Reduced folate carrier. Medical search. Frequent questions

Pralatrexate is a folate analog that inhibits folate metabolism, thus impeding the synthesis of amino acids and nucleic acid. (drugbank.com)
12 This reaction both increases cellular retention of pralatrexate for extended drug action and impedes the uptake of folate, also a substrate of FPGS, to further inhibit folate metabolism in cancer cells. (drugbank.com)
Involvement in purine metabolism leads to extracellular release of adenosine , which reduces inflammation. (turkupetcentre.net)
Given its key role in folate metabolism, the methylenetetra-hydrofolate dehydrogenase ( MTHFD1 ) could represent an attractive candidate in NTD etiology. (biomedcentral.com)
This leads to low CSF 5-methyltetrahydrofolate (5MTHF), the active folate metabolite, in the presence of normal folate metabolism outside the nervous system. (pediatricneurosciences.com)
Alterations in six metabolic pathways were found on D 17 and D 45, including variations in the level of alpha-linolenic acid metabolism, glycerophospholipid metabolism, pentose and glucuronate interconversions, glycerolipid metabolism, folate biosynthesis, and tyrosine metabolism. (nature.com)
Folate-dependent one carbon metabolism is a highly polymorphic pathway that regulates the distribution of one-carbon derivatives between DNA synthesis (proliferation) and DNA methylation (cell-specific gene expression and differentiation). (phoenixrising.me)
Folate metabolism plays an important role in DNA synthesis and cell proliferation. (technologypublisher.com)
Findings from experimental studies have indicated that thyroid hormones affect folate metabolism. (medscape.com)
Maternal gene polymorphisms involved in folate metabolism and risk of Down syndrome offspring: a meta-analysis. (cdc.gov)
Folate metabolism gene polymorphisms MTHFR C677T and A1298C and risk for Down syndrome offspring: a meta-analysis. (cdc.gov)

The proton-coupled folate transporter (PCFT) is ubiquitously expressed in solid tumors to which it delivers antifolates, particularly pemetrexed, into cancer cells. (aspetjournals.org)
Folate/folate derivative transporter, RFC1. (tcdb.org)
1] "Molecular cloning of the human placental folate transporter. (tcdb.org)
We tested the hypothesis that intrauterine growth restriction (IUGR) is associated with decreased folate transporter expression and activity in isolated syncytiotrophoblast microvillous plasma membranes (MVM). (bepress.com)
MVM was isolated and folate transporter protein expression was measured using Western blot and transporter activity was determined using radiolabelled methyltetrahydrofolic acid and rapid filtration. (bepress.com)
In normal cells, folates are taken in through the reduced folate carrier (RFC) or proton-coupled folate transporter (PCFT), which are membrane-spanning proteins that facilitate bidirectional transportation of reduced folate across the plasma membrane and endosome membranes [ 1 ]. (biomedcentral.com)
it is expressed ubiquitously in mammalian tissues, including intestinal and colonic epithelia, basolateral membrane of renal proximal tubules, and blood-brain barrier , and although usually it is considered to be a facilitative transporter, in case of negatively charged folates it can work strongly against concentration gradient. (turkupetcentre.net)
Proton-coupled folate transporter (PCFT, SLC46A1) is mainly located in the upper (acidic) part of the intestine , renal tubules, and also elsewhere in the body, also in several solid tumours . (turkupetcentre.net)
Synthesis and biological activity of a novel series of 6-substituted pyrrolo[2,3-d]pyrimidine thienoyl antifolate inhibitors of purine biosynthesis with selectivity for high affinity folate receptors and the proton-coupled folate transporter over the reduced folate carrier for cellular entry. (karmanos.org)
The reduced folate carrier (RFC, SLC19A1), thiamine transporter-1 (ThTr1, SLC19A2) and thiamine transporter-2 (ThTr2, SLC19A3) evolved from the same family of solute carriers. (elsevierpure.com)
The proton-coupled folate transporter (PCFT, SLC46A1) is the mechanism by which folates are absorbed across the apical-brush-border membrane of the proximal small intestine. (elsevierpure.com)

