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Identification
- Summary
Levomefolic acid is a folate supplement used to prevent neural tube defects in pregnancy or folate deficiency.
- Brand Names
- Beyaz 28 Day, EnBrace HR, EnLyte, Safyral 28 Day, Tydemy 28 Day, Yaz Plus
- Generic Name
- Levomefolic acid
- DrugBank Accession Number
- DB11256
- Background
Levomefolic acid (INN) is the metabolite of folic acid (Vitamin B9) and it is a predominant active form of folate found in foods and in the blood circulation, accounting for 98% of folates in human plasma 8. It is transported across the membranes including the blood-brain barrier into various tissues where it plays an essential role in the DNA synthesis, cysteine cycle and regulation of homocysteine, where it methylates homocysteine and forms methionine and tetrahydrofolate (THF). Levomefolate is approved as a food additive and is designated a GRAS (generally regarded as safe) compound 13. It is available commercially as a crystalline form of the calcium salt (Metafolin(R)), which has the stability required for use as a supplement 8. Supplementation of levomefolic acid is desired over folic acid due to reduced potential for masking vitamin B12 deficiency symptoms.
- Type
- Small Molecule
- Groups
- Approved, Investigational
- Structure
Structure for Levomefolic acid (DB11256)
- Weight
- Average: 459.4558
Monoisotopic: 459.186631567 - Chemical Formula
- C20H25N7O6
- Synonyms
- (6S)-5-methyltetrahydrofolate
- (6S)-5-Methyltetrahydrofolic acid
- (6S)-5-MTHF
- 5-methyl-(6S)-tetrahydrofolic acid
- L-5-methyltetrahydrofolate
- L-5-MTHF
- L-methylfolate
- Levomefolate
- Levomefolic acid
- LMSR
- N-[4-[[[(6S)-2-Amino-3,4,5,6,7,8-hexahydro-5-methyl-4-oxo-6-pteridinyl]methyl]amino]benzoyl]-L-glutamic acid
Pharmacology
- Indication
For the treatment and prevention of folate deficiency and for use as an antidote against folic acid antagonists. Contained in oral contraceptives to reduce the risk of neural tube defects arising from folic acid deficiency for pregnant women who conceived during use or shortly after the discontinuation of the product. Being studied for use as a treatment for cardiovascular diseases 7 and adjunct therapy for patients undergoing antidepressant pharmacotherapy 5,6.
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- Contraindications & Blackbox Warnings
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Levomefolic acid is an active metabolite of folic acid and a methyl group donor in one-carbon metabolism reactions. It regulates important cellular functions such as DNA biosynthesis, gene expression regulation, amino acid synthesis and metabolism, and myelin synthesis and repair. As a only form of folate that can cross the blood-brain barrier, it acts as a cofactor in the production of monoamine neurotransmitters such as dopamine, serotonin and norepinephrine 6. Levomefolic acid is also involved in red blood cell formation 11.
- Mechanism of action
Levomefolic acid plays a critical role in methylating homocysteines into methionine by acting as a methyl donor in a reaction catalyzed by vitamine B12-dependent methionine synthase. Homocysteine must either be further metabolized via transulfuration to become cysteine, taurine, and glutathione via a B6-dependent process, or re-methylated to become methionine again. Methionine formed from remethylation of homocysteine by levomefolic acid forms the downstream metabolite S-adenosylmethionine (SAMe), which is involved in numerous biochemical methyl donation reactions, including reactions forming monoamine neurotransmitters 10. Studies suggest that high plasma levels of homocysteine is associated with increased incidences of arterial plaque formation 9.
- Absorption
Absorbed in the proximal small intestines via the active proton-coupled folate transporter (PCFT) that transports both oxidized and reduced folic acids. Passive diffusion also occurs at the proximal and distal portions of the small intestines 9. A single oral dose of 906nmol of levomefolic acid in healthy females resulted in the mean peak plasma concentration of 39.4nmol/L 8.
