Explore a selection of our essential drug information below, or:
Identification
- Generic Name
- Tetrahydrofolic acid
- DrugBank Accession Number
- DB00116
- Background
Tetrahydrofolic acid is a folic acid derivative that is produced from dihydrofolic acid after conversion by dihydrofolate reductase. It is converted into 5,10-methylenetetrahydrofolate by serine hydroxymethyltransferase. It is a soluble coenzyme in many reactions, especially in the metabolism of amino acids and nucleic acids.
- Type
- Small Molecule
- Groups
- Nutraceutical
- Structure
Structure for Tetrahydrofolic acid (DB00116)
- Weight
- Average: 445.4292
Monoisotopic: 445.170981503 - Chemical Formula
- C19H23N7O6
- Synonyms
- 5,6,7,8-tetrahydrofolate
- 5,6,7,8-tetrahydrofolic acid
- Tetrahydrofolate
Pharmacology
- Indication
For nutritional supplementation, also for treating dietary shortage or imbalance.
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Tetrahydrofolate is the main active metabolite of dietary folate. It is vital as a coenzyme in reactions involving transfers of single carbon groups. Tetrahydrofolate has a role in nucleic and amino acid synthesis. As nucleic and amino acid synthesis is affected by a deficiency of tetrahydrofolate, actively dividing and growing cells tend to be the first affected. Tetrahydrofolate is used to treat topical sprue and megaloblastic and macrocytic anemias, hematologic complications resulting from a deficiency in folic acid.
- Mechanism of action
Tetrahydrofolate is transported across cells by receptor-mediated endocytosis where it is needed to maintain normal erythropoiesis, synthesize purine and thymidylate nucleic acids, interconvert amino acids, methylate tRNA, and generate and use formate.
Target Actions Organism UC-1-tetrahydrofolate synthase, cytoplasmic cofactorHumans UBifunctional methylenetetrahydrofolate dehydrogenase/cyclohydrolase, mitochondrial cofactorHumans UAminomethyltransferase, mitochondrial cofactorHumans UCytosolic 10-formyltetrahydrofolate dehydrogenase cofactorHumans UMethionine synthase cofactorHumans UFormimidoyltransferase-cyclodeaminase cofactorHumans UBifunctional purine biosynthesis protein ATIC cofactorHumans USerine hydroxymethyltransferase, cytosolic cofactorHumans USerine hydroxymethyltransferase, mitochondrial cofactorHumans UMethylenetetrahydrofolate reductase (NADPH) cofactorHumans USerine hydroxymethyltransferase cofactorHumans UMethionyl-tRNA formyltransferase, mitochondrial cofactorHumans - Absorption
Not Available
- Volume of distribution
Not Available
- Protein binding
Not Available
- Metabolism
- Not Available
- Route of elimination
Not Available
- Half-life
Not Available
- 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
Not Available
- Pathways
- 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 Tetrahydrofolic acid is combined with Capecitabine. Carbamazepine The serum concentration of Tetrahydrofolic acid can be decreased when it is combined with Carbamazepine. Colestipol The serum concentration of Tetrahydrofolic acid can be decreased when it is combined with Colestipol. Cycloguanil The therapeutic efficacy of Cycloguanil can be decreased when used in combination with Tetrahydrofolic acid. Dapsone The therapeutic efficacy of Dapsone can be decreased when used in combination with Tetrahydrofolic acid. - Food Interactions
- Not Available
Categories
- Drug Categories
- 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
- Hippuric acids / N-acyl-alpha amino acids / Pterins and derivatives / Aminobenzamides / Aniline and substituted anilines / Benzoyl derivatives / Phenylalkylamines / Hydroxypyrimidines / Secondary alkylarylamines / Dicarboxylic acids and derivatives show 9 more
- Substituents
- Amine / Amino acid / Aminobenzamide / Aminobenzoic acid or derivatives / Aniline or substituted anilines / Aromatic heteropolycyclic compound / Azacycle / Benzamide / Benzenoid / Benzoic acid or derivatives show 28 more
- Molecular Framework
- Aromatic heteropolycyclic compounds
- External Descriptors
- tetrahydrofolic acid (CHEBI:20506)
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- 43ZWB253H4
- CAS number
- 135-16-0
- InChI Key
- MSTNYGQPCMXVAQ-KIYNQFGBSA-N
- InChI
- InChI=1S/C19H23N7O6/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/h1-4,11-12,21,23H,5-8H2,(H,24,29)(H,27,28)(H,31,32)(H4,20,22,25,26,30)/t11?,12-/m0/s1
- IUPAC Name
- (2S)-2-[(4-{[(2-amino-4-oxo-1,4,5,6,7,8-hexahydropteridin-6-yl)methyl]amino}phenyl)formamido]pentanedioic acid
- SMILES
- NC1=NC(=O)C2=C(NCC(CNC3=CC=C(C=C3)C(=O)N[C@@H](CCC(O)=O)C(O)=O)N2)N1
References
- Synthesis Reference
Attilio Melera, Fabrizio Marazza, "Process for the preparation of alkaline earth metal salts of (6R)-N(10)-formyl-5,6,7,8-tetrahydrofolic acid." U.S. Patent US5332815, issued May, 1954.
