured bovine, mouse and human cell lines was assessed. Bovine milk-derived transcobalamin-B12 complex was absorbed by all cell types tested, suggesting that the uptake mechanism is conserved across species. Furthermore, the complex stimulated the uptake of B12 via the apical surface of differentiated Caco-2 human intestinal epithelial cells. These findings suggest the presence of an alternative transcobalamin-mediated uptake pathway for B12 in the human intestine other than that mediated by the gastric glycoprotein, intrinsic factor. Our findings highlight the potential for transcobalamin-B12 complex derived from bovine milk to be used as a natural bioavailable alternative to orally administered free B12 to overcome B12 malabsorption.
authors.affiliation: CSIRO, Animal, Food & Health Sciences, Armidale, NSW, 2350, Australia.
authors.forename: Brad
authors.initials: B
authors.lastname: Hine
authors.forename: Irina
authors.initials: I
authors.lastname: Boggs
authors.forename: Ralph
authors.initials: R
authors.lastname: Green
authors.forename: Joshua W
authors.initials: JW
authors.lastname: Miller
authors.forename: Russell C
authors.initials: RC
authors.lastname: Hovey
authors.forename: Rex
authors.initials: R
authors.lastname: Humphrey
authors.forename: Thomas T
authors.initials: TT
authors.lastname: Wheeler
mesh_terms: D000818:Animals; D018938:Caco-2 Cells; D002417:Cattle; D002460:Cell Line; D004847:Epithelial Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000166:cytology*; D014155:Transcobalamins / Q000494:pharmacology*; D014805:Vitamin B 12 / Q000378:metabolism*
chemical_list: D014155:Transcobalamins; D014805:Vitamin B 12
keywords: COBALAMIN; Caco-2; MALABSORPTION; MILK