- Volume of distribution
Circulates in its free form or loosely bound to plasma proteins
- Protein binding
Approximately 56% bound to plasma proteins
- Metabolism
Levomefolic acid is further converted into tetrahydrofolate (THF) via the vitamin B12-dependent enzyme methionine synthase before effective polyglutamylation by folylpolyglutamate synthetase (FPG). Polyglumate forms of folic acids are more effective substrates for associated enzymes in folate-dependent reactions.
- Route of elimination
Mainly eliminated through renal or fecal excretion. Small proportion of excreted levomefolic acid is in unchanged form as over 99% of tissue folate is in polyglutamate form. Some portions of levomefolic acid is secreted into bile.
- Half-life
The mean elimination half-life is approximately 3 hours after 5mg of oral L-methylfolate, administered daily for 7 days 15.
- Clearance
Not Available
- Adverse Effects
Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!Improve decision support & research outcomes with our structured adverse effects data.- Toxicity
Overdose of levomefolic acid is unlikely to cause clinically significant adverse events.
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your softwareCapecitabine The risk or severity of adverse effects can be increased when Levomefolic acid is combined with Capecitabine. Carbamazepine The serum concentration of Levomefolic acid can be decreased when it is combined with Carbamazepine. Colestipol The serum concentration of Levomefolic acid can be decreased when it is combined with Colestipol. Flucytosine The risk or severity of adverse effects can be increased when Levomefolic acid is combined with Flucytosine. Fluorouracil The risk or severity of adverse effects can be increased when Levomefolic acid is combined with Fluorouracil. - Food Interactions
- Take with or without food. Recommendations vary from product to product - consult individual product monographs for additional information.
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- Product Ingredients
Ingredient UNII CAS InChI Key Levomefolate calcium A9R10K3F2F 151533-22-1 VWBBRFHSPXRJQD-QNTKWALQSA-L Levomefolate glucosamine Q65PL71Q1A 1181972-37-1 FZDRYCKUVGVDSO-KWWXADPNSA-N Levomefolate magnesium 1VZZ62R081 1429498-11-2 UNKHRTFYDNBUHK-QNTKWALQSA-L - Product Images
- International/Other Brands
- Metafolin
- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image L-Methylfolate Calcium Tablet 15 mg/1 Oral Westminster Pharmaceuticals, LLC 2021-04-09 2024-08-01 US 
L-Methylfolate Calcium Tablet, coated 15 mg/1 Oral Virtus Pharmaceuticals 2015-01-08 Not applicable US L-Methylfolate Calcium Tablet 15 mg/1 Oral Seton Pharmaceuticals 2010-06-30 2012-03-17 US L-Methylfolate Calcium Tablet, coated 15 mg/1 Oral bryant ranch prepack 2015-01-08 Not applicable US L-Methylfolate Calcium Tablet, coated 7.5 mg/1 Oral Virtus Pharmaceuticals 2012-03-15 2015-02-15 US - Mixture Products
Name Ingredients Dosage Route Labeller Marketing Start Marketing End Region Image Beyaz Levomefolate calcium (0.451 mg/1) + Levomefolate calcium (0.451 mg/1) + Drospirenone (3 mg/1) + Ethinylestradiol (0.02 mg/1) Kit; Tablet, film coated Oral Bayer HealthCare Pharmaceuticals Inc. 2010-10-07 Not applicable US 
