Folic acid
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Identification
- Summary
Folic acid is a nutrient used to treat megaloblastic anemia and is found in many supplements.
- Brand Names
- Animi-3 With Vitamin D, Citranatal B-calm Kit, Citranatal Harmony, Concept Ob, EnBrace HR, EnLyte, Ferralet 90, Folbic, Foltabs, Hematogen, Infuvite, Infuvite Pediatric, Irospan 24/6 Kit, Magnebind 400 Rx, Mvc-fluoride, Mvi Pediatric, Natafort, Nicomide, Pregvit, Tandem Plus, Vitafol-one
- Generic Name
- Folic acid
- DrugBank Accession Number
- DB00158
- Background
Folic acid, also known as folate or Vitamin B9, is a member of the B vitamin family and an essential cofactor for enzymes involved in DNA and RNA synthesis. More specifically, folic acid is required by the body for the synthesis of purines, pyrimidines, and methionine before incorporation into DNA or protein. Folic acid is particularly important during phases of rapid cell division, such as infancy, pregnancy, and erythropoiesis, and plays a protective factor in the development of cancer. As humans are unable to synthesize folic acid endogenously, diet and supplementation is necessary to prevent deficiencies. For example, folic acid is present in green vegetables, beans, avocado, and some fruits.9
In order to function within the body, folic acid must first be reduced by the enzyme dihydrofolate reductase (DHFR) into the cofactors dihydrofolate (DHF) and tetrahydrofolate (THF). This important pathway, which is required for de novo synthesis of nucleic acids and amino acids, is disrupted by anti-metabolite therapies such as Methotrexate as they function as DHFR inhibitors to prevent DNA synthesis in rapidly dividing cells, and therefore prevent the formation of DHF and THF. When used in high doses such as for cancer therapy, or in low doses such as for Rheumatoid Arthritis or psoriasis, Methotrexate impedes the body's ability to create folic acid. This results in a deficiency of coenzymes and a resultant buildup of toxic substances that are responsible for numerous adverse side effects. As a result, supplementation with 1-5mg of folic acid is recommended to prevent deficiency and a number of side effects associated with MTX therapy including mouth ulcers and gastrointestinal irritation. Leucovorin (also known as folinic acid) supplementation is typically used for high-dose MTX regimens for the treatment of cancer. Levoleucovorin and leucovorin are analogs of tetrahydrofolate (THF) and are able to bypass DHFR reduction to act as a cellular replacement for the co-factor THF.
There are also several antiepileptic drugs (AEDs) that are associated with reduced serum and red blood cell folate, including Carbamazepine (CBZ), Phenytoin (PHT), or barbiturates.7 Folic acid is therefore often provided as supplementation to individuals using these medications, particularly to women of child-bearing age.
Inadequate folate levels can result in a number of health concerns including cardiovascular disease, megaloblastic anemias, cognitive deficiencies, and neural tube defects (NTDs). Folic acid is typically supplemented during pregnancy to prevent the development of NTDs and in individuals with alcoholism to prevent the development of neurological disorders, for example.
- Type
- Small Molecule
- Groups
- Approved, Nutraceutical, Vet approved
- Structure
- Weight
- Average: 441.3975
Monoisotopic: 441.139681375 - Chemical Formula
- C19H19N7O6
- Synonyms
- Acide folique
- ácido fólico
- Acidum folicum
- Folacin
- Folate
- Folic acid
- Folsäure
- N-[(4-{[(2-amino-4-oxo-1,4-dihydropteridin-6-yl)methyl]amino}phenyl)carbonyl]-L-glutamic acid
- N-pteroyl-L-glutamic acid
- PGA
- PteGlu
- Pteroyl-L-glutamate
- Pteroyl-L-glutamic acid
- Pteroyl-L-monoglutamic acid
- Pteroylglutamic acid
- Vitamin B9
- Vitamin Bc
- Vitamin M
- External IDs
- NSC-3073
Pharmacology
- Indication
Folic acid is indicated for the treatment of folic acid deficiency, megaloblastic anemia, and in anemias of nutritional origins, pregnancy, infancy, or childhood.
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Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Used in combination to treat Anaemia folate deficiency Combination Product in combination with: Ferrous sulfate anhydrous (DB13257) •••••••••••• ••••••• ••••••• ••••••• •••••••• ••••••• Used in combination to prevent Anaemia folate deficiency Combination Product in combination with: Ferrous sulfate anhydrous (DB13257) •••••••••••• ••••••• ••••••• ••••••• •••••••• ••••••• Used in combination to treat Folate deficiency Combination Product in combination with: Ferrous sulfate anhydrous (DB13257) •••••••••••• ••••••••••••• ••••••• ••••••• ••••••• •••••••• ••••••• Used in combination to treat Folate deficiency Combination Product in combination with: Ferrous sulfate anhydrous (DB13257) •••••••••••• ••••••••• ••••••• ••••••• ••••••• •••••••• ••••••• Used in combination to treat Folate deficiency Combination Product in combination with: Ferrous sulfate anhydrous (DB13257) •••••••••••• •••••••••• ••••• ••••••• ••••••• ••••••• •••••••• ••••••• - Associated Therapies
- Contraindications & Blackbox Warnings
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- Pharmacodynamics
Folic acid is a water-soluble B-complex vitamin found in foods such as liver, kidney, yeast, and leafy, green vegetables. Also known as folate or Vitamin B9, folic acid is an essential cofactor for enzymes involved in DNA and RNA synthesis. More specifically, folic acid is required by the body for the synthesis of purines, pyrimidines, and methionine before incorporation into DNA or protein. Folic acid is the precursor of tetrahydrofolic acid, which is involved as a cofactor for transformylation reactions in the biosynthesis of purines and thymidylates of nucleic acids. Impairment of thymidylate synthesis in patients with folic acid deficiency is thought to account for the defective deoxyribonucleic acid (DNA) synthesis that leads to megaloblast formation and megaloblastic and macrocytic anemias. Folic acid is particularly important during phases of rapid cell division, such as infancy, pregnancy, and erythropoiesis, and plays a protective factor in the development of cancer. As humans are unable to synthesize folic acid endogenously, diet and supplementation is necessary to prevent deficiencies. In order to function properly within the body, folic acid must first be reduced by the enzyme dihydrofolate reductase (DHFR) into the cofactors dihydrofolate (DHF) and tetrahydrofolate (THF). This important pathway, which is required for de novo synthesis of nucleic acids and amino acids, is disrupted by anti-metabolite therapies such as Methotrexate as they function as DHFR inhibitors to prevent DNA synthesis in rapidly dividing cells, and therefore prevent the formation of DHF and THF.
In general, folate serum levels below 5 ng/mL indicate folate deficiency, and levels below 2 ng/mL usually result in megaloblastic anemia.
- Mechanism of action
Folic acid, as it is biochemically inactive, is converted to tetrahydrofolic acid and methyltetrahydrofolate by dihydrofolate reductase (DHFR). These folic acid congeners are transported across cells by receptor-mediated endocytosis where they are needed to maintain normal erythropoiesis, synthesize purine and thymidylate nucleic acids, interconvert amino acids, methylate tRNA, and generate and use formate. Using vitamin B12 as a cofactor, folic acid can normalize high homocysteine levels by remethylation of homocysteine to methionine via methionine synthetase.
