Effect of folate-binding protein on intestinal transport of folic acid and 5-methyltetrahydrofolate across Caco-2 cells
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...
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| Veröffentlicht in: | European journal of nutrition 2005-06, Vol.44 (4), p.242-249 |
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| creator | VERWEI, Miriam VAN DEN BERG, Henk HAVENAAR, Robert GROTEN, John P |
| description | 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.
To investigate the effect of FBP on the absorption of folic acid and 5-CH3-H4folate from the intestinal lumen.
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.
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.
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. |
| doi_str_mv | 10.1007/s00394-004-0516-9 |
| format | Article |
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To investigate the effect of FBP on the absorption of folic acid and 5-CH3-H4folate from the intestinal lumen.
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.
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.
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.</description><identifier>ISSN: 1436-6207</identifier><identifier>EISSN: 1436-6215</identifier><identifier>DOI: 10.1007/s00394-004-0516-9</identifier><identifier>PMID: 15316828</identifier><language>eng</language><publisher>Heidelberg: Springer</publisher><subject>Biological and medical sciences ; Biological Transport - drug effects ; Caco-2 Cells ; Carrier Proteins - metabolism ; Carrier Proteins - pharmacology ; Cell Culture Techniques ; Chromatography, Gel ; Feeding. Feeding behavior ; Folate Receptors, GPI-Anchored ; Folic Acid - metabolism ; Fundamental and applied biological sciences. Psychology ; Humans ; Intestinal Absorption ; Intestine, Small - metabolism ; Receptors, Cell Surface - metabolism ; Tetrahydrofolates - metabolism ; Time Factors ; Vertebrates: anatomy and physiology, studies on body, several organs or systems</subject><ispartof>European journal of nutrition, 2005-06, Vol.44 (4), p.242-249</ispartof><rights>2005 INIST-CNRS</rights><rights>Steinkopff Verlag 2005</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c356t-48de46b5284f473acd6b4d99f330010fd64715cb7ce3511635e388c05fa61a073</citedby><cites>FETCH-LOGICAL-c356t-48de46b5284f473acd6b4d99f330010fd64715cb7ce3511635e388c05fa61a073</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=16810277$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15316828$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>VERWEI, Miriam</creatorcontrib><creatorcontrib>VAN DEN BERG, Henk</creatorcontrib><creatorcontrib>HAVENAAR, Robert</creatorcontrib><creatorcontrib>GROTEN, John P</creatorcontrib><title>Effect of folate-binding protein on intestinal transport of folic acid and 5-methyltetrahydrofolate across Caco-2 cells</title><title>European journal of nutrition</title><addtitle>Eur J Nutr</addtitle><description>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.
To investigate the effect of FBP on the absorption of folic acid and 5-CH3-H4folate from the intestinal lumen.
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.
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.
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.</description><subject>Biological and medical sciences</subject><subject>Biological Transport - drug effects</subject><subject>Caco-2 Cells</subject><subject>Carrier Proteins - metabolism</subject><subject>Carrier Proteins - pharmacology</subject><subject>Cell Culture Techniques</subject><subject>Chromatography, Gel</subject><subject>Feeding. Feeding behavior</subject><subject>Folate Receptors, GPI-Anchored</subject><subject>Folic Acid - metabolism</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Humans</subject><subject>Intestinal Absorption</subject><subject>Intestine, Small - metabolism</subject><subject>Receptors, Cell Surface - metabolism</subject><subject>Tetrahydrofolates - metabolism</subject><subject>Time Factors</subject><subject>Vertebrates: anatomy and physiology, studies on body, several organs or systems</subject><issn>1436-6207</issn><issn>1436-6215</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2005</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><recordid>eNpdkUuLVDEQhYMozkN_gBsJgrOLVm6edynN-IABN7oOuXk4GW4nbZJG-t-btlsHXITK4juHOnUQekXhHQVQ7xsAmzkBGE9QSeYn6JJyJomcqHj67w_qAl219gAAE5P0ObqgglGpJ32Jft3GGFzHJeJYVtsDWVL2Kf_Au1p6SBmXjFPuofWU7Yp7tbntSv2rSA5blzy22WNBtqHfH9YeBnV_8LWcLAdRS2t4Y10hE3ZhXdsL9CzatYWX53mNvn-8_bb5TO6-fvqy-XBHHBOyE6594HIRk-aRK2adlwv38xwZA6AQveSKCrcoF5igVDIRmNYORLSSWlDsGt2cfEecn_uRwmxTO25gcyj7ZqTSsxQTHeCb_8CHsq8jcjMT5VoKNbMB0RP0J1AN0exq2tp6MBTMsRJzqsSMSsyxEjMPzeuz8X7ZBv-oOHcwgLdnwDZn1zgu7FJ75KSmMCnFfgPKPJPO</recordid><startdate>20050601</startdate><enddate>20050601</enddate><creator>VERWEI, Miriam</creator><creator>VAN DEN BERG, Henk</creator><creator>HAVENAAR, Robert</creator><creator>GROTEN, John P</creator><general>Springer</general><general>Springer Nature B.V</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7QP</scope><scope>7RQ</scope><scope>7RV</scope><scope>7TS</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9-</scope><scope>K9.