Beyaz Levomefolate calcium (0.451 mg/1) + Levomefolate calcium (0.451 mg/1) + Drospirenone (3 mg/1) + Ethinylestradiol (0.02 mg/1) Kit; Tablet, film coated Oral Bayer HealthCare Pharmaceuticals Inc. 2010-10-07 Not applicable US Drospirenone, Ethinyl Estradiol and Levomefolate Calcium and Levomefolate Calcium Levomefolate calcium (0.451 mg/1) + Levomefolate calcium (0.451 mg/1) + Drospirenone (3 mg/1) + Ethinylestradiol (0.02 mg/1) Kit; Tablet, film coated Oral Lupin Pharmaceuticals, Inc. 2018-08-22 Not applicable US Drospirenone, Ethinyl Estradiol and Levomefolate Calcium and Levomefolate Calcium Levomefolate calcium (0.451 mg/1) + Levomefolate calcium (0.451 mg/1) + Drospirenone (3 mg/1) + Ethinylestradiol (0.02 mg/1) Kit; Tablet, film coated Oral Lupin Pharmaceuticals, Inc. 2018-08-22 Not applicable US Drospirenone/Ethinyl Estradiol/Levomefolate Calcium and Levomefolate Calcium Levomefolate calcium (0.451 mg/1) + Levomefolate calcium (0.451 mg/1) + Drospirenone (3 mg/1) + Ethinylestradiol (0.02 mg/1) Kit; Tablet, film coated Oral Sandoz Inc 2016-10-12 Not applicable US - Unapproved/Other Products
Name Ingredients Dosage Route Labeller Marketing Start Marketing End Region Image Biopar delta-FORTE Levomefolate magnesium (7 mg/1) + Cobalamin (50 ug/1) + Cobamamide (50 ug/1) + Dihydrofolic Acid (1 mg/1) + Gastric intrinsic factor (50 mg/1) + Levoleucovorin (2.5 mg/1) Capsule Oral Jaymac Pharma 2024-06-01 Not applicable US BumP DHA Levomefolate magnesium (1 mg/1) + Cobamamide (500 mg/1) + Flavin adenine dinucleotide (1 mg/1) + Flavin mononucleotide (2 mg/1) + Iron (15 mg/1) + Leucovorin (1 mg/1) + Magnesium oxide (125 mg/1) + NADH (25 ug/1) + Omega-3 fatty acids (300 mg/1) + Potassium Iodide (250 ug/1) + Pyridoxal phosphate (5 mg/1) + Pyridoxine hydrochloride (20 mg/1) + Zinc glycinate (15 1/1) Capsule Oral Centurion Labs 2017-03-24 2017-04-17 US Chromagen Levomefolic acid (750 ug/1) + Ascorbic acid (60 mg/1) + Cyanocobalamin (10 ug/1) + Ferrous asparto glycinate (25 mg/1) + Ferrous fumarate (50 mg/1) + Folic acid (250 ug/1) + Gastric intrinsic factor (100 mg/1) + Zinc (12 mg/1) Capsule Oral Avion Pharmaceuticals, Llc 2017-01-10 Not applicable US Davimet with Fluoride Levomefolate calcium (1000 ug/1) + Ascorbic acid (24 mg/1) + Cholecalciferol (10 ug/1) + DL-alpha tocopheryl acetate (6.75 mg/1) + Mecobalamin (4.5 ug/1) + Niacin (13.5 mg/1) + Pyridoxine hydrochloride (1.05 mg/1) + Riboflavin (1.2 mg/1) + Sodium ascorbate (36 mg/1) + Sodium fluoride (0.75 mg/1) + Thiamine mononitrate (1.05 mg/1) + Vitamin A (750 ug/1) Tablet, chewable Oral PureTek Corporation 2024-02-28 Not applicable US Davimet with Iron Levomefolate calcium (1000 ug/1) + Ascorbic acid (24 mg/1) + Cholecalciferol (10 ug/1) + DL-alpha tocopheryl acetate (6.75 mg/1) + Iron (11 mg/1) + Mecobalamin (4.5 ug/1) + Nicotinamide (13.5 mg/1) + Pyridoxine hydrochloride (1.05 mg/1) + Riboflavin (1.2 mg/1) + Sodium ascorbate (36 mg/1) + Thiamine mononitrate (1.05 mg/1) + Vitamin A acetate (750 ug/1) Tablet Oral PureTek Corporation 2024-06-03 Not applicable US
Categories
- Drug Categories
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as tetrahydrofolic acids. These are heterocyclic compounds based on the 5,6,7,8-tetrahydropteroic acid skeleton conjugated with at least one L-glutamic acid unit.