Target Actions Organism AProton-coupled folate transporter modulatorHumans AReduced folate transporter modulatorHumans UFolate receptor gamma binderHumans UFolate receptor beta binderHumans UFolate receptor alpha Not Available Humans - Absorption
Folic acid is absorbed rapidly from the small intestine, primarily from the proximal portion. Naturally occurring conjugated folates are reduced enzymatically to folic acid in the gastrointestinal tract prior to absorption. Folic acid appears in the plasma approximately 15 to 30 minutes after an oral dose; peak levels are generally reached within 1 hour.Label
- Volume of distribution
Tetrahydrofolic acid derivatives are distributed to all body tissues but are stored primarily in the liver.
- Protein binding
Very high to plasma protein
- Metabolism
Folic acid is metabolized in the liver into the cofactors dihydrofolate (DHF) and tetrahydrofolate (THF) by the enzyme dihydrofolate reductase (DHFR).
Hover over products below to view reaction partners
- Route of elimination
After a single oral dose of 100 mcg of folic acid in a limited number of normal adults, only a trace amount of the drug appeared in the urine. An oral dose of 5 mg in 1 study and a dose of 40 mcg/kg of body weight in another study resulted in approximately 50% of the dose appearing in the urine. After a single oral dose of 15 mg, up to 90% of the dose was recovered in the urine. A majority of the metabolic products appeared in the urine after 6 hours; excretion was generally complete within 24 hours. Small amounts of orally administered folic acid have also been recovered in the feces. Folic acid is also excreted in the milk of lactating mothers.
- Half-life
Not Available
- Clearance
Not Available
- Adverse Effects
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- Toxicity
IPR-MUS LD50 85 mg/kg,IVN-GPG LD50 120 mg/kg, IVN-MUS LD50 239 mg/kg, IVN-RAT LD50 500 mg/kg, IVN-RBT LD50 410 mg/kg
- Pathways
Pathway Category Methylenetetrahydrofolate Reductase Deficiency (MTHFRD) Disease Folate Metabolism Metabolic Methotrexate Action Pathway Drug action Folate Malabsorption, Hereditary Disease - 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 softwareAbacavir Folic acid may decrease the excretion rate of Abacavir which could result in a higher serum level. Abemaciclib Abemaciclib may decrease the excretion rate of Folic acid which could result in a higher serum level. Acamprosate The excretion of Acamprosate can be decreased when combined with Folic acid. Aceclofenac Aceclofenac may decrease the excretion rate of Folic acid which could result in a higher serum level. Acemetacin Acemetacin may decrease the excretion rate of Folic acid which could result in a higher serum level. - Food Interactions
- No interactions found.
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 Folate sodium 9P9W8GGU78 6484-89-5 SWIRFWUEJODNRG-CURYUGHLSA-L - Product Images
- International/Other Brands
- Acfol (Cazi) / Fefol (GlaxoSmithKline)
- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Acide Folique 5 Tab Tablet 5 mg Oral Pro Doc Limitee 1982-12-31 2010-07-13 Canada Folic Acid Tablet 5 mg Oral Aa Pharma Inc 1978-12-31 Not applicable Canada Folic Acid Tablet 1 mg/1 Oral West Ward Pharmaceutical 2007-05-28 Not applicable US Folic Acid Tablet 1 mg/1 Oral Mutual Pharmaceutical 2006-09-20 Not applicable US Folic Acid Tablet 1 mg/1 Oral Apace Packaging 2009-12-23 Not applicable US - Generic Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Folic Acid Tablet 1 mg/1 Oral Nucare Pharmaceuticals,inc. 2022-03-07 Not applicable US Folic Acid Tablet 1 mg/1 Oral Proficient Rx LP 2009-01-12 Not applicable US Folic Acid Tablet 1 mg/1 Oral PD-Rx Pharmaceuticals, Inc. 2015-08-04 Not applicable US Folic Acid Tablet 1 mg/1 Oral Safecor Health, LLC 2014-09-30 2019-11-11 US Folic Acid Tablet 1 mg/1 Oral Cadila Pharmaceuticals Limited 2018-11-20 Not applicable US - Over the Counter Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image APPETON ESSENTIALS FOLIC ACID TABLET Tablet 400 mcg Oral KOTRA PHARMA (M) SDN. BHD. 2020-09-08 Not applicable Malaysia AXCEL FOLIC ACID TABLET Tablet 5 mg Oral KOTRA PHARMA (M) SDN. BHD. 2020-09-08 Not applicable Malaysia Duafolic 5mg Tablet Tablet 5 mg Oral DUOPHARMA MANUFACTURING (BANGI) SDN. BHD. 2020-09-08 Not applicable Malaysia F - MIN Tablet 5 mg Oral บริษัท พาตาร์แลบ (2517) จำกัด จำกัด 2014-05-08 Not applicable Thailand Folic Acid Capsule 1 mg / cap Oral Sisu Inc. 1999-08-03 2006-07-31 Canada - Mixture Products
Name Ingredients Dosage Route Labeller Marketing Start Marketing End Region Image 24 Multivitamins + Minerals Folic acid (.8 mg) + Ascorbic acid (150 mg) + Beta carotene (10000 unit) + Biotin (25 mcg) + Calcium (130 mg) + Cholecalciferol (400 unit) + Choline bitartrate (25 mg) + Chromium (20 mcg) + Copper (1 mg) + Cyanocobalamin (25 mcg) + Ferrous fumarate (15 mg) + Inositol (25 mg) + Magnesium (65 mg) + Manganese cation (2 mg) + Molybdenum (20 mcg) + Niacin (25 mg) + Calcium pantothenate (25 mg) + Potassium (15 mg) + Potassium Iodide (.1 mg) + Pyridoxine hydrochloride (25 mg) + Racemethionine (25 mg) + Riboflavin (25 mg) + Selenium (20 mcg) + Thiamine hydrochloride (25 mg) + Vanadium (20 mcg) + Vitamin A palmitate (5000 unit) + Vitamin E (50 unit) + Zinc (10 mg) Tablet Oral Stanley Pharmaceuticals, A Division Of Vita Health Products Inc. 1997-04-30 2002-07-31 Canada 4Life Targeted Vitamin & Mineral Complex Capsule Folic acid (0.1 mg) + Ascorbic acid (50.76 mg) + Beta carotene (630 IU) + Chromium (0.07 mg) + Copper (0.5 mg) + Cyanocobalamin (0.002 mg) + Magnesium (46.4 