Folic Acid Uptake and Its Regulation in the Placenta

2015 ◽  
pp. 192-209 ◽  
Keyword(s):  
Folic Acid ◽  
Acid Uptake

Renal folate absorption and the kidney folate binding protein. II. Microinfusion studies

1987 ◽  
Vol 252 (4) ◽  
pp. F757-F760 ◽  
Author(s):  
J. Selhub ◽  
S. Nakamura ◽  
F. A. Carone
Keyword(s):  
Folic Acid ◽  
Brush Border ◽  
Half Life ◽  
Binding Protein ◽  
Membrane Surface ◽  
Rapid Change ◽  
Acid Uptake ◽  
Folate Binding Protein ◽  
Acid Absorption ◽  
Folic Acid Absorption

Surface proximal convoluted tubules (PCT) in rats were microinfused in situ with [3H]folic acid to study the role of folate binding protein (FBP) in the kidney brush-border membrane for renal conservation and transport of folate [3H]folic acid absorption was linearly related to tubular length of PCT and occurred largely in this segment of the tubule. Unlabeled folate derivatives inhibited [3H]folic acid absorption, the extent of which was dependent on the type of unlabeled folate used and its concentration. At equivalent concentrations, inhibition was most effective with unlabeled folic acid, slightly lower than with 5-methyltetrahydrofolate and least effective with methotrexate. Comparisons between [3H]folic acid absorption before and after infusion of a saturating dose of unlabeled folic acid or repetitive injections of [3H]folic acid into the same tubular site revealed continuous and rapid regeneration of unsaturated folic acid uptake sites with an apparent half-life of 28.75 +/- 8.75 s. Determination of [3H] retained in the tubule at various periods after microinfusion of [3H]folic acid revealed slow cellular disappearance with an apparent half-life of 47.3 +/- 5.4 min. It is proposed that the brush-border FBP functions as a receptor of infused folic acid and that following the binding of the ligand the folic acid/FBP complex undergoes a rapid change that results in the internalization of folic acid and regeneration of unsaturated binding sites at the membrane surface. Internalized folic acid is slowly released into renal capillaries.

Role of sodium ion in transport of folic acid in the small intestine

1986 ◽  
Vol 251 (2) ◽  
pp. G218-G222 ◽  
Author(s):  
J. Zimmerman ◽  
J. Selhub ◽  
I. H. Rosenberg
Keyword(s):  
Small Intestine ◽  
Folic Acid ◽  
Brush Border ◽  
Brush Border Membrane ◽  
Membrane Vesicles ◽  
Test Solution ◽  
Brush Border Membrane Vesicles ◽  
Acid Uptake ◽  
Folate Transport ◽  
Luminal Membrane

The effect of sodium on folate transport across the intestinal luminal membrane was analyzed using two techniques: the "influx" chamber and isolated brush-border membrane vesicles. Preincubation of tissue in Na+-free medium did not have a consistent effect on folic acid influx provided that Na+ was present in the test solution. Replacement of Na+ in the test solution by choline+ resulted in a significant reduction of folic acid influx. However, when intestinal sheets that had been equilibrated in Na+-free solution were exposed to test solution containing either Na+, Li+, K+, Rb+, Cs+, Tris+, or guanidinium+ as main cations, folic acid influx was not significantly decreased. Concentration-dependence studies showed that replacement of Na+ by Rb+ did not affect the saturable mechanism of folate transport. Rather, a decrease in nonsaturable folic acid uptake accounted for the slightly reduced influx observed in the presence of Rb+. Experiments with brush-border membrane vesicles revealed that methotrexate uptake was significantly higher in the presence of external Na+ than in the presence of K+, but was not different from uptake in the presence of K+ plus valinomycin. These data suggest that the saturable component of folate transport is not Na+ dependent, and nonsaturable transport of folic acid across the luminal membrane occurs in part through a conductive pathway that involves a negatively charged species of folate and a cation whose membrane permeability affects the rate of folate transport. The importance of Na+ in this process in vivo derives from the fact that Na+ is the most permeant cation available at the absorptive site in the small intestine.