In addition to RFC and PCFT, a limited number of cells express folate receptors (FRs) that can mediate unidirectional transportation of folates into cells. (biomedcentral.com)
The high-affinity folate binding protein (FBP) exists in humans in four isoforms, folate receptors (FRα and FRβ, or FOLR1 and FOLR2) that are attached to the outer cell surface by glycosyl-phosphatidyl-inositol (GPI) link, and FRγ (FOLR3) that is a secretory protein, and expressed at much lower levels than FRα and FRβ. (turkupetcentre.net)
Folate receptors FRα and FRβ bind folate and its reduced forms, and are important in folate tissue uptake, and FRα especially in renal reabsorption. (turkupetcentre.net)
Two folate receptors (FOLR1 and FOLR2) mediate folate transport across epithelia by an endocytic process. (elsevierpure.com)
Zhao, R & Goldman, ID 2013, ' Folate and thiamine transporters mediated by facilitative carriers (SLC19A1-3 and SLC46A1) and folate receptors ', Molecular aspects of medicine , vol. 34, no. 2-3, pp. 373-385. (elsevierpure.com)
GPI-linked membrane folate receptors (MFRs) have been implicated in the receptor-mediated uptake of reduced folate cofactors and folate-based chemotherapeutic drugs. (rupress.org)
Typically, normal cells express low levels of folate receptors. (technologypublisher.com)

The FRA has a high affinity for both folate (folic acid) and 5MTHF derivatives. (autismfile.com)
The simultaneous administration of sulfasalazine and folic acid is regular practice in the therapy of inflammatory bowel diseases in order to maintain sufficient folate concentration in patients. (mdpi.com)
Folate (folic acid or vitamin B9) is essential for the biosynthesis of nucleotide bases and for many other methylation reactions. (biomedcentral.com)
In the liver OATs mediate the uptake of folic acid and release into the bile, enabling the extensive enterohepatic circulation of folates. (turkupetcentre.net)
FRδ (Juno, FOLR4) does not bind folic acid or reduced folates. (turkupetcentre.net)
Initiate supplementation with oral folic acid and intramuscular vitamin B 12 to reduce the severity of hematologic and gastrointestinal toxicity of pemetrexed. (nih.gov)
The aims of this study were to assess folate, vitamin B12 and homocysteine status in distinct Brazilian individuals after the initiation of folic acid fortification by Brazilian authorities and to investigate the effects of RFC1 A80G, GCPII C1561T and MTHFR C677T polymorphisms on folate, vitamin B12 and Hcy levels in these populations. (unboundmedicine.com)
Our results suggest that folate deficiency is practically nonexistent in the post-folic acid fortification era in the subgroups evaluated. (unboundmedicine.com)
Drugs such as raltitrexed or methotrexate with structural similarity to folic acid are up to 300-fold more potent inhibitors of WT cultured in a novel low-folate medium, unlike hydrophobic antifols such as trimetrexate or pyrimethamine. (dundee.ac.uk)
This invention involves a series of folate analogs that show selective cytotoxicity toward tumor cells (such as ovarian cancer) that express high levels of the surface protein folate receptor (FR), which binds and transports folic acid and related folates into mammalian cells. (technologypublisher.com)
Vitamin B9, commonly known as folic acid or folate, is a crucial water-soluble B vitamin that plays an essential role in various bodily functions. (healthylivinganswers.com)
Folic acid, the synthetic form of B9, can be found in supplements and fortified foods, while folate occurs naturally in certain foods. (healthylivinganswers.com)
Folate is naturally found in a variety of foods, while folic acid is commonly found in fortified products and supplements. (healthylivinganswers.com)
Adequate folic acid intake before conception and during early pregnancy can significantly reduce the risk of neural tube defects in developing babies. (healthylivinganswers.com)
Therefore, it is recommended that women of childbearing age supplement their diets with folic acid or consume foods rich in folate. (healthylivinganswers.com)
During early pregnancy, folic acid supplementation significantly reduces the risk of neural tube defects in infants. (healthylivinganswers.com)
Many grain products in the United States are also fortified with folic acid to ensure an adequate intake and reduce the risk of neural tube defects. (healthylivinganswers.com)
Folic acid can be obtained from a variety of sources, including natural foods rich in folate and foods fortified with synthetic folic acid. (healthylivinganswers.com)
Checking food labels for the presence of folic acid or folate can help individuals identify fortified products and incorporate them into their diet. (healthylivinganswers.com)
Daily folic acid supplementation was added 1 year later because his plasma folate level was low. (medscape.com)
Periconceptional folic acid intake has been shown to reduce the risk of these outcomes. (cdc.gov)