mg) + Niacin (5 mg) + Potassium (12.5 mg) + Pyridoxine (0.5 mg) + Selenium (0.013 mg) + Vanadium (0.15 mg) + Vitamin E (25.5 IU) + Zinc (2.5 mg) Capsule Oral Forlife Research Imports Sdn. Bhd. 2020-09-08 Not applicable Malaysia 50 Plus Folic acid (.2 mg) + Ascorbic acid (200 mg) + Biotin (20 mcg) + Choline bitartrate (20 mg) + Cyanocobalamin (20 mcg) + Inositol (20 mg) + Niacin (20 mg) + Calcium pantothenate (20 mg) + Pyridoxine hydrochloride (20 mg) + Racemethionine (20 mg) + Riboflavin (20 mg) + Thiamine hydrochloride (20 mg) + Vitamin A palmitate (10000 unit) + Vitamin D (400 unit) + Vitamin E (20 unit) Tablet Oral Quest Vitamins A Div Of Purity Life Health Products 1998-08-04 2001-07-06 Canada 50 Plus Multiple Vitamins & Minerals Folic acid (0.4 mg) + Ascorbic acid (90 mg) + Biotin (45 mcg) + Calcium (200 mg) + Cholecalciferol (400 unit) + Chromium (10 mcg) + Copper (2 mg) + Cyanocobalamin (25 mcg) + Magnesium (100 mg) + Manganese cation (5 mg) + Molybdenum (25 mcg) + Nicotinamide (40 mg) + Pantothenic acid (10 mg) + Potassium Iodide (0.15 mg) + Pyridoxine hydrochloride (3 mg) + Riboflavin (3.2 mg) + Selenium (25 mcg) + Thiamine mononitrate (2.25 mg) + Vanadium (10 mcg) + Vitamin A palmitate (6000 unit) + Zinc (15 mg) Tablet Oral Gfr Pharma Ltd. 2002-10-20 2004-06-15 Canada A.R.T.H. Away Formula Folic acid (0.025 mg) + Calcium (24 mg) + Cholecalciferol (45 unit) + Copper (0.232 mg) + Manganese cation (0.58 mg) + Pyridoxine hydrochloride (0.5 mg) + Selenium (1.54 mcg) + Zinc (0.63 mg) Capsule Oral Abundance Naturally Ltd 1999-02-01 2006-06-16 Canada - Unapproved/Other Products
Name Ingredients Dosage Route Labeller Marketing Start Marketing End Region Image Abavite Folic acid (1 mg/1) + Ascorbic acid (60 mg/1) + Cholecalciferol (0.025 mg/1) + DL-alpha tocopheryl acetate (13.5 mg/1) + Ferrous sulfate (30 mg/1) + Magnesium oxide (25 mg/1) + Mecobalamin (0.5 mg/1) + Niacin (15 mg/1) + Calcium pantothenate (5 mg/1) + Potassium Iodide (0.25 mg/1) + Riboflavin (1.8 mg/1) + Thiamine mononitrate (1.6 mg/1) + Vitamin A palmitate (0.33 mg/1) + Zinc oxide (15 mg/1) Tablet Oral ABACOS HEALTH 2021-03-31 Not applicable US Active FE Folic acid (1250 ug/1) + Ascorbic acid (160 mg/1) + Beta carotene (2100 [iU]/1) + Cholecalciferol (400 [iU]/1) + Cupric oxide (1 mg/1) + Cyanocobalamin (30 ug/1) + DL-alpha tocopheryl acetate (40 [iU]/1) + Iron (75 mg/1) + Magnesium oxide (30 mg/1) + Nicotinamide (20 mg/1) + Pyridoxine hydrochloride (20 mg/1) + Riboflavin (4 mg/1) + Thiamine hydrochloride (4 mg/1) + Zinc oxide (20 mg/1) Tablet Oral Gm Pharmaceuticals 2013-11-11 Not applicable US Active OB Folic acid (1 mg/1) + Ascorbic acid (100 mg/1) + Cholecalciferol (400 [iU]/1) + Cupric sulfate pentahydrate (2 mg/1) + Cyanocobalamin (30 ug/1) + D-alpha-Tocopherol acetate (30 [iU]/1) + Doconexent (320 mg/1) + Iron (20 mg/1) + Pyridoxine hydrochloride (20 mg/1) + Riboflavin (4 mg/1) + Thiamine mononitrate (2 mg/1) + Zinc oxide (30 mg/1) Capsule, liquid filled Oral Gm Pharmaceuticals 2013-10-28 2017-03-31 US Animi-3 Folic acid (1 mg/1) + Cholecalciferol (1000 [iU]/1) + Cyanocobalamin (500 ug/1) + Doconexent (250 mg/1) + Icosapent (35 mg/1) + Omega-3 fatty acids (500 mg/1) + Pyridoxine hydrochloride (12.5 mg/1) + Soy sterol (200 mg/1) Capsule Oral Pbm Pharmaceuticals Inc. 2011-06-01 Not applicable US Animi-3 with Vitamin D Folic acid (1 mg/1) + Cholecalciferol (1000 [iU]/1) + Cyanocobalamin (500 ug/1) + Doconexent (250 mg/1) + Icosapent (35 mg/1) + Omega-3 fatty acids (500 mg/1) + Pyridoxine hydrochloride (12.5 mg/1) + Soy sterol (200 mg/1) Capsule Oral Pbm Pharmaceuticals Inc. 2011-06-01 Not applicable US
Categories
- ATC Codes
- B03AE02 — Iron, multivitamins and folic acid
- B03AE — Iron in other combinations
- B03A — IRON PREPARATIONS
- B03 — ANTIANEMIC PREPARATIONS
- B — BLOOD AND BLOOD FORMING ORGANS
- B03AD — Iron in combination with folic acid
- B03A — IRON PREPARATIONS
- B03 — ANTIANEMIC PREPARATIONS
- B — BLOOD AND BLOOD FORMING ORGANS
- B03AD — Iron in combination with folic acid
- B03A — IRON PREPARATIONS
- B03 — ANTIANEMIC PREPARATIONS
- B — BLOOD AND BLOOD FORMING ORGANS
- B03BB — Folic acid and derivatives
- B03B — VITAMIN B12 AND FOLIC ACID
- B03 — ANTIANEMIC PREPARATIONS
- B — BLOOD AND BLOOD FORMING ORGANS
- B03AD — Iron in combination with folic acid
- B03A — IRON PREPARATIONS
- B03 — ANTIANEMIC PREPARATIONS
- B — BLOOD AND BLOOD FORMING ORGANS
- B03BB — Folic acid and derivatives
- B03B — VITAMIN B12 AND FOLIC ACID
- B03 — ANTIANEMIC PREPARATIONS
- B — BLOOD AND BLOOD FORMING ORGANS
- B03AE — Iron in other combinations
- B03A — IRON PREPARATIONS
- B03 — ANTIANEMIC PREPARATIONS
- B — BLOOD AND BLOOD FORMING ORGANS
- B03AD — Iron in combination with folic acid
- B03A — IRON PREPARATIONS
- B03 — ANTIANEMIC PREPARATIONS
- B — BLOOD AND BLOOD FORMING ORGANS
- Drug Categories
- Antianemic Preparations
- Autacoids
- BCRP/ABCG2 Substrates
- Biological Factors
- Diagnostic Agents
- Diet, Food, and Nutrition
- Dietary Supplements
- Drugs that are Mainly Renally Excreted
- Folic Acid and Derivatives
- Food
- Growth Substances
- Hematinics
- Hematologic Agents
- Heterocyclic Compounds, Fused-Ring
- Micronutrients
- OAT1/SLC22A6 inhibitors
- Pteridines
- Pterins
- Supplements
- Vitamin B Complex
- Vitamin B12 and Folic Acid
- Vitamins
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as glutamic acid and derivatives. These are compounds containing glutamic acid or a derivative thereof resulting from reaction of glutamic acid at the amino group or the carboxy group, or from the replacement of any hydrogen of glycine by a heteroatom.
