FOLIC ACID
General Information
| Mainterm | FOLIC ACID |
| Doc Type | ASP |
| CAS Reg.No.(or other ID) | 59-30-3 |
| Regnum |
139.122 101.79 101.9 107.100 137.165 137.185 137.235 137.260 137.305 137.350 139.115 139.155 172.345 172.896 |
From www.fda.gov
Computed Descriptors
Download SDF| 2D Structure | |
| CID | 6037 |
| IUPAC Name | (2S)-2-[[4-[(2-amino-4-oxo-1H-pteridin-6-yl)methylamino]benzoyl]amino]pentanedioic acid |
| 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 |
| InChI Key | OVBPIULPVIDEAO-LBPRGKRZSA-N |
| Canonical SMILES | C1=CC(=CC=C1C(=O)NC(CCC(=O)O)C(=O)O)NCC2=CN=C3C(=N2)C(=O)N=C(N3)N |
| Molecular Formula | C19H19N7O6 |
| Wikipedia | folic acid dihydrate |
From Pubchem
Computed Properties
| Property Name | Property Value |
|---|---|
| Molecular Weight | 441.404 |
| Hydrogen Bond Donor Count | 6 |
| Hydrogen Bond Acceptor Count | 9 |
| Rotatable Bond Count | 9 |
| Complexity | 767.0 |
| CACTVS Substructure Key Fingerprint | A A A D c e B 7 u A A A A A A A A A A A A A A A A A A A A A A A A A A 8 Q I A A A A A A A A C B w A A A H g A Q C A A A D C j B n g Q 9 + J L I E g C o A z f 3 f A C C g C 0 3 E i A J 2 I G 4 d M i K Y H r A 3 b G U Y Y h s l g L Y y e e 8 r w C e C A A A A A A A A A A Q A A A A A A A A A A A A A A A A A A = = |
| Topological Polar Surface Area | 209.0 |
| Monoisotopic Mass | 441.14 |
| Exact Mass | 441.14 |
| XLogP3 | None |
| XLogP3-AA | -1.1 |
| Compound Is Canonicalized | True |
| Formal Charge | 0 |
| Heavy Atom Count | 32 |
| Defined Atom Stereocenter Count | 1 |
| Undefined Atom Stereocenter Count | 0 |
| Defined Bond Stereocenter Count | 0 |
| Undefined Bond Stereocenter Count | 0 |
| Isotope Atom Count | 0 |
| Covalently-Bonded Unit Count | 1 |
From Pubchem
Food Additives Biosynthesis/Degradation
ADMET Predicted Profile --- Classification
| Model | Result | Probability |
|---|---|---|
| Absorption | ||
| Blood-Brain Barrier | BBB+ | 0.7609 |
| Human Intestinal Absorption | HIA+ | 0.7956 |
| Caco-2 Permeability | Caco2- | 0.8440 |
| P-glycoprotein Substrate | Substrate | 0.6870 |
| P-glycoprotein Inhibitor | Non-inhibitor | 0.9795 |
| Non-inhibitor | 0.9969 | |
| Renal Organic Cation Transporter | Non-inhibitor | 0.8760 |
| Distribution | ||
| Subcellular localization | Mitochondria | 0.4625 |
| Metabolism | ||
| CYP450 2C9 Substrate | Non-substrate | 0.8276 |
| CYP450 2D6 Substrate | Non-substrate | 0.7947 |
| CYP450 3A4 Substrate | Non-substrate | 0.6212 |
| CYP450 1A2 Inhibitor | Non-inhibitor | 0.9281 |
| CYP450 2C9 Inhibitor | Non-inhibitor | 0.9071 |
| CYP450 2D6 Inhibitor | Non-inhibitor | 0.9435 |
| CYP450 2C19 Inhibitor | Non-inhibitor | 0.9160 |
| CYP450 3A4 Inhibitor | Non-inhibitor | 0.9075 |
| CYP Inhibitory Promiscuity | Low CYP Inhibitory Promiscuity | 0.9740 |
| Excretion | ||
| Toxicity | ||
| Human Ether-a-go-go-Related Gene Inhibition | Weak inhibitor | 0.9529 |
| Non-inhibitor | 0.8444 | |
| AMES Toxicity | Non AMES toxic | 0.8724 |
| Carcinogens | Non-carcinogens | 0.9521 |
| Fish Toxicity | Low FHMT | 0.5594 |
| Tetrahymena Pyriformis Toxicity | High TPT | 0.5269 |
| Honey Bee Toxicity | Low HBT | 0.8225 |
| Biodegradation | Not ready biodegradable | 0.9191 |
| Acute Oral Toxicity | III | 0.6157 |
| Carcinogenicity (Three-class) | Non-required | 0.6643 |
From admetSAR
ADMET Predicted Profile --- Regression
| Model | Value | Unit |
|---|---|---|
| Absorption | ||
| Aqueous solubility | -3.3434 | LogS |
| Caco-2 Permeability | -1.0743 | LogPapp, cm/s |
| Distribution | ||
| Metabolism | ||
| Excretion | ||
| Toxicity | ||
| Rat Acute Toxicity | 2.4490 | LD50, mol/kg |
| Fish Toxicity | 1.7717 | pLC50, mg/L |
| Tetrahymena Pyriformis Toxicity | 0.1453 | pIGC50, ug/L |
From admetSAR
Toxicity Profile
| Route of Exposure | Intravenous, Oral |
|---|---|
| Mechanism of Toxicity | Folic acid, as it is biochemically inactive, is converted to tetrahydrofolic acid and methyltetrahydrofolate by dihydrofolate reductase. 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. |
| Metabolism | Hepatic Route of Elimination: Folic Acid is metabolized in the liver to 7, 8-dihydrofolic acid and eventually to 5,6,7,8-tetrahydrofolic acid with the aid of reduced diphosphopyridine nucleotide (DPNH) and folate reductases. A majority of the metabolic products appeared in the urine after 6 hours; excretion was generally complete within 24 hours. Folic Acid is also excreted in the milk of lactating mothers. |
| Toxicity Values | LD50: 85 mg/kg (Intraperitoneal, Mouse) LD50: 120 mg/kg (Intravenous, Guinea pig) LD50: 239 mg/kg (Intravenous Mouse) LD50: 500 mg/kg (Intravenous, Rat) LD50: 410 mg/kg (Intravenous, Rabbit) |
