Title
Effect of folate-binding protein on intestinal transport of folic acid and 5-methyltetrahydrofolate across Caco-2 cells
Author
Verwei, M.
van den Berg, H.
Havenaar, R.
Groten, J.P.
TNO Defensie en Veiligheid TNO Kwaliteit van Leven
Publication year
2005
Abstract
Background: Milk products are a potential matrix for fortification with synthetic folic acid or natural 5-methyltetrahydrofolate (5-CH 3-H4folate) to enhance the daily folate intake. In milk, folate occurs bound to folatebinding proteins (FBP). Our previous studies with an in vitro gastrointestinal model showed that 70% of the initial FBP content of the milk product was retained in the duodenal lumen. While folic acid remained bound to FBP after gastric passage, 5-CH3-H4folate was mainly present as free folate in the duodenal lumen. Aim of the study: To investigate the effect of FBP on the absorption of folic acid and 5-CH 3-H4folate from the intestinal lumen. Methods: The transport of [3H]-folic acid and [14C]-5-CH 3-H4folate across enterocytes was studied in the presence or absence of bovine FBP using monolayers of Caco-2 cells grown on semi-permeable inserts in a two-compartment model. The apparent permeability coefficients (Papp) of folic acid and 5-CH3-H 4folate were determined and compared with the permeability of reference compounds for low (mannitol) and high (caffeine) permeability. Results: The transport from the apical to the basolateral side of the Caco-2 cells was higher (P < 0.05) for folic acid (Papp = 1.7*10-6 cm/s) than for 5- CH3-H4folate (Papp = 1.4*10-6 cm/s) after 2 h incubation to 1 μM folic acid or 5-CH3-H4folate test solutions (pH 7). The permeability of folic acid and 5-CH3-H4folate across Caco-2 monolayers appeared to be higher (P < 0.05) than that of mannitol (Papp = 0.5*10-6 cm/s) but lower (P < 0.05) than that of caffeine (Papp = 34*10-6 cm/s). The addition of FBP to the medium led to a lower (P < 0.05) intestinal transport and cellular accumulation of folic acid and 5-CH3-H4folate. Conclusions: Compared to the reference compounds, folic acid and 5-CH 3-H4folate showed a moderate permeability across Caco-2 cells, which indicates that folate absorption from the intestinal lumen is not likely to be complete. The intestinal transport of folic acid and 5-CH 3-H4folate was found to be dependent on the extent of binding to FBP at the luminal side of the cells. © Steinkopff Verlag 2004.
Subject
Biology
Biomedical Research
Bioavailability
Caco-2
Folate
Folate-binding protein
Intestinal transport
5 methyltetrahydrofolic acid
caffeine
folate binding protein
folic acid
mannitol
article
cell growth
cell membrane permeability
controlled study
human
human cell
intestine absorption
intestine cell
monolayer culture
protein binding
Biological Transport
Caco-2 Cells
Carrier Proteins
Cell Culture Techniques
Chromatography, Gel
Folic Acid
Humans
Intestinal Absorption
Intestine, Small
Receptors, Cell Surface
Tetrahydrofolates
Time Factors
Bovinae
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http://resolver.tudelft.nl/uuid:2c413eb6-524d-4a7f-b041-7da2d294434e
DOI
https://doi.org/10.1007/s00394-004-0516-9
TNO identifier
238514
ISSN
1436-6207
Source
European Journal of Nutrition, 44 (4), 242-249
Document type
article