- Kingdom
- Organic compounds
- Super Class
- Organic acids and derivatives
- Class
- Carboxylic acids and derivatives
- Sub Class
- Amino acids, peptides, and analogues
- Direct Parent
- Glutamic acid and derivatives
- Alternative Parents
- N-acyl-alpha amino acids / Hippuric acids / Pterins and derivatives / Aminobenzamides / Phenylalkylamines / Aniline and substituted anilines / Benzoyl derivatives / Secondary alkylarylamines / Hydroxypyrimidines / Pyrazines show 10 more
- Substituents
- Amine / Amino acid / Aminobenzamide / Aminobenzoic acid or derivatives / Aniline or substituted anilines / Aralkylamine / Aromatic heteropolycyclic compound / Azacycle / Benzamide / Benzenoid show 30 more
- Molecular Framework
- Aromatic heteropolycyclic compounds
- External Descriptors
- N-acyl-amino acid, folic acids (CHEBI:27470) / Water-soluble vitamins (C00504)
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- 935E97BOY8
- CAS number
- 59-30-3
- InChI Key
- OVBPIULPVIDEAO-LBPRGKRZSA-N
- InChI
- InChI=1S/C19H19N7O6/c20-19-25-15-14(17(30)26-19)23-11(8-22-15)7-21-10-3-1-9(2-4-10)16(29)24-12(18(31)32)5-6-13(27)28/h1-4,8,12,21H,5-7H2,(H,24,29)(H,27,28)(H,31,32)(H3,20,22,25,26,30)/t12-/m0/s1
- IUPAC Name
- (2S)-2-[(4-{[(2-amino-4-oxo-1,4-dihydropteridin-6-yl)methyl]amino}phenyl)formamido]pentanedioic acid
- SMILES
- NC1=NC(=O)C2=NC(CNC3=CC=C(C=C3)C(=O)N[C@@H](CCC(O)=O)C(O)=O)=CN=C2N1
References
- Synthesis Reference
Carroll G. Temple, Jr., Robert D. Elliott, Jerry D. Rose, John A. Montgomery, "Preparation of tetrahydrofolic acid from folic acid." U.S. Patent US4206307, issued April, 1956.
US4206307- General References
- Kamen B: Folate and antifolate pharmacology. Semin Oncol. 1997 Oct;24(5 Suppl 18):S18-30-S18-39. [Article]
- Fenech M, Aitken C, Rinaldi J: Folate, vitamin B12, homocysteine status and DNA damage in young Australian adults. Carcinogenesis. 1998 Jul;19(7):1163-71. [Article]
- Zittoun J: [Anemias due to disorder of folate, vitamin B12 and transcobalamin metabolism]. Rev Prat. 1993 Jun 1;43(11):1358-63. [Article]
- Alaimo K, McDowell MA, Briefel RR, Bischof AM, Caughman CR, Loria CM, Johnson CL: Dietary intake of vitamins, minerals, and fiber of persons ages 2 months and over in the United States: Third National Health and Nutrition Examination Survey, Phase 1, 1988-91. Adv Data. 1994 Nov 14;(258):1-28. [Article]
- Raiten DJ, Fisher KD: Assessment of folate methodology used in the Third National Health and Nutrition Examination Survey (NHANES III, 1988-1994). J Nutr. 1995 May;125(5):1371S-1398S. [Article]
- Cylwik B, Chrostek L: [Disturbances of folic acid and homocysteine metabolism in alcohol abuse]. Pol Merkur Lekarski. 2011 Apr;30(178):295-9. [Article]
- Morrell MJ: Folic Acid and Epilepsy. Epilepsy Curr. 2002 Mar;2(2):31-34. doi: 10.1046/j.1535-7597.2002.00017.x. [Article]
- Scott JM, Weir DG, Molloy A, McPartlin J, Daly L, Kirke P: Folic acid metabolism and mechanisms of neural tube defects. Ciba Found Symp. 1994;181:180-7; discussion 187-91. [Article]
- Health Canada Prenatal Nutrition Guidelines for Health Professionals - Folate Contributes to a Healthy Pregnancy [Link]
- External Links
- Human Metabolome Database
- HMDB0000121
- KEGG Drug
- D00070
- KEGG Compound
- C00504
- PubChem Compound
- 6037
- PubChem Substance
- 46508092
- ChemSpider
- 5815
- BindingDB
- 50237629
- 4511
- ChEBI
- 27470
- ChEMBL
- CHEMBL1622
- ZINC
- ZINC000008577218
- Therapeutic Targets Database
- DAP001309
- PharmGKB
- PA449692
- PDBe Ligand
- FOL
- Drugs.com
- Drugs.com Drug Page
- PDRhealth
- PDRhealth Drug Page
- Wikipedia
- Folate
- PDB Entries
- 1cd2 / 1dhf / 1drf / 1dyi / 1pj6 / 1qzf / 1ra2 / 1ra8 / 1rb2 / 1rd7 … show 121 more
- FDA label
- Download (298 KB)
- MSDS
- Download (73.7 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 dataNot Available Active Not Recruiting Other Iron Deficiency Anemia (IDA) / Scoliosis Idiopathic / Ultra-short-term 1 somestatus stop reason just information to hide Not Available Completed Not Available Anemia 1 somestatus stop reason just information to hide Not Available Completed Not Available Anemia / Blood Loss Anemia / Erythropoiesis abnormal / Iron Deficiency (ID) / Iron Deficiency Anemia (IDA) / Iron Deficiency Anemia Treatment 1 somestatus stop reason just information to hide Not Available Completed Not Available Atherosclerosis / Human Immunodeficiency Virus (HIV) Infections / Inflammation 1 somestatus stop reason just information to hide Not Available Completed Not Available Inflammatory Bowel Diseases (IBD) / Psoriasis 1 somestatus stop reason just information to hide
Pharmacoeconomics
- Manufacturers
- App pharmaceuticals llc
- Ben venue laboratories inc
- Wyeth pharmaceuticals inc
- Barr laboratories inc
- Cadista pharmaceuticals inc
- Contract pharmacal corp
- Everylife
- Excellium pharmaceutical inc
- Halsey drug co inc
- Impax laboratories inc
- Invagen pharmaceuticals inc
- Ivax pharmaceuticals inc sub teva pharmaceuticals usa
- Lannett co inc
- Eli lilly and co
- Mk laboratories inc
- Mutual pharmaceutical co inc
- Nexgen pharma inc
- Pharmax group inc
- Pharmeral inc
- Pioneer pharmaceuticals inc
- Purepac pharmaceutical co
- Sandoz inc
- Tablicaps inc
- Udl laboratories inc
- Usl pharma inc
- Valeant pharmaceuticals international
- Vangard laboratories inc div midway medical co
- Vintage pharmaceuticals llc
- Vintage pharmaceuticals inc
- Watson laboratories
- Watson laboratories inc
- West ward pharmaceutical corp
- Whiteworth towne paulsen inc
- Mission pharmacal co
- Packagers
- Accucaps Industries Ltd.
- Advanced Pharmaceutical Services Inc.
- Ajanta Pharma Ltd.
- Amend
- Amerisource Health Services Corp.