The Reduced Folate Carrier (RFC) Family (TC 2.A.48) Members of the RFC family mediate the uptake of folate, reduce folate, derivatives of reduced folate and the drug, methotrexate. (nih.gov)
It is conceivable that FRs are useful when folate supply is low or when rapid cell growth requires elevated uptake of folate. (biomedcentral.com)

In this article, we describe a newly discovered disorder called cerebral folate deficiency (CFD) that has recently been closely linked with the general population of children with ASD [7]. (autismfile.com)
Folate deficiency in pregnancy is associated with neural tube defects, restricted fetal growth and fetal programming of diseases later in life. (bepress.com)
There are autosomal recessive disorders associated with mutations in genes encoded for SLC46A1 (hereditary folate malabsorption), FOLR1 (cerebral folate deficiency), SLC19A2 (thiamine-responsive megaloblastic anemia), and SLC19A3 (biotin-responsive basal ganglia disease). (elsevierpure.com)
Cerebral folate transport deficiency results from impaired folate transport across the blood:choroid plexus:cerebrospinal fluid (CSF) barrier. (pediatricneurosciences.com)
We are reporting two children with this treatable cerebral folate transport deficiency. (pediatricneurosciences.com)
T p.R128W, confirming the diagnosis of cerebral folate deficiency. (pediatricneurosciences.com)
In conclusion, cerebral folate transport deficiency should be suspected in every child with global developmental delay, epilepsy, ataxia and neuroimaging showing cerebellar atrophy and calcification. (pediatricneurosciences.com)
Folate deficiency has long been known to be involved in NC defects. (biomedcentral.com)

3] "Isolation of a gene encoding a human reduced folate carrier (RFC1) and analysis of its expression in transport-deficient, methotrexate-resistant human breast cancer cells. (tcdb.org)
8] "Topological and functional analysis of the human reduced folate carrier by hemagglutinin epitope insertion. (tcdb.org)
18] "Topological and functional analysis of the human reduced folate carrier by hemagglutinin epitope insertion. (tcdb.org)

The presence of the MTHFD1 1958G→A, MTHFR (methylenetetrahydrofolate reductase) 1298A→C and RFC-1 (reduced folate carrier 1) 80A→G polymorphisms was investigated by PCR-RFLP methods. (biomedcentral.com)
However, without a properly functioning methylenetetrahydrofolate reductase, MTHFR this conversion cannot take place and folate is not converted to forms that can cross the blood brain barrier. (ncats.io)
Association of methylenetetrahydrofolate reductase polymorphism C677T and dietary folate with the risk of cervical dysplasia. (ncats.io)
Meta-analysis of Methylenetetrahydrofolate reductase maternal gene in Down syndrome: increased susceptibility in women carriers of the MTHFR 677T allele. (cdc.gov)

RFC1 A80G and GCPII C1561T polymorphisms did not affect folate and Hcy levels in the study group. (unboundmedicine.com)
In this investigation, the frequency of common functional polymorphisms in the folate pathway was investigated in a large population-based sample of autism case-parent triads. (phoenixrising.me)
MTHFR A1298C polymorphisms reduce the risk of congenital heart defects: a meta-analysis from 16 case-control studies. (cdc.gov)