- Kingdom
- Organic compounds
- Super Class
- Organoheterocyclic compounds
- Class
- Pteridines and derivatives
- Sub Class
- Pterins and derivatives
- Direct Parent
- Tetrahydrofolic acids
- Alternative Parents
- Glutamic acid and derivatives / N-acyl-alpha amino acids / Hippuric acids / Aminobenzamides / Aniline and substituted anilines / Phenylalkylamines / Benzoyl derivatives / Dialkylarylamines / Aminopyrimidines and derivatives / Secondary alkylarylamines show 13 more
- Substituents
- Alpha-amino acid or derivatives / Amine / Amino acid / Amino acid or derivatives / Aminobenzamide / Aminobenzoic acid or derivatives / Aminopyrimidine / Aniline or substituted anilines / Aromatic heteropolycyclic compound / Azacycle show 35 more
- Molecular Framework
- Aromatic heteropolycyclic compounds
- External Descriptors
- tetrahydrofolic acid (CHEBI:15641)
- Affected organisms
- Not Available
Chemical Identifiers
- UNII
- 8S95DH25XC
- CAS number
- 31690-09-2
- InChI Key
- ZNOVTXRBGFNYRX-STQMWFEESA-N
- InChI
- InChI=1S/C20H25N7O6/c1-27-12(9-23-16-15(27)18(31)26-20(21)25-16)8-22-11-4-2-10(3-5-11)17(30)24-13(19(32)33)6-7-14(28)29/h2-5,12-13,22H,6-9H2,1H3,(H,24,30)(H,28,29)(H,32,33)(H4,21,23,25,26,31)/t12-,13-/m0/s1
- IUPAC Name
- (2S)-2-{[4-({[(6S)-2-amino-5-methyl-4-oxo-1,4,5,6,7,8-hexahydropteridin-6-yl]methyl}amino)phenyl]formamido}pentanedioic acid
- SMILES
- CN1[C@@H](CNC2=CC=C(C=C2)C(=O)N[C@@H](CCC(O)=O)C(O)=O)CNC2=C1C(=O)N=C(N)N2
References
- General References
- Fruzzetti F: Beyaz(R): an oral contraceptive fortified with folate. Womens Health (Lond). 2012 Jan;8(1):13-9. doi: 10.2217/whe.11.68. [Article]
- Bart S Sr, Marr J, Diefenbach K, Trummer D, Sampson-Landers C: Folate status and homocysteine levels during a 24-week oral administration of a folate-containing oral contraceptive: a randomized, double-blind, active-controlled, parallel-group, US-based multicenter study. Contraception. 2012 Jan;85(1):42-50. doi: 10.1016/j.contraception.2011.05.013. Epub 2011 Jul 13. [Article]
- Rapkin RB, Creinin MD: The combined oral contraceptive pill containing drospirenone and ethinyl estradiol plus levomefolate calcium. Expert Opin Pharmacother. 2011 Oct;12(15):2403-10. doi: 10.1517/14656566.2011.610791. Epub 2011 Aug 31. [Article]
- Wilson SM, Bivins BN, Russell KA, Bailey LB: Oral contraceptive use: impact on folate, vitamin B(6), and vitamin B(1)(2) status. Nutr Rev. 2011 Oct;69(10):572-83. doi: 10.1111/j.1753-4887.2011.00419.x. [Article]
- Ginsberg LD, Oubre AY, Daoud YA: L-methylfolate Plus SSRI or SNRI from Treatment Initiation Compared to SSRI or SNRI Monotherapy in a Major Depressive Episode. Innov Clin Neurosci. 2011 Jan;8(1):19-28. [Article]
- Shelton RC, Sloan Manning J, Barrentine LW, Tipa EV: Assessing Effects of l-Methylfolate in Depression Management: Results of a Real-World Patient Experience Trial. Prim Care Companion CNS Disord. 2013;15(4). pii: PCC.13m01520. doi: 10.4088/PCC.13m01520. Epub 2013 Aug 29. [Article]
- Willems FF, Boers GH, Blom HJ, Aengevaeren WR, Verheugt FW: Pharmacokinetic study on the utilisation of 5-methyltetrahydrofolate and folic acid in patients with coronary artery disease. Br J Pharmacol. 2004 Mar;141(5):825-30. Epub 2004 Feb 9. [Article]
- Pietrzik K, Bailey L, Shane B: Folic acid and L-5-methyltetrahydrofolate: comparison of clinical pharmacokinetics and pharmacodynamics. Clin Pharmacokinet. 2010 Aug;49(8):535-48. doi: 10.2165/11532990-000000000-00000. [Article]