- Apace Packaging
- Apotheca Inc.
- APP Pharmaceuticals
- A-S Medication Solutions LLC
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- Dosage Forms
Form Route Strength Tablet, coated Oral 1 mg Tablet Oral 1 mg Solution Oral 10 mg Tablet, film coated Oral 10 mg Tablet, coated Oral 5 mg Tablet Oral 400 MCG Solution Intramuscular; Intravenous; Subcutaneous 1 mg Solution Intramuscular; Intravenous; Subcutaneous 100000 mg Tablet Oral 0.005 g Tablet Oral 5 g Capsule, coated Oral 1 mg Solution Intravenous 1.914 mg Bar, chewable Oral Solution Oral Patch Transdermal Tablet Oral 400 MICROGRAMMI Granule, effervescent Oral Injection, powder, for solution Intramuscular; Intravenous Injection, powder, for solution Parenteral Injection, powder, for solution Intravenous Kit; tablet; tablet, film coated Oral Tablet Capsule Capsule Cutaneous; Oral Tablet Oral 5 mg/1 Capsule, delayed release pellets Oral Injection, solution Intramuscular; Intravenous Injection, powder, for solution Intramuscular Tablet Oral 350 mcg Tablet Oral 5.00 mg Tablet, film coated Oral 101 mg Tablet, extended release Oral Suspension Oral Capsule Oral 162 mg Lozenge Oral Syrup Oral Capsule, liquid filled; kit; tablet Oral Injection, solution Intramuscular; Intravenous; Subcutaneous 5 mg/1mL Tablet Oral 1 mg/1 Tablet Oral 400 ug/1 Tablet Oral 800 ug/1 Tablet Oral 0.4 mg / tab Tablet Oral 1 mg / tab Tablet Oral 1.0 mg Tablet Oral 400 cg Tablet Oral .4 mg / tab Tablet Oral .8 mg Capsule Oral 1 mg / cap Tablet, extended release Oral 800 mcg / tab Liquid Intramuscular; Intravenous; Subcutaneous 5 mg / mL Solution Intramuscular; Intravenous; Subcutaneous 5 mg / mL Tablet Oral 25 mg Tablet Oral 5 mg / tab Tablet Oral 0.8 mg / tab Capsule Oral 1.66 mg/1 Capsule Oral 5 MG Injection, solution 15 MG/2ML Injection, solution Intramuscular 15 mg/2mL Tablet Oral 4 mg Gel Oral Capsule, delayed release Oral Tablet Oral 800 cg Tablet Oral 800 mcg Tablet Oral 5.000 mg Tablet, coated Oral 150 mcg Tablet, coated Oral Tablet, sugar coated Oral Tablet, effervescent Oral Solution / drops Oral Liquid Oral Capsule, coated Oral 400 cg Injection, solution, concentrate; kit Intravenous Injection, powder, lyophilized, for solution Intravenous Kit Intravenous Tablet, chewable Oral Solution Intravenous Tablet Oral Liquid Intravenous Solution Parenteral Tablet, orally disintegrating Oral Capsule, gelatin coated; kit; tablet Oral Tablet Oral Powder, for solution Oral Gum, chewing Oral Powder Injection, solution; kit Intravenous Injection, solution Intravenous Capsule, liquid filled; kit; tablet, coated Oral Tablet, film coated Oral Capsule, gelatin coated Oral Pill Oral Wafer Oral Capsule; kit; tablet, coated Oral Powder, for solution Intravenous Injection, powder, for solution Intravenous 100 mg Capsule, extended release Oral Tablet, film coated Oral 180 mg Tablet, sugar coated Oral 60 mg Tablet, film coated Oral 60 mg Kit; tablet; tablet, coated Oral Capsule Oral Capsule; kit; tablet, film coated Oral Capsule, coated Oral Capsule; kit; tablet Oral Injection, powder, lyophilized, for solution Intramuscular; Intravenous Strip Oral Tablet, film coated Oral 5 MG Capsule, liquid filled; kit Oral Capsule, liquid filled Oral Kit Oral Powder Oral Tablet Oral 0.8 mg Tablet, sugar coated Oral Tablet Oral 0.5 mg Solution Tablet Oral 0.4 mg Tablet Oral 5 mg Tablet, film coated - Prices
Unit description Cost Unit Folic acid 5 mg/ml vial 2.14USD ml Folic Acid 5 mg/ml 2.04USD ml Folic acid powder 1.68USD g Folvite 5 mg/ml vial 1.38USD ml Folic Acid 1 mg tablet 0.15USD tablet Folic acid 400 mcg tablet 0.07USD tablet Apo-Folic 5 mg Tablet 0.04USD tablet CVS Pharmacy folic acid 800 mcg tablet 0.02USD tablet Folic acid 0.4 mg tablet 0.02USD tablet Folic acid 0.8 mg tablet 0.02USD tablet DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
Property Value Source logP -2.5 Not Available - Predicted Properties
Property Value Source Water Solubility 0.0761 mg/mL ALOGPS logP -0.04 ALOGPS logP -0.69 Chemaxon logS -3.8 ALOGPS pKa (Strongest Acidic) 3.38 Chemaxon pKa (Strongest Basic) 2.12 Chemaxon Physiological Charge -2 Chemaxon Hydrogen Acceptor Count 12 Chemaxon Hydrogen Donor Count 6 Chemaxon Polar Surface Area 208.99 Å2 Chemaxon Rotatable Bond Count 9 Chemaxon Refractivity 111.01 m3·mol-1 Chemaxon Polarizability 42.06 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
Property Value Probability Human Intestinal Absorption + 0.7956 Blood Brain Barrier + 0.7609 Caco-2 permeable - 0.844 P-glycoprotein substrate Substrate 0.687 P-glycoprotein inhibitor I Non-inhibitor 0.9795 P-glycoprotein inhibitor II Non-inhibitor 0.9969 Renal organic cation transporter Non-inhibitor 0.876 CYP450 2C9 substrate Non-substrate 0.8276 CYP450 2D6 substrate Non-substrate 0.7947 CYP450 3A4 substrate Non-substrate 0.6212 CYP450 1A2 substrate Non-inhibitor 0.9281 CYP450 2C9 inhibitor Non-inhibitor 0.9071 CYP450 2D6 inhibitor Non-inhibitor 0.9435 CYP450 2C19 inhibitor Non-inhibitor 0.916 CYP450 3A4 inhibitor Non-inhibitor 0.9075 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.974 Ames test Non AMES toxic 0.8724 Carcinogenicity Non-carcinogens 0.9521 Biodegradation Not ready biodegradable 0.9191 Rat acute toxicity 2.4490 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.9529 hERG inhibition (predictor II) Non-inhibitor 0.8444
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 237.1422366 predictedDarkChem Lite v0.1.0 [M-H]- 226.6961011 predictedDarkChem Standard v0.1.0 [M-H]- 236.9919366 predictedDarkChem Lite v0.1.0 [M-H]- 237.1352366 predictedDarkChem Lite v0.1.0 [M-H]- 236.3994366 predictedDarkChem Lite v0.1.0 [M-H]- 192.52687 predictedDeepCCS 1.0 (2019) [M+H]+ 235.5291366 predictedDarkChem Lite v0.1.0 [M+H]+ 235.2513366 predictedDarkChem Lite v0.1.0 [M+H]+ 235.3218366 predictedDarkChem Lite v0.1.0 [M+H]+ 235.9142366 predictedDarkChem Lite v0.1.0 [M+H]+ 235.5316366 predictedDarkChem Lite v0.1.0 [M+H]+ 194.92244 predictedDeepCCS 1.0 (2019) [M+Na]+ 236.9034366 predictedDarkChem Lite v0.1.0 [M+Na]+ 205.6878953 predictedDarkChem Standard v0.1.0 [M+Na]+ 236.2095366 predictedDarkChem Lite v0.1.0 [M+Na]+ 237.0942366 predictedDarkChem Lite v0.1.0 [M+Na]+ 236.6215366 predictedDarkChem Lite v0.1.0 [M+Na]+ 200.94067 predictedDeepCCS 1.0 (2019)
Targets
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Modulator
- 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
- Zhou Y, Zhang Y, Zhao D, Yu X, Shen X, Zhou Y, Wang S, Qiu Y, Chen Y, Zhu F: TTD: Therapeutic Target Database describing target druggability information. Nucleic Acids Res. 2024 Jan 5;52(D1):D1465-D1477. doi: 10.1093/nar/gkad751. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Modulator
- 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
- Zhou Y, Zhang Y, Zhao D, Yu X, Shen X, Zhou Y, Wang S, Qiu Y, Chen Y, Zhu F: TTD: Therapeutic Target Database describing target druggability information. Nucleic Acids Res. 2024 Jan 5;52(D1):D1465-D1477. doi: 10.1093/nar/gkad751. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Binder
- General Function
- Binds to folate and reduced folic acid derivatives and mediates delivery of 5-methyltetrahydrofolate to the interior of cells. Isoform Short does not bind folate.