The RFC has a lower affinity for folate metabolites, and it lies on both the blood and brain sides as well as in other locations including brain cells. (autismfile.com)
The FRA has a high affinity for the FRA autoantibodies, which block the transport of folate metabolites across this carrier on the blood side. (autismfile.com)
10 Pralatrexate is designed to have a higher affinity for the reduced folate carrier, a protein that is overexpressed in malignant cells and is upregulated by oncogenes. (drugbank.com)
9 Compared to methotrexate, pralatrexate binds to the reduced folate carrier protein-1 (RFC-1) for cellular uptake with 10-times the affinity and is a more potent substrate for FPGS. (drugbank.com)
Among the four isoforms of FRs identified (α, β, γ, and δ), α and β isoforms of FR are glycosylphosphatidylinositol (GPI)-anchored proteins with two N-glycosylation sites, and both have high affinity (K D of approximately 1 nM) for folate [ 2 ]. (biomedcentral.com)
Pralatrexate is a novel antifolate designed to have high affinity for the reduced folate carrier type 1 (RFC-1). (lymphomation.org)
Inhibitory folate analogs show essentially negligible affinity and substrate activity toward the ubiquitously expressed reduced folate carrier (RFC), the major transport system in tissues and tumors. (technologypublisher.com)

RFCs take up folate, reduced folate, derivatives of reduced folate and the drug, methotrexate. (wikipedia.org)
Mammalian cells are devoid of folate biosynthesis and are therefore folate auxotrophs that take up folate vitamins primarily via the reduced folate carrier (RFC). (aspetjournals.org)

CFD is characterized by below normal levels of the active metabolite of folate known as 5-methyltetrahydrofolate (5MTHF) in the central nervous system (CNS), despite normal levels of folate metabolites in the blood. (autismfile.com)

Down-regulation of placental folate transporters in intrauterine growth restriction. (bepress.com)
Fetal folate availability is dependent on maternal folate levels and placental folate transport capacity, mediated by two key transporters, Folate Receptor-α and Reduced Folate Carrier(RFC). (bepress.com)
Multidrug resistance-associated proteins (MRPs) and organic anion transporters (OATs) transport folates in addition to many other substrates, mostly in epithelial tissues. (turkupetcentre.net)
RFC1 is the major target for antifolate drugs in cancer chemotherapy because of its abundance, but antifolates usually target also other folate transporters. (turkupetcentre.net)
Folate transporters are routes of delivery of drugs for the treatment of cancer and inflammatory diseases. (elsevierpure.com)

Pralatrexate is a folate analog metabolic inhibitor that competitively inhibits dihydrofolate reductase (DHFR) selectively in cancer cells overexpressing the reduced folate carrier protein-1 (RFC-1). (drugbank.com)

05). In conclusion, placental folate transport capacity is decreased in IUGR, which may contribute to the restricted fetal growth and intrauterine programming of childhood and adult disease. (bepress.com)

After a multivariate analysis, Hcy levels were predicted by variables such as folate, vitamin B12, gender, age and RFC1 A80G polymorphism, according to the groups studied. (unboundmedicine.com)
A functional polymorphism in the reduced folate carrier gene and DNA hypomethylation in mothers of children with autism. (phoenixrising.me)

The CNS folate receptor protein alpha (FRA) transports 5MTHF directly into the CNS in a process that is dependent on mitochondrial function (ATP production). (autismfile.com)
Folate receptor beta (FRβ) is only detectable in placenta and limited to some hematopoietic cells of myeloid lineage in healthy people. (biomedcentral.com)
Because m909 does not compete with folate for receptor binding, it can be used with folate-drug conjugates in a combination therapy. (biomedcentral.com)
Conjugation of proteins and liposomes to folate does not necessarily prevent the receptor-mediated endocytosis, and this can be utilized in delivery of therapeutic macromolecules into cells ( Leamon and Low, 1991 ). (turkupetcentre.net)
Endocytosis of GPI-linked membrane folate receptor-alpha. (rupress.org)
WSU researchers, in collaboration with Duquesne University, have developed a series of novel folate analogs that show selective toxicity toward tumor cells expressing high levels of the surface protein folate receptor. (technologypublisher.com)

12 Folate is a water-soluble vitamin required for DNA synthesis and maintenance as well as DNA, RNA, and protein methylation. (drugbank.com)
As cancer cells are rapidly replicating, they require a lot of folates to accommodate an accelerated cell division and DNA and protein modification for cellular transformation. (drugbank.com)
The reduced-folate-carrier, an integral membrane protein capable of translocating (anti-)folates across membranes, was completely excluded from the Triton X-100-resistant membrane domains. (rupress.org)