US5332815- General References
- Not Available
- External Links
- Human Metabolome Database
- HMDB0304496
- KEGG Compound
- C00101
- PubChem Compound
- 91443
- PubChem Substance
- 46504756
- ChemSpider
- 82572
- BindingDB
- 50022833
- ChEBI
- 20506
- ChEMBL
- CHEMBL2021342
- Therapeutic Targets Database
- DAP001308
- PharmGKB
- PA164745110
- Wikipedia
- Tetrahydrofolic_acid
Clinical Trials
- Clinical Trials
Clinical Trial & Rare Diseases Add-on Data Package
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Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
- Not Available
- Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
Property Value Source logP -2.7 Not Available - Predicted Properties
Property Value Source Water Solubility 0.269 mg/mL ALOGPS logP -0.96 ALOGPS logP -3.4 Chemaxon logS -3.2 ALOGPS pKa (Strongest Acidic) 3.21 Chemaxon pKa (Strongest Basic) 5.33 Chemaxon Physiological Charge -2 Chemaxon Hydrogen Acceptor Count 12 Chemaxon Hydrogen Donor Count 8 Chemaxon Polar Surface Area 207.27 Å2 Chemaxon Rotatable Bond Count 9 Chemaxon Refractivity 121.39 m3·mol-1 Chemaxon Polarizability 42.95 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 - 0.5181 Blood Brain Barrier - 0.533 Caco-2 permeable - 0.8443 P-glycoprotein substrate Substrate 0.7509 P-glycoprotein inhibitor I Non-inhibitor 0.972 P-glycoprotein inhibitor II Non-inhibitor 0.9966 Renal organic cation transporter Non-inhibitor 0.8752 CYP450 2C9 substrate Non-substrate 0.8058 CYP450 2D6 substrate Non-substrate 0.7984 CYP450 3A4 substrate Non-substrate 0.637 CYP450 1A2 substrate Non-inhibitor 0.9344 CYP450 2C9 inhibitor Non-inhibitor 0.9265 CYP450 2D6 inhibitor Non-inhibitor 0.9437 CYP450 2C19 inhibitor Non-inhibitor 0.9215 CYP450 3A4 inhibitor Non-inhibitor 0.9161 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.9631 Ames test Non AMES toxic 0.8293 Carcinogenicity Non-carcinogens 0.954 Biodegradation Not ready biodegradable 0.8759 Rat acute toxicity 2.4563 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.9534 hERG inhibition (predictor II) Non-inhibitor 0.6623
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS splash10-0002-0090300000-c66445bc20ac1f82390b Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS splash10-002f-0002900000-35b628373d45ea988124 Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS splash10-0002-0491100000-f9ef32fa86548c9631c8 Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS splash10-0f7p-1907500000-628c8741ff9fb2d296a7 Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS splash10-014i-0933000000-b0059c0e5794f5354d85 Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS splash10-0udl-4916500000-4af506f14ea619ef144f 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]- 195.76189 predictedDeepCCS 1.0 (2019) [M+H]+ 198.13258 predictedDeepCCS 1.0 (2019) [M+Na]+ 204.21303 predictedDeepCCS 1.0 (2019)
Targets
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- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Cofactor
- General Function
- Trifunctional enzyme that catalyzes the interconversion of three forms of one-carbon-substituted tetrahydrofolate: (6R)-5,10-methylene-5,6,7,8-tetrahydrofolate, 5,10-methenyltetrahydrofolate and (6S)-10-formyltetrahydrofolate (PubMed:10828945, PubMed:18767138, PubMed:1881876). These derivatives of tetrahydrofolate are differentially required in nucleotide and amino acid biosynthesis, (6S)-10-formyltetrahydrofolate being required for purine biosynthesis while (6R)-5,10-methylene-5,6,7,8-tetrahydrofolate is used for serine and methionine biosynthesis for instance (PubMed:18767138, PubMed:25633902)
- Specific Function
- ATP binding
- Gene Name
- MTHFD1
- Uniprot ID
- P11586
- Uniprot Name
- C-1-tetrahydrofolate synthase, cytoplasmic
- Molecular Weight
- 101530.36 Da