- Specific Function
- folic acid binding
- Gene Name
- FOLR3
- Uniprot ID
- P41439
- Uniprot Name
- Folate receptor gamma
- Molecular Weight
- 27884.28 Da
References
- Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [Article]
- Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [Article]
- Shen F, Ross JF, Wang X, Ratnam M: Identification of a novel folate receptor, a truncated receptor, and receptor type beta in hematopoietic cells: cDNA cloning, expression, immunoreactivity, and tissue specificity. Biochemistry. 1994 Feb 8;33(5):1209-15. [Article]
- Shen F, Wu M, Ross JF, Miller D, Ratnam M: Folate receptor type gamma is primarily a secretory protein due to lack of an efficient signal for glycosylphosphatidylinositol modification: protein characterization and cell type specificity. Biochemistry. 1995 Apr 25;34(16):5660-5. [Article]
- Prasad PD, Ramamoorthy S, Moe AJ, Smith CH, Leibach FH, Ganapathy V: Selective expression of the high-affinity isoform of the folate receptor (FR-alpha) in the human placental syncytiotrophoblast and choriocarcinoma cells. Biochim Biophys Acta. 1994 Aug 11;1223(1):71-5. [Article]
- Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Binder
- General Function
- Binds to folate and reduced folic acid derivatives and mediates delivery of 5-methyltetrahydrofolate and folate analogs into the interior of cells. Has high affinity for folate and folic acid analogs at neutral pH. Exposure to slightly acidic pH after receptor endocytosis triggers a conformation change that strongly reduces its affinity for folates and mediates their release.
- Specific Function
- folic acid binding
- Gene Name
- FOLR2
- Uniprot ID
- P14207
- Uniprot Name
- Folate receptor beta
- Molecular Weight
- 29279.31 Da
References
- Dixit V, Van den Bossche J, Sherman DM, Thompson DH, Andres RP: Synthesis and grafting of thioctic acid-PEG-folate conjugates onto Au nanoparticles for selective targeting of folate receptor-positive tumor cells. Bioconjug Chem. 2006 May-Jun;17(3):603-9. [Article]
- Wlodarczyk BJ, Cabrera RM, Hill DS, Bozinov D, Zhu H, Finnell RH: Arsenic-induced gene expression changes in the neural tube of folate transport defective mouse embryos. Neurotoxicology. 2006 Jul;27(4):547-57. Epub 2006 Apr 18. [Article]
- Boyles AL, Billups AV, Deak KL, Siegel DG, Mehltretter L, Slifer SH, Bassuk AG, Kessler JA, Reed MC, Nijhout HF, George TM, Enterline DS, Gilbert JR, Speer MC: Neural tube defects and folate pathway genes: family-based association tests of gene-gene and gene-environment interactions. Environ Health Perspect. 2006 Oct;114(10):1547-52. [Article]
- Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General Function
- Binds to folate and reduced folic acid derivatives and mediates delivery of 5-methyltetrahydrofolate and folate analogs into the interior of cells (PubMed:19074442, PubMed:23851396, PubMed:23934049, PubMed:2527252, PubMed:8033114, PubMed:8567728). Has high affinity for folate and folic acid analogs at neutral pH (PubMed:23851396, PubMed:23934049, PubMed:2527252, PubMed:8033114, PubMed:8567728). Exposure to slightly acidic pH after receptor endocytosis triggers a conformation change that strongly reduces its affinity for folates and mediates their release (PubMed:8567728). Required for normal embryonic development and normal cell proliferation (By similarity).
- Specific Function
- folic acid binding
- Gene Name
- FOLR1
- Uniprot ID
- P15328
- Uniprot Name
- Folate receptor alpha
- Molecular Weight
- 29818.94 Da
References
- Wang L, Desmoulin SK, Cherian C, Polin L, White K, Kushner J, Fulterer A, Chang MH, Mitchell-Ryan S, Stout M, Romero MF, Hou Z, Matherly LH, Gangjee A: Synthesis, biological, and antitumor activity of a highly potent 6-substituted pyrrolo[2,3-d]pyrimidine thienoyl antifolate inhibitor with proton-coupled folate transporter and folate receptor selectivity over the reduced folate carrier that inhibits beta-glycinamide ribonucleotide formyltransferase. J Med Chem. 2011 Oct 27;54(20):7150-64. doi: 10.1021/jm200739e. Epub 2011 Sep 22. [Article]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Hydrolyzes the polyglutamate sidechains of pteroylpolyglutamates. Progressively removes gamma-glutamyl residues from pteroylpoly-gamma-glutamate to yield pteroyl-alpha-glutamate (folic acid) and free glutamate (PubMed:11005824, PubMed:8816764). May play an important role in the bioavailability of dietary pteroylpolyglutamates and in the metabolism of pteroylpolyglutamates and antifolates.
- Specific Function
- exopeptidase activity
- Gene Name
- GGH
- Uniprot ID
- Q92820
- Uniprot Name
- Gamma-glutamyl hydrolase
- Molecular Weight
- 35964.045 Da
References
- Schneider E, Ryan TJ: Gamma-glutamyl hydrolase and drug resistance. Clin Chim Acta. 2006 Dec;374(1-2):25-32. Epub 2006 Jun 10. [Article]
- Eisele LE, Chave KJ, Lehning AC, Ryan TJ: Characterization of Human gamma-glutamyl hydrolase in solution demonstrates that the enzyme is a non-dissociating homodimer. Biochim Biophys Acta. 2006 Sep;1764(9):1479-86. Epub 2006 Jul 12. [Article]
- Chen L, Eitenmiller RR: Optimization of the trienzyme extraction for the microbiological assay of folate in vegetables. J Agric Food Chem. 2007 May 16;55(10):3884-8. Epub 2007 Apr 17. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Catalyzes the conversion of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate, a cosubstrate for homocysteine remethylation to methionine (PubMed:29891918). Represents a key regulatory connection between the folate and methionine cycles (Probable).