Folate supplementation has been reviewed ( He and Li 2023 ). (tcdb.org)
These findings suggest that continuation of folate supplementation in the second and third trimester is of particular importance in pregnancies complicated by IUGR. (bepress.com)
1.2 Folate Supplementation Safyral is indicated in women who choose to use an oral contraceptive as their method of contraception, to raise folate levels for the purpose of reducing the risk of a neural tube defect in a pregnancy conceived while taking the product or shortly after discontinuing the product. (ncats.io)

Genetic variants of enzymes involved with folate pathway might be expected to have impact on NTD risk. (biomedcentral.com)
Simplified picture showing homocysteine involvement in different metabolic pathways, as well as the role of vitamins B-6, B-12, and folate as a co-factors in this pathway. (medscape.com)

Studies of PCFT-mediated transport, to date, have focused exclusively on the influx of folates and antifolates. (aspetjournals.org)

2] "Isolation of human cDNAs that restore methotrexate sensitivity and reduced folate carrier activity in methotrexate transport-defective Chinese hamster ovary cells. (tcdb.org)
Methotrexate elimination is reduced in patients with impaired renal functions, ascites, or pleural effusions. (nih.gov)

Maternal genetic variants that compromise intrauterine availability of folate derivatives could alter fetal cell trajectories and disrupt normal neurodevelopment. (phoenixrising.me)

Folate hydrolase 1 (FOLH1, PSMA , GCPII) frees folate in the duodenal brush border cells, helping its intestinal absorption. (turkupetcentre.net)

Folates are hydrophilic molecules and anions at physiological pH, and therefore do not diffuse well across cell membranes. (turkupetcentre.net)

Due to its anti-folate activity, pralatrexate's main toxicity is manifested as mucositis that can require dose interruption or reduction 10 , 13 . (drugbank.com)

Vitamin B 9 (pteroylmonoglutamate, PteGlu) is reduced to dihydrofolate and further to tetrahydrofolate (THF). (turkupetcentre.net)
Folate and vitamin B12 are essential nutrients, whose deficiencies are considerable public health problems worldwide, affecting all age groups. (unboundmedicine.com)
Folate, vitamin B12 and Hcy levels were measured by conventional methods. (unboundmedicine.com)
The overall prevalence of folate and vitamin B12 deficiencies were 0.3% and 4.9%, respectively. (unboundmedicine.com)
Folate and vitamin B-12 are required for the remethylation of homocysteine to methionine. (medscape.com)

Folate cofactors are one-carbon donors essential for the biosynthesis of purines and thymidylate. (aspetjournals.org)

SLC19A1 transports folates but not thiamine. (elsevierpure.com)

with those computed via global burden of disease, or by · screening for carriers of common autosomal recessive dis- involving countries in the process of computation to assess orders in the Region, including beta thalassemia and sickle the accuracy of CGD estimates. (who.int)

An HeLa-derived cell line was employed, in which folate-specific transport was mediated exclusively by PCFT. (aspetjournals.org)

Unlike folate-drug conjugates, m909 selectively binds to FRβ, does not recognize FRα, and has at least one effector function. (biomedcentral.com)
Folates are molecules that have a pteridine ring that can be reduced or oxidized, a para-aminobenzoic acid (PABA) linker that together with the pteridine ring binds 1C units, and a variable chain length polyglutamate tail that serves to localize the molecule within the cell. (turkupetcentre.net)

m909 was not only able to select FRβ positive, activated macrophages from synovial fluid cells of arthritis patients as efficiently as folate, but also able to mediate ADCC in FRβ positive cells. (biomedcentral.com)

The Reduced Folate Carrier (RFC) Family (TC# 2.A.48) is a group of transport proteins that is part of the major facilitator superfamily. (wikipedia.org)
The generalized transport reactions catalyzed by the proteins of the RFC family are: Folate derivative (out) + anion (in) ⇌ folate derivative (in) + anion (out) Thiamine (out) + H+ (out) ⇌ thiamine (in) + H+ (in) TPP (in) + H+ (in) ⇌ TPP (out) + H+ (out) Several human RFCs have been linked to chronic kidney disease. (wikipedia.org)

increasing the specificity of folate-based therapeutics aimed for treating inflammation or tumours. (turkupetcentre.net)