- Miraglia N, Agostinetto M, Bianchi D, Valoti E: Enhanced oral bioavailability of a novel folate salt: comparison with folic acid and a calcium folate salt in a pharmacokinetic study in rats. Minerva Ginecol. 2016 Apr;68(2):99-105. [Article]
- Miller AL: The methylation, neurotransmitter, and antioxidant connections between folate and depression. Altern Med Rev. 2008 Sep;13(3):216-26. [Article]
- Lamers Y, Prinz-Langenohl R, Bramswig S, Pietrzik K: Red blood cell folate concentrations increase more after supplementation with [6S]-5-methyltetrahydrofolate than with folic acid in women of childbearing age. Am J Clin Nutr. 2006 Jul;84(1):156-61. [Article]
- Dailymed [Link]
- FDA Center for Drug Evaluation and Research: Summary Review [Link]
- Cayman Chemicals Safety Data Sheet [Link]
- Dailymed L-Methyl-MC-NAC Tablets [Link]
- External Links
- KEGG Compound
- C00440
- PubChem Compound
- 444412
- PubChem Substance
- 347827954
- ChemSpider
- 392351
- BindingDB
- 50391007
- 1025342
- ChEBI
- 136009
- ChEMBL
- CHEMBL1231574
- ZINC
- ZINC000002005305
- PharmGKB
- PA166129561
- PDBe Ligand
- THH
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Levomefolic_acid
- PDB Entries
- 1b02 / 1q8j / 1tls / 1tsn / 1u1j / 1wsv / 1xpg / 1xr2 / 1zp4 / 2e7f … show 27 more
- MSDS
- Download (51 KB)
Clinical Trials
- Clinical Trials
Clinical Trial & Rare Diseases Add-on Data Package
Explore 4,000+ rare diseases, orphan drugs & condition pairs, clinical trial why stopped data, & more. Preview package Phase Status Purpose Conditions Count Start Date Why Stopped 100+ additional columns Unlock 175K+ rows when you subscribe.View sample data4 Completed Treatment Polycystic Ovarian Syndrome (PCOS) 1 somestatus stop reason just information to hide 4 Not Yet Recruiting Other Generalized Anxiety Disorder 1 somestatus stop reason just information to hide 4 Recruiting Treatment Acute Diarrhea 1 somestatus stop reason just information to hide 4 Recruiting Treatment Iron Deficiency Anemia of Pregnancy / Iron Storage Disease 1 somestatus stop reason just information to hide 4 Terminated Treatment Anemia 1 somestatus stop reason just information to hide
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Kit; tablet, film coated Oral Capsule Oral 15 mg/1 Capsule, delayed release pellets Oral Solution / drops Oral Tablet Oral Tablet Oral 15 mg/1 Tablet Oral 7.5 mg/1 Tablet, coated Oral 15 mg/1 Tablet, coated Oral 7.5 mg/1 Tablet, coated Oral Capsule Oral Capsule, liquid filled; kit; tablet Oral Capsule, liquid filled; kit; tablet, film coated Oral Suspension / drops Oral Kit Oral Tablet, film coated Oral Capsule, gelatin coated Oral Liquid Oral Capsule, liquid filled Oral Tablet, chewable Oral Capsule; kit; tablet, coated Oral Powder Oral; Topical Powder Oral - Prices
- Not Available
- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US7163931 No 2007-01-16 2021-12-20 US US6958326 No 2005-10-25 2021-12-20 US US5798338 No 1998-08-25 2015-07-10 US US6441168 No 2002-08-27 2022-07-30 US US8617597 No 2013-12-31 2030-02-08 US US11617751 No 2010-07-17 2030-07-17 US
Properties
- State
- Solid
- Experimental Properties
Property Value Source boiling point (°C) 221 MSDS water solubility Approximately 0.3 mg/ml Cayman Chemical Safety Data Sheet - Predicted Properties