Comparison of folic acid uptake characteristics by human placental choriocarcinoma cells at acidic and physiological pH

2006 ◽  
Vol 84 (2) ◽  
pp. 247-255 ◽  
Author(s):  
Elisa Keating ◽  
Clara Lemos ◽  
Isabel Azevedo ◽  
Fátima Martel
Keyword(s):  
Folic Acid ◽  
Cytochalasin D ◽  
Disulfonic Acid ◽  
Acid Uptake ◽  
Maternal Circulation ◽  
Human Trophoblast ◽  
Receptor Mediated Endocytosis ◽  
Bewo Cells ◽  
Carbonyl Cyanide ◽  
Choriocarcinoma Cells

The aim of this work was to characterize the placental uptake of folic acid from the maternal circulation. Using 2 human trophoblast cell lines (BeWo and JAR), we verified that uptake of 3H-folic acid was pH-dependent, increasing significantly with decreasing extracellular pH. In BeWo cells, uptake of 3H-folic acid at pH 5.5 was (i) Na+-independent; (ii) inhibited by folic acid, 5-methyltetrahydrofolate (5-MTHF), and methotrexate (MTX); (iii) inhibited by the anion transport inhibitors 4,4′-diisothiocyanatostilbene-2,2′-disulphonic acid (DIDS) and 4-acetamido-4′-isothiocyano-2,2′-disulfonic acid stilbene (SITS); (iv) inhibited by the proton ionophore carbonyl cyanide 4-(trifluoromethoxy)phenylhydrazone (FCCP); (v) not inhibited by blockers of receptor-mediated endocytosis (cytochalasin D and monensin); (vi) trans-inhibited by MTX and folic acid; and (vii) not affected by an anti-reduced folate transporter-1 (RFC) antibody. At pH 7.5, uptake of 3H-folic acid was (i) Na+-independent; (ii) inhibited by folic acid and MTX, but not by 5-MTHF; (iii) inhibited by SITS, but not by DIDS; (iv) not affected by FCCP; (v) inhibited by monensin (but not by cytochalasin D); (vi) trans-inhibited by folic acid (but not by MTX); and (vii) inhibited by an anti-RFC antibody. In conclusion, in BeWo cells, both RFC and receptor-mediated endocytosis seem to be involved in 3H-folic acid uptake at pH 7.5, whereas at pH 5.5, RFC and (or) a low pH-operating transporter distinct from RFC are involved.

Folic acid uptake by the human syncytiotrophoblast: Interference by pharmacotherapy, drugs of abuse and pathological conditions

2009 ◽  
Vol 28 (4) ◽  
pp. 511-520 ◽  
Author(s):  
Elisa Keating ◽  
Pedro Gonçalves ◽  
Isabel Campos ◽  
Fernanda Costa ◽  
Fátima Martel
Keyword(s):  
Folic Acid ◽  
Drugs Of Abuse ◽  
Acid Uptake ◽  
Pathological Conditions

scholarly journals Folic acid uptake by the human syncytiotrophoblast is affected by gestational diabetes, hyperleptinemia, and TNF-α

2013 ◽  
Vol 73 (1-4) ◽  
pp. 388-394 ◽  
Author(s):  
João R. Araújo ◽  
Ana Correia-Branco ◽  
Liliana Moreira ◽  
Carla Ramalho ◽  
Fátima Martel ◽  
...  
Keyword(s):  
Folic Acid ◽  
Gestational Diabetes ◽  
Acid Uptake ◽  
Tnf Α

Intracellular regulation of intestinal folate uptake: studies with cultured IEC-6 epithelial cells

1997 ◽  
Vol 272 (2) ◽  
pp. C729-C736 ◽  
Author(s):  
H. M. Said ◽  
T. Y. Ma ◽  
A. Ortiz ◽  
A. Tapia ◽  
C. K. Valerio
Keyword(s):  
Small Intestine ◽  
Folic Acid ◽  
Protein Kinase ◽  
Epithelial Cell ◽  
Intestinal Epithelial Cell ◽  
Acid Uptake ◽  
Maximal Velocity ◽  
Intestinal Epithelial ◽  
Intracellular Regulation ◽  
Uptake Process