Folate:H+ symport, folate:OH−antiport and folate:anion antiport mechanisms have been proposed. (wikipedia.org)
Folate:H+ symport, folate:OH- antiport and folate:anion antiport mechanisms have been proposed, but the energetic mechanism is not well defined. (nih.gov)

5MTHF is also transported into the CNS through the reduced folate carrier (RFC). (autismfile.com)
Impaired transport of 5MTHF into the CNS can lead to reduced levels of 5MTHF in the brain and cause CFD. (autismfile.com)
This leads to low CSF 5-methyltetrahydrofolate (5MTHF), the active folate metabolite. (pediatricneurosciences.com)

Inhibitors of bacterial folate synthesis can be used as antibiotics. (turkupetcentre.net)

The RFC members appear to transport reduced folate by an energy-dependent, pH-dependent, Na+-independent mechanism. (wikipedia.org)
5] "Human intestinal folate transport: cloning, expression, and distribution of complementary RNA. (tcdb.org)
It can transport both reduced and oxidized folates. (turkupetcentre.net)
SLC19A2 and SLC19A3 transport thiamine but not folates. (elsevierpure.com)
In the human body, iron is present in all cells and has several vital functions -- as a carrier of oxygen to the tissues from the lungs in the form of hemoglobin (Hb), as a facilitator of oxygen use and storage in the muscles as myoglobin, as a transport medium for electrons within the cells in the form of cytochromes, and as an integral part of enzyme reactions in various tissues. (cdc.gov)

Rep_2016_EN_18989.pdf?ua=1, accessed 30 March 2017). (who.int)

Intracellular anions are able to promote folate derivative uptake. (wikipedia.org)

Other resistance mechanisms include effl ux pumps, United States, reduced outer membrane permeability, and plasmid-borne genes (e.g., qnr , aac-6-Ib-cr genes) ( 6 , 8 , 10 - 12 ). (cdc.gov)

For people with MTHFR gene variations, supplementing with the already activated form of folate (5-MTHF/5- METHYLTETRAHYDROFOLATE/LEVOMEFOLIC ACID) is far more effective in providing this form of folate than introducing the pre-converted form to the body through typical folate supplements. (ncats.io)

Selective inhibitors of nuclear export block pancreatic cancer cell proliferation and reduce tumor growth in mice. (karmanos.org)

It doesn't specifically mention CFS, but I have found that the methylation and folate related issues in autism are also present in CFS (see www.cfsresearch.org ). (phoenixrising.me)

It may be used as a carrier gas with oxygen in combination with more potent general inhalational gases for surgical anesthesia. (medscape.com)

9 Additionally, pralatrexate also competes for enzymatic processing by folyopolyglutamate synthase (FPGS)with folate to increase cellular retention. (drugbank.com)
Folylpoly-γ-glutamate synthetase (FPGS) catalyzes the addition of multiple glutamates to THF, and is needed for retaining folates intracellularly. (turkupetcentre.net)

Anatomy2

Diseases6

Chemicals and Drugs37

Analytical, Diagnostic and Therapeutic Techniques and Equipment3

Phenomena and Processes6

Information Science2

Health Care1

Metabolism11

Transporter11

Receptors7

Folic21

Uptake of folate2

Deficiency8

Human reduced folate carrier3

Methylenetetrahydrofolate reductase4

Polymorphisms3

Affinity7

Take up folate2

Levels of folate1

Transporters5

Analog metabolic inhibitor1

Placental folate1

Polymorphism2

Receptor6

Protein3

Supplementation3

Pathway2

Antifolates1

Methotrexate2

Derivatives1

Hydrolase1

Membranes1

Toxicity1

Vitamin5

Cofactors1

SLC19A11

Autosomal recessive1

PCFT1

Binds2

Mediate1

Proteins2

Therapeutics1

Anion2

5MTHF3

Synthesis1

Transport5

20171

Derivative1

Genes1

Gene1

Tumor growth1

Methylation1

Potent1

FPGS2