Property Value Source Water Solubility 0.332 mg/mL ALOGPS logP -0.58 ALOGPS logP -3 Chemaxon logS -3.1 ALOGPS pKa (Strongest Acidic) 3.23 Chemaxon pKa (Strongest Basic) 5.32 Chemaxon Physiological Charge -2 Chemaxon Hydrogen Acceptor Count 12 Chemaxon Hydrogen Donor Count 7 Chemaxon Polar Surface Area 198.48 Å2 Chemaxon Rotatable Bond Count 9 Chemaxon Refractivity 126.68 m3·mol-1 Chemaxon Polarizability 46.56 Å3 Chemaxon Number of Rings 3 Chemaxon Bioavailability 0 Chemaxon Rule of Five No Chemaxon Ghose Filter No Chemaxon Veber's Rule No Chemaxon MDDR-like Rule Yes Chemaxon - Predicted ADMET Features
- Not Available
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS splash10-03di-0209000000-bc39a561e34ef2dd829c Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS splash10-0a4i-0002900000-9f11e687468c9cb33847 Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS splash10-03di-0209100000-57a17001eef7ce551306 Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS splash10-0ue9-1904300000-971d324927f268b4a519 Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS splash10-001i-0913000000-2ac627a3103a392beb1c Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS splash10-0uxu-3837900000-71bc9ab44596b01eeedd Predicted 1H NMR Spectrum 1D NMR Not Applicable Predicted 13C NMR Spectrum 1D NMR Not Applicable - Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 243.4135067 predictedDarkChem Lite v0.1.0 [M-H]- 243.3961067 predictedDarkChem Lite v0.1.0 [M-H]- 193.82654 predictedDeepCCS 1.0 (2019) [M+H]+ 243.5589067 predictedDarkChem Lite v0.1.0 [M+H]+ 243.3271067 predictedDarkChem Lite v0.1.0 [M+H]+ 196.2221 predictedDeepCCS 1.0 (2019) [M+Na]+ 242.9517067 predictedDarkChem Lite v0.1.0 [M+Na]+ 242.7082067 predictedDarkChem Lite v0.1.0 [M+Na]+ 202.13463 predictedDeepCCS 1.0 (2019)
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- SubstrateCofactor
- General Function
- Catalyzes the transfer of a methyl group from methylcob(III)alamin (MeCbl) to homocysteine, yielding enzyme-bound cob(I)alamin and methionine in the cytosol (PubMed:16769880, PubMed:17288554, PubMed:27771510). MeCbl is an active form of cobalamin (vitamin B12) used as a cofactor for methionine biosynthesis. Cob(I)alamin form is regenerated to MeCbl by a transfer of a methyl group from 5-methyltetrahydrofolate (PubMed:16769880, PubMed:17288554, PubMed:27771510). The processing of cobalamin in the cytosol occurs in a multiprotein complex composed of at least MMACHC, MMADHC, MTRR (methionine synthase reductase) and MTR which may contribute to shuttle safely and efficiently cobalamin towards MTR in order to produce methionine (PubMed:16769880, PubMed:27771510)
- Specific Function
- Cobalamin binding
- Gene Name
- MTR
- Uniprot ID
- Q99707
- Uniprot Name
- Methionine synthase
- Molecular Weight
- 140525.91 Da
References
- Pietrzik K, Bailey L, Shane B: Folic acid and L-5-methyltetrahydrofolate: comparison of clinical pharmacokinetics and pharmacodynamics. Clin Pharmacokinet. 2010 Aug;49(8):535-48. doi: 10.2165/11532990-000000000-00000. [Article]
Transporters
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Proton-coupled folate symporter that mediates folate absorption using an H(+) gradient as a driving force (PubMed:17129779, PubMed:17446347, PubMed:17475902, PubMed:19389703, PubMed:19762432, PubMed:25504888, PubMed:29344585, PubMed:30858177, PubMed:31494288, PubMed:31792273, PubMed:32893190, PubMed:34619546). Involved in the intestinal absorption of folates at the brush-border membrane of the proximal jejunum, and the transport from blood to cerebrospinal fluid across the choroid plexus (PubMed:17129779, PubMed:17446347, PubMed:17475902, PubMed:19389703, PubMed:25504888, PubMed:29344585, PubMed:30858177, PubMed:31494288, PubMed:32893190). Functions