References
- Akar N, Akar E, Ozel D, Deda G, Sipahi T: Common mutations at the homocysteine metabolism pathway and pediatric stroke. Thromb Res. 2001 Apr 15;102(2):115-20. [Article]
- Walkup AS, Appling DR: Enzymatic characterization of human mitochondrial C1-tetrahydrofolate synthase. Arch Biochem Biophys. 2005 Oct 15;442(2):196-205. Epub 2005 Aug 30. [Article]
- Matakidou A, El Galta R, Rudd MF, Webb EL, Bridle H, Eisen T, Houlston RS: Prognostic significance of folate metabolism polymorphisms for lung cancer. Br J Cancer. 2007 Jul 16;97(2):247-52. Epub 2007 May 29. [Article]
- Salmassi TM, Leadbetter JR: Analysis of genes of tetrahydrofolate-dependent metabolism from cultivated spirochaetes and the gut community of the termite Zootermopsis angusticollis. Microbiology. 2003 Sep;149(Pt 9):2529-37. [Article]
- Prasannan P, Pike S, Peng K, Shane B, Appling DR: Human mitochondrial C1-tetrahydrofolate synthase: gene structure, tissue distribution of the mRNA, and immunolocalization in Chinese hamster ovary calls. J Biol Chem. 2003 Oct 31;278(44):43178-87. Epub 2003 Aug 22. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Cofactor
- General Function
- Although its dehydrogenase activity is NAD-specific, it can also utilize NADP at a reduced efficiency
- Specific Function
- magnesium ion binding
- Gene Name
- MTHFD2
- Uniprot ID
- P13995
- Uniprot Name
- Bifunctional methylenetetrahydrofolate dehydrogenase/cyclohydrolase, mitochondrial
- Molecular Weight
- 37894.775 Da
References
- Salmassi TM, Leadbetter JR: Analysis of genes of tetrahydrofolate-dependent metabolism from cultivated spirochaetes and the gut community of the termite Zootermopsis angusticollis. Microbiology. 2003 Sep;149(Pt 9):2529-37. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Cofactor
- General Function
- The glycine cleavage system catalyzes the degradation of glycine
- Specific Function
- aminomethyltransferase activity
- Gene Name
- AMT
- Uniprot ID
- P48728
- Uniprot Name
- Aminomethyltransferase, mitochondrial
- Molecular Weight
- 43945.65 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]
- Masai E, Sasaki M, Minakawa Y, Abe T, Sonoki T, Miyauchi K, Katayama Y, Fukuda M: A novel tetrahydrofolate-dependent O-demethylase gene is essential for growth of Sphingomonas paucimobilis SYK-6 with syringate. J Bacteriol. 2004 May;186(9):2757-65. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Cofactor
- General Function
- Cytosolic 10-formyltetrahydrofolate dehydrogenase that catalyzes the NADP(+)-dependent conversion of 10-formyltetrahydrofolate to tetrahydrofolate and carbon dioxide (PubMed:19933275, PubMed:21238436). May also have an NADP(+)-dependent aldehyde dehydrogenase activity towards formaldehyde, acetaldehyde, propionaldehyde, and benzaldehyde (By similarity)
- Specific Function
- aldehyde dehydrogenase (NAD+) activity
- Gene Name
- ALDH1L1
- Uniprot ID
- O75891
- Uniprot Name
- Cytosolic 10-formyltetrahydrofolate dehydrogenase
- Molecular Weight
- 98828.505 Da
References
- Fu TF, Maras B, Barra D, Schirch V: A noncatalytic tetrahydrofolate tight binding site is on the small domain of 10-formyltetrahydrofolate dehydrogenase. Arch Biochem Biophys. 1999 Jul 15;367(2):161-6. [Article]
- Krupenko SA, Wagner C: Aspartate 142 is involved in both hydrolase and dehydrogenase catalytic centers of 10-formyltetrahydrofolate dehydrogenase. J Biol Chem. 1999 Dec 10;274(50):35777-84. [Article]
- Krupenko SA, Vlasov AP, Wagner C: On the role of conserved histidine 106 in 10-formyltetrahydrofolate dehydrogenase catalysis: connection between hydrolase and dehydrogenase mechanisms. J Biol Chem. 2001 Jun 29;276(26):24030-7. Epub 2001 Apr 24. [Article]