Although the mechanism of folate uptake in the small intestine has been well characterized, very little is known about the intracellular regulation of the uptake process. Using mature confluent monolayers of the intestinal epithelial cell line IEC-6 as an in vitro intestinal epithelial cell model, we have found the uptake of folic acid to be similar to that of the native small intestine in that it is 1 ) temperature, energy, and pH dependent, 2) Na+ independent, 3) inhibited by structural analogs and anion transport inhibitors, and 4) saturable as a function of substrate concentration [apparent Michaelis constant (Km) = 0.45 +/- 0.06 microM; maximal velocity (Vmax) = 3.08 +/- 0.14 pmol x mg protein(-1) x 5 min(-1)]. Furthermore, IEC-6 cells were found by Northern blot analysis to lack the expression of the membrane folate-binding protein. Pretreatment of IEC-6 monolayers with specific protein tyrosine kinase (PTK) inhibitors genistein and tyrphostin A25 caused a significant inhibition in folic acid uptake. On the other hand, their negative controls, genistin and tyrphostin A1, respectively, had no effect. The inhibitory effect of genistein was mediated through inhibition in the Vmax of the folate uptake process with no change in the apparent Km. Pretreatment of IEC-6 monolayers with compounds that increase intracellular adenosine 3',5'-cyclic monophosphate (cAMP) level (e.g., dibutyryl cAMP) also resulted in a significant (though modest) inhibition in folic acid uptake; however, specific inhibitors of protein kinase A did not affect the uptake process. Specific modulators of protein kinase C and Ca2+/calmodulin-mediated pathways did not significantly affect folic acid uptake. These results demonstrate the suitability of IEC-6 monolayers as an intestinal epithelial model to study folate transport and demonstrate for the first time that uptake of folic acid is regulated by a PTK- and a cAMP-mediated pathway.

scholarly journals Haem and folate transport by proton-coupled folate transporter/haem carrier protein 1 (SLC46A1)

2008 ◽  
Vol 101 (8) ◽  
pp. 1150-1156 ◽  
Author(s):  
Abas H. Laftah ◽  
Gladys O. Latunde-Dada ◽  
Sarah Fakih ◽  
Robert C. Hider ◽  
Robert J. Simpson ◽  
...  
Keyword(s):  
Folic Acid ◽  
Cultured Cells ◽  
Physiological Role ◽  
Carrier Protein ◽  
Acid Uptake ◽  
Folate Transport ◽  
Blocking Antibody ◽  
Interfering Rna

Haem carrier protein 1 (HCP1) was originally identified and characterised as a mammalian haem transporter. However, recent evidence has shown that it is also a proton-coupled folate transporter (PCFT) and mutations in the gene cause hereditary folate deficiency in humans. We therefore investigated haem and folate transport characteristics of PCFT/HCP1 bothin vivoandin vitroin CD-1 mice and in the presence or absence of a blocking antibody for PCFT/HCP1, and also in cultured cells (which express PCFT/HCP1 endogenously) to elucidate the specificity and selectivity of PCFT/HCP1. Thein vivostudy showed that the addition of folic acid inhibited59Fe-labelled haem transport in hypoxic mice but had no effect in normal mice. Usingin vitromethods, the results showed increased [3H]folate uptake into everted duodenum from hypoxic mice but uptake was reduced by the addition of haem or PCFT/HCP1 antibodies to the medium. Caco-2 cells transiently transfected with small interfering RNA (siRNA) PCFT/HCP1 duplex oligos resulted in a 69 % reduction in PCFT/HCP1 mRNA when compared with the control siRNA. Both haem and folate uptake were significantly (P < 0·05) reduced in cells transfected with PCFT/HCP1 siRNA; however, the magnitude of reduction with folic acid uptake was greater (48 %) than that of haem (22·5 %). Overall the data support PCFT/HCP1 as a primary folate transporter with a lower affinity for haem. PCFT/HCP1 could therefore play a physiological role in Fe nutrition and the data highlight the potential for the interaction of folate and haem at the level of intestinal absorption.

The Effect of Vitamin B12 and Methionine on Folic Acid Uptake by Rat Liver

1971 ◽  
Vol 136 (1) ◽  
pp. 42-46 ◽  
Author(s):  
J. M. Gawthorne ◽  
E. L. R. Stokstad
Keyword(s):  
Folic Acid ◽  
Vitamin B12 ◽  
Rat Liver ◽  
Acid Uptake
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