</scope><scope>KB0</scope><scope>M0R</scope><scope>M0S</scope><scope>M1P</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>7X8</scope></search><sort><creationdate>20050601</creationdate><title>Effect of folate-binding protein on intestinal transport of folic acid and 5-methyltetrahydrofolate across Caco-2 cells</title><author>VERWEI, Miriam ; VAN DEN BERG, Henk ; HAVENAAR, Robert ; GROTEN, John P</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c356t-48de46b5284f473acd6b4d99f330010fd64715cb7ce3511635e388c05fa61a073</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2005</creationdate><topic>Biological and medical sciences</topic><topic>Biological Transport - drug effects</topic><topic>Caco-2 Cells</topic><topic>Carrier Proteins - metabolism</topic><topic>Carrier Proteins - pharmacology</topic><topic>Cell Culture Techniques</topic><topic>Chromatography, Gel</topic><topic>Feeding. Feeding behavior</topic><topic>Folate Receptors, GPI-Anchored</topic><topic>Folic Acid - metabolism</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Humans</topic><topic>Intestinal Absorption</topic><topic>Intestine, Small - metabolism</topic><topic>Receptors, Cell Surface - metabolism</topic><topic>Tetrahydrofolates - metabolism</topic><topic>Time Factors</topic><topic>Vertebrates: anatomy and physiology, studies on body, several organs or systems</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>VERWEI, Miriam</creatorcontrib><creatorcontrib>VAN DEN BERG, Henk</creatorcontrib><creatorcontrib>HAVENAAR, Robert</creatorcontrib><creatorcontrib>GROTEN, John P</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Career & Technical Education Database</collection><collection>Nursing & Allied Health Database</collection><collection>Physical Education Index</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>Consumer Health Database (Alumni Edition)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Consumer Health Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Nursing & Allied Health Premium</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><jtitle>European journal of nutrition</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>VERWEI, Miriam</au><au>VAN DEN BERG, Henk</au><au>HAVENAAR, Robert</au><au>GROTEN, John P</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Effect of folate-binding protein on intestinal transport of folic acid and 5-methyltetrahydrofolate across Caco-2 cells</atitle><jtitle>European journal of nutrition</jtitle><addtitle>Eur J Nutr</addtitle><date>2005-06-01</date><risdate>2005</risdate><volume>44</volume><issue>4</issue><spage>242</spage><epage>249</epage><pages>242-249</pages><issn>1436-6207</issn><eissn>1436-6215</eissn><abstract>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.
To investigate the effect of FBP on the absorption of folic acid and 5-CH3-H4folate from the intestinal lumen.
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.
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.
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.</abstract><cop>Heidelberg</cop><pub>Springer</pub><pmid>15316828</pmid><doi>10.1007/s00394-004-0516-9</doi><tpages>8</tpages></addata></record> |
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| ispartof | European journal of nutrition, 2005-06, Vol.44 (4), p.242-249 |
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| subjects | Biological and medical sciences Biological Transport - drug effects Caco-2 Cells Carrier Proteins - metabolism Carrier Proteins - pharmacology Cell Culture Techniques Chromatography, Gel Feeding. Feeding behavior Folate Receptors, GPI-Anchored Folic Acid - metabolism Fundamental and applied biological sciences. Psychology Humans Intestinal Absorption Intestine, Small - metabolism Receptors, Cell Surface - metabolism Tetrahydrofolates - metabolism Time Factors Vertebrates: anatomy and physiology, studies on body, several organs or systems |
| title | Effect of folate-binding protein on intestinal transport of folic acid and 5-methyltetrahydrofolate across Caco-2 cells |
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