- Specific Function
- FAD binding
- Gene Name
- MTHFR
- Uniprot ID
- P42898
- Uniprot Name
- Methylenetetrahydrofolate reductase (NADPH)
- Molecular Weight
- 74595.895 Da
References
- West AA, Caudill MA: Genetic variation: impact on folate (and choline) bioefficacy. Int J Vitam Nutr Res. 2010 Oct;80(4-5):319-29. doi: 10.1024/0300-9831/a000040. [Article]
- Kim YI: Role of the MTHFR polymorphisms in cancer risk modification and treatment. Future Oncol. 2009 May;5(4):523-42. doi: 10.2217/fon.09.26. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Substrate
- General Function
- Key enzyme in folate metabolism. Contributes to the de novo mitochondrial thymidylate biosynthesis pathway. Catalyzes an essential reaction for de novo glycine and purine synthesis, and for DNA precursor synthesis. Binds its own mRNA and that of DHFR2.
- Specific Function
- dihydrofolate reductase activity
- Gene Name
- DHFR
- Uniprot ID
- P00374
- Uniprot Name
- Dihydrofolate reductase
- Molecular Weight
- 21452.61 Da
Transporters
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- ATP-dependent transporter of the ATP-binding cassette (ABC) family that actively extrudes physiological compounds and xenobiotics from cells. Plays a role in physiological processes involving bile acids, conjugated steroids and cyclic nucleotides, including cAMP and cGMP (PubMed:12764137, PubMed:15537867). Mediates the ATP-dependent efflux of a range of physiological lipophilic anions, including the glutathione S-conjugates leukotriene C4 and dinitrophenyl S-glutathione, steroid sulfates, such as dehydroepiandrosterone 3-sulfate (DHEAS) and estrone 3-sulfate, glucuronides such as estradiol 17-beta-D-glucuronide (E(2)17betaG), the monoanionic bile acids glycocholate and taurocholate, and methotrexate (PubMed:15537867, PubMed:16359813, PubMed:25896536). Plays a role in the transport of earwax components (PubMed:16444273, PubMed:19383836). Participates in the secretion of odorants and their precursors from the apocrine sweat glands, including the secretion of glutamine conjugates, as well as the Cys-Gly-(S) conjugates of 3-methyl-3-sulfanyl-hexanol (PubMed:19710689). Involved in the cellular extrusion of nucleotide analogs, hence confering resistance to various drugs, including clinically relevant drugs such as 5-fluorouracil (5-FU) and methotrexate (PubMed:12764137, PubMed:15537867, PubMed:25896536).
- Specific Function
- ABC-type bile acid transporter activity
- Gene Name
- ABCC11
- Uniprot ID
- Q96J66
- Uniprot Name
- ATP-binding cassette sub-family C member 11
- Molecular Weight
- 154299.625 Da
References
- Chen ZS, Guo Y, Belinsky MG, Kotova E, Kruh GD: Transport of bile acids, sulfated steroids, estradiol 17-beta-D-glucuronide, and leukotriene C4 by human multidrug resistance protein 8 (ABCC11). Mol Pharmacol. 2005 Feb;67(2):545-57. Epub 2004 Nov 10. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- ATP-dependent transporter of the ATP-binding cassette (ABC) family that binds and hydrolyzes ATP to enable active transport of various substrates including many drugs, toxicants and endogenous compound across cell membranes (PubMed:10359813, PubMed:11581266, PubMed:15083066). Transports glucuronide conjugates such as bilirubin diglucuronide, estradiol-17-beta-o-glucuronide and GSH conjugates such as leukotriene C4 (LTC4) (PubMed:11581266, PubMed:15083066). Transports also various bile salts (taurocholate, glycocholate, taurochenodeoxycholate-3-sulfate, taurolithocholate- 3-sulfate) (By similarity). Does not contribute substantially to bile salt physiology but provides an alternative route for the export of bile acids and glucuronides from cholestatic hepatocytes (By similarity). May contribute to regulate the transport of organic compounds in testes across the blood-testis-barrier (Probable). Can confer resistance to various anticancer drugs, methotrexate, tenoposide and etoposide, by decreasing accumulation of these drugs in cells (PubMed:10359813, PubMed:11581266).
- Specific Function
- ABC-type bile acid transporter activity
- Gene Name
- ABCC3
- Uniprot ID
- O15438
- Uniprot Name
- ATP-binding cassette sub-family C member 3
- Molecular Weight
- 169341.14 Da
References
- Zeng H, Chen ZS, Belinsky MG, Rea PA, Kruh GD: Transport of methotrexate (MTX) and folates by multidrug resistance protein (MRP) 3 and MRP1: effect of polyglutamylation on MTX transport. Cancer Res. 2001 Oct 1;61(19):7225-32. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Secondary active transporter that functions as a Na(+)-independent organic anion (OA)/dicarboxylate antiporter where the uptake of one molecule of OA into the cell is coupled with an efflux of one molecule of intracellular dicarboxylate such as 2-oxoglutarate or glutarate (PubMed:11669456, PubMed:11907186, PubMed:14675047, PubMed:22108572, PubMed:23832370, PubMed:28534121, PubMed:9950961). Mediates the uptake of OA across the basolateral side of proximal tubule epithelial cells, thereby contributing to the renal elimination of endogenous OA from the systemic circulation into the urine (PubMed:9887087). Functions as a biopterin transporters involved in the uptake and the secretion of coenzymes tetrahydrobiopterin (BH4), dihydrobiopterin (BH2) and sepiapterin to urine, thereby determining baseline levels of blood biopterins (PubMed:28534121). Transports prostaglandin E2 (PGE2) and prostaglandin F2-alpha (PGF2-alpha) and may contribute to their renal excretion (PubMed:11907186). Also mediates the uptake of cyclic nucleotides such as cAMP and cGMP (PubMed:26377792). Involved in the transport of neuroactive tryptophan metabolites kynurenate (KYNA) and xanthurenate (XA) and may contribute to their secretion from the brain (PubMed:22108572, PubMed:23832370). May transport glutamate (PubMed:26377792). Also involved in the disposition of uremic toxins and potentially toxic xenobiotics by the renal organic anion secretory pathway, helping reduce their undesired toxicological effects on the body (PubMed:11669456, PubMed:14675047). Uremic toxins include the indoxyl sulfate (IS), hippurate/N-benzoylglycine (HA), indole acetate (IA), 3-carboxy-4- methyl-5-propyl-2-furanpropionate (CMPF) and urate (PubMed:14675047, PubMed:26377792). Xenobiotics include the mycotoxin ochratoxin (OTA) (PubMed:11669456). May also contribute to the transport of organic compounds in testes across the blood-testis-barrier (PubMed:35307651).