- Anguera MC, Field MS, Perry C, Ghandour H, Chiang EP, Selhub J, Shane B, Stover PJ: Regulation of folate-mediated one-carbon metabolism by 10-formyltetrahydrofolate dehydrogenase. J Biol Chem. 2006 Jul 7;281(27):18335-42. Epub 2006 Apr 20. [Article]
- Oleinik NV, Krupenko NI, Reuland SN, Krupenko SA: Leucovorin-induced resistance against FDH growth suppressor effects occurs through DHFR up-regulation. Biochem Pharmacol. 2006 Jul 14;72(2):256-66. Epub 2006 Apr 25. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Cofactor
- 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
- Hall DA, Jordan-Starck TC, Loo RO, Ludwig ML, Matthews RG: Interaction of flavodoxin with cobalamin-dependent methionine synthase. Biochemistry. 2000 Sep 5;39(35):10711-9. [Article]
- Fowler B: The folate cycle and disease in humans. Kidney Int Suppl. 2001 Feb;78:S221-9. [Article]
- Fu TF, di Salvo M, Schirch V: Enzymatic determination of homocysteine in cell extracts. Anal Biochem. 2001 Mar;290(2):359-65. [Article]
- Jarrett JT, Choi CY, Matthews RG: Changes in protonation associated with substrate binding and Cob(I)alamin formation in cobalamin-dependent methionine synthase. Biochemistry. 1997 Dec 16;36(50):15739-48. [Article]
- Jarrett JT, Hoover DM, Ludwig ML, Matthews RG: The mechanism of adenosylmethionine-dependent activation of methionine synthase: a rapid kinetic analysis of intermediates in reductive methylation of Cob(II)alamin enzyme. Biochemistry. 1998 Sep 8;37(36):12649-58. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Cofactor
- General Function
- Folate-dependent enzyme, that displays both transferase and deaminase activity. Serves to channel one-carbon units from formiminoglutamate to the folate pool
- Specific Function
- folic acid binding
- Gene Name
- FTCD
- Uniprot ID
- O95954
- Uniprot Name
- Formimidoyltransferase-cyclodeaminase
- Molecular Weight
- 58925.93 Da
References
- Bashour AM, Bloom GS: 58K, a microtubule-binding Golgi protein, is a formiminotransferase cyclodeaminase. J Biol Chem. 1998 Jul 31;273(31):19612-7. [Article]
- Cook RJ: Disruption of histidine catabolism in NEUT2 mice. Arch Biochem Biophys. 2001 Aug 15;392(2):226-32. [Article]
- Kohls D, Croteau N, Mejia N, MacKenzie RE, Vrielink A: Crystallization and preliminary X-ray analysis of the formiminotransferase domain from the bifunctional enzyme formiminotransferase-cyclodeaminase. Acta Crystallogr D Biol Crystallogr. 1999 Jun;55(Pt 6):1206-8. [Article]
- Kohls D, Sulea T, Purisima EO, MacKenzie RE, Vrielink A: The crystal structure of the formiminotransferase domain of formiminotransferase-cyclodeaminase: implications for substrate channeling in a bifunctional enzyme. Structure. 2000 Jan 15;8(1):35-46. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Cofactor
- General Function
- Bifunctional enzyme that catalyzes the last two steps of purine biosynthesis (PubMed:11948179, PubMed:14756554). Acts as a transformylase that incorporates a formyl group to the AMP analog AICAR (5-amino-1-(5-phospho-beta-D-ribosyl)imidazole-4-carboxamide) to produce the intermediate formyl-AICAR (FAICAR) (PubMed:10985775, PubMed:11948179, PubMed:9378707). Can use both 10-formyldihydrofolate and 10-formyltetrahydrofolate as the formyl donor in this reaction (PubMed:10985775). Also catalyzes the cyclization of FAICAR to IMP (PubMed:11948179, PubMed:14756554). Is able to convert thio-AICAR to 6-mercaptopurine ribonucleotide, an inhibitor of purine biosynthesis used in the treatment of human leukemias (PubMed:10985775). Promotes insulin receptor/INSR autophosphorylation and is involved in INSR internalization (PubMed:25687571)
- Specific Function
- cadherin binding
- Gene Name
- ATIC
- Uniprot ID
- P31939
- Uniprot Name
- Bifunctional purine biosynthesis protein ATIC
- Molecular Weight
- 64615.255 Da
References