| Lethal Dose | None |
| Carcinogenicity (IARC Classification) | No indication of carcinogenicity to humans (not listed by IARC). |
| Minimum Risk Level | None |
| Health Effects | None |
| Treatment | None |
| Reference |
|
From T3DB
Taxonomic Classification
| Kingdom | Organic compounds |
|---|---|
| Superclass | Organic acids and derivatives |
| Class | Carboxylic acids and derivatives |
| Subclass | Amino acids, peptides, and analogues |
| Intermediate Tree Nodes | Amino acids and derivatives - Alpha amino acids and derivatives |
| Direct Parent | Glutamic acid and derivatives |
| Alternative Parents |
|
| Molecular Framework | Aromatic heteropolycyclic compounds |
| Substituents | Glutamic acid or derivatives - N-acyl-alpha-amino acid - N-acyl-alpha amino acid or derivatives - Hippuric acid - Hippuric acid or derivatives - Pterin - Aminobenzamide - Aminobenzoic acid or derivatives - Pteridine - Benzamide - Benzoic acid or derivatives - Benzoyl - Phenylalkylamine - Aniline or substituted anilines - Hydroxypyrimidine - Aralkylamine - Secondary aliphatic/aromatic amine - Monocyclic benzene moiety - Pyrimidine - Pyrazine - Dicarboxylic acid or derivatives - Benzenoid - Heteroaromatic compound - Carboxamide group - Amino acid - Secondary carboxylic acid amide - Azacycle - Organoheterocyclic compound - Carboxylic acid - Secondary amine - Organic nitrogen compound - Carbonyl group - Amine - Hydrocarbon derivative - Organic oxide - Organopnictogen compound - Organic oxygen compound - Organooxygen compound - Organonitrogen compound - Aromatic heteropolycyclic compound |
| 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. |
From ClassyFire
Targets
- General Function:
- Folic acid binding
- Specific 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.
- Gene Name:
- FOLR3
- Uniprot ID:
- P41439
- Molecular Weight:
- 27638.0 Da
References
- 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. [8061055 ]
- General Function:
- Methotrexate binding
- Specific 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.
- Gene Name:
- FOLR2
- Uniprot ID:
- P14207
- Molecular Weight:
- 29279.31 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. [21879757 ]
- General Function:
- Omega peptidase activity
- Specific 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. May play an important role in the bioavailability of dietary pteroylpolyglutamates and in the metabolism of pteroylpolyglutamates and antifolates.
- Gene Name:
- GGH
- Uniprot ID:
- Q92820
- Molecular Weight:
- 35964.045 Da
References
- 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. [17439143 ]
- General Function:
- Folic acid transporter activity
- Specific Function:
- Transports folate across the inner membranes of mitochondria.
- Gene Name:
- SLC25A32
- Uniprot ID:
- Q9H2D1
- Molecular Weight:
- 35406.83 Da
References
- 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. [17016423 ]
- General Function:
- Methotrexate transporter activity
- Specific Function:
- Has been shown to act both as an intestinal proton-coupled high-affinity folate transporter and as an intestinal heme transporter which mediates heme uptake from the gut lumen into duodenal epithelial cells. The iron is then released from heme and may be transported into the bloodstream. Dietary heme iron is an important nutritional source of iron. Shows a higher affinity for folate than heme.
- Gene Name:
- SLC46A1
- Uniprot ID:
- Q96NT5
- Molecular Weight:
- 49770.04 Da
References
- 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. [17616776 ]
- General Function:
- Receptor activity
- Specific 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. Required for normal embryonic development and normal cell proliferation.
- Gene Name:
- FOLR1
- Uniprot ID:
- P15328
- 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. [21879757 ]
- General Function:
- Thymidylate synthase activity
- Specific Function:
- Contributes to the de novo mitochondrial thymidylate biosynthesis pathway.
- Gene Name:
- TYMS
- Uniprot ID:
- P04818
- Molecular Weight:
- 35715.65 Da
References
- Brixner DI, Ueda T, Cheng YC, Hynes JB, Broom AD: Folate analogues as inhibitors of thymidylate synthase. J Med Chem. 1987 Apr;30(4):675-8. [3470522 ]
- General Function:
- Nadph binding
- Specific 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 DHFRL1.
- Gene Name:
- DHFR
- Uniprot ID:
- P00374
- Molecular Weight:
- 21452.61 Da
References
- Taira K, Benkovic SJ: Evaluation of the importance of hydrophobic interactions in drug binding to dihydrofolate reductase. J Med Chem. 1988 Jan;31(1):129-37. [3275776 ]
From T3DB