at acidic pH via alternate outward- and inward-open conformation states (PubMed:32893190, PubMed:34040256). Protonation of residues in the outward open state primes the protein for transport (PubMed:34040256). Binding of folate promotes breaking of salt bridge network and subsequent closure of the extracellular gate, leading to the inward-open state and release of protons and folate (PubMed:34040256). Also able to transport antifolate drugs, such as methotrexate and pemetrexed, which are established treatments for cancer and autoimmune diseases (PubMed:18524888, PubMed:19762432, PubMed:22345511, PubMed:25608532, PubMed:28802835, PubMed:29326243, PubMed:34040256, PubMed:34619546). Involved in FOLR1-mediated endocytosis by serving as a route of export of folates from acidified endosomes (PubMed:19074442). Also acts as a lower-affinity, pH-independent heme carrier protein and constitutes the main importer of heme in the intestine (PubMed:17156779). Imports heme in the retina and retinal pigment epithelium, in neurons of the hippocampus, in hepatocytes and in the renal epithelial cells (PubMed:32621820). Hence, participates in the trafficking of heme and increases intracellular iron content (PubMed:32621820)
- Specific Function
- Folic acid binding
- Gene Name
- SLC46A1
- Uniprot ID
- Q96NT5
- Uniprot Name
- Proton-coupled folate transporter
- Molecular Weight
- 49770.04 Da
References
- Zhao R, Aluri S, Goldman ID: The proton-coupled folate transporter (PCFT-SLC46A1) and the syndrome of systemic and cerebral folate deficiency of infancy: Hereditary folate malabsorption. Mol Aspects Med. 2017 Feb;53:57-72. doi: 10.1016/j.mam.2016.09.002. Epub 2016 Sep 21. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Antiporter that mediates the import of reduced folates or a subset of cyclic dinucleotides, driven by the export of organic anions (PubMed:10787414, PubMed:15337749, PubMed:16115875, PubMed:22554803, PubMed:31126740, PubMed:31511694, PubMed:32276275, PubMed:7826387, PubMed:9041240). Mechanistically, acts as a secondary active transporter, which exports intracellular organic anions down their concentration gradients to facilitate the uptake of its substrates (PubMed:22554803, PubMed:31126740, PubMed:31511694). Has high affinity for N5-methyltetrahydrofolate, the predominant circulating form of folate (PubMed:10787414, PubMed:14609557, PubMed:22554803). Also able to mediate the import of antifolate drug methotrexate (PubMed:22554803, PubMed:7615551, PubMed:7641195, PubMed:9767079). Also acts as an importer of immunoreactive cyclic dinucleotides, such as cyclic GMP-AMP (2'-3'-cGAMP), an immune messenger produced in response to DNA virus in the cytosol, and its linkage isomer 3'-3'-cGAMP, thus playing a role in triggering larger immune responses (PubMed:31126740, PubMed:31511694, PubMed:36745868). 5-amino-4-imidazolecarboxamide riboside (AICAR), when phosphorylated to AICAR monophosphate, can serve as an organic anion for antiporter activity (PubMed:22554803)
- Specific Function
- 2',3'-cyclic gmp-amp binding
- Gene Name
- SLC19A1
- Uniprot ID
- P41440
- Uniprot Name
- Reduced folate transporter
- Molecular Weight
- 64867.62 Da
References
- Hou Z, Matherly LH: Biology of the major facilitative folate transporters SLC19A1 and SLC46A1. Curr Top Membr. 2014;73:175-204. doi: 10.1016/B978-0-12-800223-0.00004-9. [Article]
Drug created at December 03, 2015 16:51 / Updated at June 02, 2024 21:55