- Wolan DW, Greasley SE, Wall MJ, Benkovic SJ, Wilson IA: Structure of avian AICAR transformylase with a multisubstrate adduct inhibitor beta-DADF identifies the folate binding site. Biochemistry. 2003 Sep 23;42(37):10904-14. [Article]
- Bulock KG, Beardsley GP, Anderson KS: The kinetic mechanism of the human bifunctional enzyme ATIC (5-amino-4-imidazolecarboxamide ribonucleotide transformylase/inosine 5'-monophosphate cyclohydrolase). A surprising lack of substrate channeling. J Biol Chem. 2002 Jun 21;277(25):22168-74. Epub 2002 Apr 10. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Cofactor
- General Function
- Interconversion of serine and glycine (PubMed:24698160, PubMed:8505317)
- Specific Function
- aldehyde-lyase activity
- Gene Name
- SHMT1
- Uniprot ID
- P34896
- Uniprot Name
- Serine hydroxymethyltransferase, cytosolic
- Molecular Weight
- 53082.18 Da
References
- Scarsdale JN, Radaev S, Kazanina G, Schirch V, Wright HT: Crystal structure at 2.4 A resolution of E. coli serine hydroxymethyltransferase in complex with glycine substrate and 5-formyl tetrahydrofolate. J Mol Biol. 2000 Feb 11;296(1):155-68. [Article]
- Rao JV, Prakash V, Rao NA, Savithri HS: The role of Glu74 and Tyr82 in the reaction catalyzed by sheep liver cytosolic serine hydroxymethyltransferase. Eur J Biochem. 2000 Oct;267(19):5967-76. [Article]
- Heil SG, Van der Put NM, Waas ET, den Heijer M, Trijbels FJ, Blom HJ: Is mutated serine hydroxymethyltransferase (SHMT) involved in the etiology of neural tube defects? Mol Genet Metab. 2001 Jun;73(2):164-72. [Article]
- Ravanel S, Cherest H, Jabrin S, Grunwald D, Surdin-Kerjan Y, Douce R, Rebeille F: Tetrahydrofolate biosynthesis in plants: molecular and functional characterization of dihydrofolate synthetase and three isoforms of folylpolyglutamate synthetase in Arabidopsis thaliana. Proc Natl Acad Sci U S A. 2001 Dec 18;98(26):15360-5. [Article]
- Li R, Moore M, King J: Investigating the regulation of one-carbon metabolism in Arabidopsis thaliana. Plant Cell Physiol. 2003 Mar;44(3):233-41. [Article]
- Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Cofactor
- General Function
- Catalyzes the cleavage of serine to glycine accompanied with the production of 5,10-methylenetetrahydrofolate, an essential intermediate for purine biosynthesis (PubMed:24075985, PubMed:25619277, PubMed:29364879, PubMed:33015733). Serine provides the major source of folate one-carbon in cells by catalyzing the transfer of one carbon from serine to tetrahydrofolate (PubMed:25619277). Contributes to the de novo mitochondrial thymidylate biosynthesis pathway via its role in glycine and tetrahydrofolate metabolism: thymidylate biosynthesis is required to prevent uracil accumulation in mtDNA (PubMed:21876188). Also required for mitochondrial translation by producing 5,10-methylenetetrahydrofolate; 5,10-methylenetetrahydrofolate providing methyl donors to produce the taurinomethyluridine base at the wobble position of some mitochondrial tRNAs (PubMed:29364879, PubMed:29452640). Associates with mitochondrial DNA (PubMed:18063578). In addition to its role in mitochondria, also plays a role in the deubiquitination of target proteins as component of the BRISC complex: required for IFNAR1 deubiquitination by the BRISC complex (PubMed:24075985)
- Specific Function
- amino acid binding
- Gene Name
- SHMT2
- Uniprot ID
- P34897
- Uniprot Name
- Serine hydroxymethyltransferase, mitochondrial
- Molecular Weight
- 55992.385 Da
References
- Heil SG, Van der Put NM, Waas ET, den Heijer M, Trijbels FJ, Blom HJ: Is mutated serine hydroxymethyltransferase (SHMT) involved in the etiology of neural tube defects? Mol Genet Metab. 2001 Jun;73(2):164-72. [Article]