- Specific Function
- alpha-ketoglutarate transmembrane transporter activity
- Gene Name
- SLC22A6
- Uniprot ID
- Q4U2R8
- Uniprot Name
- Solute carrier family 22 member 6
- Molecular Weight
- 61815.78 Da
References
- Kuze K, Graves P, Leahy A, Wilson P, Stuhlmann H, You G: Heterologous expression and functional characterization of a mouse renal organic anion transporter in mammalian cells. J Biol Chem. 1999 Jan 15;274(3):1519-24. [Article]
- Uwai Y, Okuda M, Takami K, Hashimoto Y, Inui K: Functional characterization of the rat multispecific organic anion transporter OAT1 mediating basolateral uptake of anionic drugs in the kidney. FEBS Lett. 1998 Nov 6;438(3):321-4. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- ATP-dependent transporter of the ATP-binding cassette (ABC) family that actively extrudes physiological compounds and xenobiotics from cells. Transports a range of endogenous molecules that have a key role in cellular communication and signaling, including cyclic nucleotides such as cyclic AMP (cAMP) and cyclic GMP (cGMP), bile acids, steroid conjugates, urate, and prostaglandins (PubMed:11856762, PubMed:12523936, PubMed:12835412, PubMed:12883481, PubMed:15364914, PubMed:15454390, PubMed:16282361, PubMed:17959747, PubMed:18300232, PubMed:26721430). Mediates the ATP-dependent efflux of glutathione conjugates such as leukotriene C4 (LTC4) and leukotriene B4 (LTB4) too. The presence of GSH is necessary for the ATP-dependent transport of LTB4, whereas GSH is not required for the transport of LTC4 (PubMed:17959747). Mediates the cotransport of bile acids with reduced glutathione (GSH) (PubMed:12523936, PubMed:12883481, PubMed:16282361). Transports a wide range of drugs and their metabolites, including anticancer, antiviral and antibiotics molecules (PubMed:11856762, PubMed:12105214, PubMed:15454390, PubMed:17344354, PubMed:18300232). Confers resistance to anticancer agents such as methotrexate (PubMed:11106685).
- Specific Function
- 15-hydroxyprostaglandin dehydrogenase (NAD+) activity
- Gene Name
- ABCC4
- Uniprot ID
- O15439
- Uniprot Name
- ATP-binding cassette sub-family C member 4
- Molecular Weight
- 149525.33 Da
References
- Chen ZS, Lee K, Walther S, Raftogianis RB, Kuwano M, Zeng H, Kruh GD: Analysis of methotrexate and folate transport by multidrug resistance protein 4 (ABCC4): MRP4 is a component of the methotrexate efflux system. Cancer Res. 2002 Jun 1;62(11):3144-50. [Article]
- Rius M, Nies AT, Hummel-Eisenbeiss J, Jedlitschky G, Keppler D: Cotransport of reduced glutathione with bile salts by MRP4 (ABCC4) localized to the basolateral hepatocyte membrane. Hepatology. 2003 Aug;38(2):374-84. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Broad substrate specificity ATP-dependent transporter of the ATP-binding cassette (ABC) family that actively extrudes a wide variety of physiological compounds, dietary toxins and xenobiotics from cells (PubMed:11306452, PubMed:12958161, PubMed:19506252, PubMed:20705604, PubMed:28554189, PubMed:30405239, PubMed:31003562). Involved in porphyrin homeostasis, mediating the export of protoporphyrin IX (PPIX) from both mitochondria to cytosol and cytosol to extracellular space, it also functions in the cellular export of heme (PubMed:20705604, PubMed:23189181). Also mediates the efflux of sphingosine-1-P from cells (PubMed:20110355). Acts as a urate exporter functioning in both renal and extrarenal urate excretion (PubMed:19506252, PubMed:20368174, PubMed:22132962, PubMed:31003562, PubMed:36749388). In kidney, it also functions as a physiological exporter of the uremic toxin indoxyl sulfate (By similarity). Also involved in the excretion of steroids like estrone 3-sulfate/E1S, 3beta-sulfooxy-androst-5-en-17-one/DHEAS, and other sulfate conjugates (PubMed:12682043, PubMed:28554189, PubMed:30405239). Mediates the secretion of the riboflavin and biotin vitamins into milk (By similarity). Extrudes pheophorbide a, a phototoxic porphyrin catabolite of chlorophyll, reducing its bioavailability (By similarity). Plays an important role in the exclusion of xenobiotics from the brain (Probable). It confers to cells a resistance to multiple drugs and other xenobiotics including mitoxantrone, pheophorbide, camptothecin, methotrexate, azidothymidine, and the anthracyclines daunorubicin and doxorubicin, through the control of their efflux (PubMed:11306452, PubMed:12477054, PubMed:15670731, PubMed:18056989, PubMed:31254042). In placenta, it limits the penetration of drugs from the maternal plasma into the fetus (By similarity). May play a role in early stem cell self-renewal by blocking differentiation (By similarity).
- Specific Function
- ABC-type xenobiotic transporter activity
- Gene Name
- ABCG2
- Uniprot ID
- Q9UNQ0
- Uniprot Name
- Broad substrate specificity ATP-binding cassette transporter ABCG2
- Molecular Weight
- 72313.47 Da
References
- Chen ZS, Robey RW, Belinsky MG, Shchaveleva I, Ren XQ, Sugimoto Y, Ross DD, Bates SE, Kruh GD: Transport of methotrexate, methotrexate polyglutamates, and 17beta-estradiol 17-(beta-D-glucuronide) by ABCG2: effects of acquired mutations at R482 on methotrexate transport. Cancer Res. 2003 Jul 15;63(14):4048-54. [Article]
- 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
- Nakai Y, Inoue K, Abe N, Hatakeyama M, Ohta KY, Otagiri M, Hayashi Y, Yuasa H: Functional characterization of human proton-coupled folate transporter/heme carrier protein 1 heterologously expressed in mammalian cells as a folate transporter. J Pharmacol Exp Ther. 2007 Aug;322(2):469-76. Epub 2007 May 2. [Article]
- Ashokkumar B, Mohammed ZM, Vaziri ND, Said HM: Effect of folate oversupplementation on folate uptake by human intestinal and renal epithelial cells. Am J Clin Nutr. 2007 Jul;86(1):159-66. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Facilitates flavin adenine dinucleotide (FAD) translocation across the mitochondrial inner membrane into the mitochondrial matrix where it acts as a redox cofactor to assist flavoenzyme activities in fundamental metabolic processes including fatty acid beta-oxidation, amino acid and choline metabolism as well as mitochondrial electron transportation. In particular, provides FAD to DLD dehydrogenase of the glycine cleavage system, part of mitochondrial one-carbon metabolic pathway involved in neural tube closure in early embryogenesis.
- Specific Function
- FAD transmembrane transporter activity
- Gene Name
- SLC25A32
- Uniprot ID
- Q9H2D1
- Uniprot Name
- Solute carrier family 25 member 32
- Molecular Weight
- 35406.83 Da
References
- Salbaum JM, Kappen C: Genetic and epigenomic footprints of folate. Prog Mol Biol Transl Sci. 2012;108:129-58. doi: 10.1016/B978-0-12-398397-8.00006-X. [Article]
Drug created at June 13, 2005 13:24 / Updated at September 27, 2024 07:15