Document Detail


Effect of folate-binding protein on intestinal transport of folic acid and 5-methyltetrahydrofolate across Caco-2 cells.
MedLine Citation:
PMID:  15316828     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Milk products are a potential matrix for fortification with synthetic folic acid or natural 5-methyltetrahydrofolate (5-CH3-H4folate) to enhance the daily folate intake. In milk, folate occurs bound to folate-binding 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-CH3-H4folate from the intestinal lumen. METHODS: The transport of [3H]-folic acid and [14C]-5-CH3-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 (P(app)) of folic acid and 5-CH3-H4folate 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 (P(app) = 1.7*10(-6) cm/s) than for 5-CH3-H4folate (P(app) = 1.4*10(-6) cm/s) after 2 h incubation to 1 microM 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 (P(app) = 0.5*10(-6) cm/s) but lower (P < 0.05) than that of caffeine (P(app) = 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-CH3-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-CH3-H4folate was found to be dependent on the extent of binding to FBP at the luminal side of the cells.
Authors:
Miriam Verwei; Henk van den Berg; Robert Havenaar; John P Groten
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2004-08-17
Journal Detail:
Title:  European journal of nutrition     Volume:  44     ISSN:  1436-6207     ISO Abbreviation:  Eur J Nutr     Publication Date:  2005 Jun 
Date Detail:
Created Date:  2005-06-03     Completed Date:  2005-10-18     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  100888704     Medline TA:  Eur J Nutr     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  242-9     Citation Subset:  IM    
Affiliation:
Physiological Sciences Dept., TNO Nutrition and Food Research, 360, 3700 AJ, Zeist, The Netherlands. verwei@voeding.tno.nl
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MeSH Terms
Descriptor/Qualifier:
Biological Transport / drug effects
Caco-2 Cells
Carrier Proteins / metabolism,  pharmacology*
Cell Culture Techniques
Chromatography, Gel
Folic Acid / metabolism*
Humans
Intestinal Absorption
Intestine, Small / metabolism*
Receptors, Cell Surface / metabolism
Tetrahydrofolates / metabolism*
Time Factors
Chemical
Reg. No./Substance:
0/Carrier Proteins; 0/Receptors, Cell Surface; 0/Tetrahydrofolates; 0/folate-binding protein; 134-35-0/5-methyltetrahydrofolate; 59-30-3/Folic Acid

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