- Contestabile R, Paiardini A, Pascarella S, di Salvo ML, D'Aguanno S, Bossa F: l-Threonine aldolase, serine hydroxymethyltransferase and fungal alanine racemase. A subgroup of strictly related enzymes specialized for different functions. Eur J Biochem. 2001 Dec;268(24):6508-25. [Article]
- Li R, Moore M, King J: Investigating the regulation of one-carbon metabolism in Arabidopsis thaliana. Plant Cell Physiol. 2003 Mar;44(3):233-41. [Article]
- Appaji Rao N, Ambili M, Jala VR, Subramanya HS, Savithri HS: Structure-function relationship in serine hydroxymethyltransferase. Biochim Biophys Acta. 2003 Apr 11;1647(1-2):24-9. [Article]
- Angelaccio S, Chiaraluce R, Consalvi V, Buchenau B, Giangiacomo L, Bossa F, Contestabile R: Catalytic and thermodynamic properties of tetrahydromethanopterin-dependent serine hydroxymethyltransferase from Methanococcus jannaschii. J Biol Chem. 2003 Oct 24;278(43):41789-97. Epub 2003 Aug 5. [Article]
- Prabhu V, Chatson KB, Lui H, Abrams GD, King J: Effects of sulfanilamide and methotrexate on 13C fluxes through the glycine decarboxylase/serine hydroxymethyltransferase enzyme system in arabidopsis. Plant Physiol. 1998 Jan;116(1):137-44. [Article]
- Rajaram V, Bhavani BS, Kaul P, Prakash V, Appaji Rao N, Savithri HS, Murthy MR: Structure determination and biochemical studies on Bacillus stearothermophilus E53Q serine hydroxymethyltransferase and its complexes provide insights on function and enzyme memory. FEBS J. 2007 Aug;274(16):4148-60. Epub 2007 Jul 25. [Article]
- Vatsyayan R, Roy U: Molecular cloning and biochemical characterization of Leishmania donovani serine hydroxymethyltransferase. Protein Expr Purif. 2007 Apr;52(2):433-40. Epub 2006 Oct 26. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Cofactor
- 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
- Ubbink JB, Christianson A, Bester MJ, Van Allen MI, Venter PA, Delport R, Blom HJ, van der Merwe A, Potgieter H, Vermaak WJ: Folate status, homocysteine metabolism, and methylene tetrahydrofolate reductase genotype in rural South African blacks with a history of pregnancy complicated by neural tube defects. Metabolism. 1999 Feb;48(2):269-74. [Article]
- Heijmans BT, Gussekloo J, Kluft C, Droog S, Lagaay AM, Knook DL, Westendorp RG, Slagboom EP: Mortality risk in men is associated with a common mutation in the methylene-tetrahydrofolate reductase gene (MTHFR). Eur J Hum Genet. 1999 Feb-Mar;7(2):197-204. [Article]
- Tsai MY, Welge BG, Hanson NQ, Bignell MK, Vessey J, Schwichtenberg K, Yang F, Bullemer FE, Rasmussen R, Graham KJ: Genetic causes of mild hyperhomocysteinemia in patients with premature occlusive coronary artery diseases. Atherosclerosis. 1999 Mar;143(1):163-70. [Article]
- Holmes ZR, Regan L, Chilcott I, Cohen H: The C677T MTHFR gene mutation is not predictive of risk for recurrent fetal loss. Br J Haematol. 1999 Apr;105(1):98-101. [Article]
- Larsson J, Hultberg B, Hillarp A: Hyperhomocysteinemia and the MTHFR C677T mutation in central retinal vein occlusion. Acta Ophthalmol Scand. 2000 Jun;78(3):340-3. [Article]
- Siva A, De Lange M, Clayton D, Monteith S, Spector T, Brown MJ: The heritability of plasma homocysteine, and the influence of genetic variation in the homocysteine methylation pathway. QJM. 2007 Aug;100(8):495-9. Epub 2007 Jul 17. [Article]
- Leopardi P, Marcon F, Caiola S, Cafolla A, Siniscalchi E, Zijno A, Crebelli R: Effects of folic acid deficiency and MTHFR C677T polymorphism on spontaneous and radiation-induced micronuclei in human lymphocytes. Mutagenesis. 2006 Sep;21(5):327-33. Epub 2006 Sep 1. [Article]
- Ott K, Vogelsang H, Marton N, Becker K, Lordick F, Kobl M, Schuhmacher C, Novotny A, Mueller J, Fink U, Ulm K, Siewert JR, Hofler H, Keller G: The thymidylate synthase tandem repeat promoter polymorphism: A predictor for tumor-related survival in neoadjuvant treated locally advanced gastric cancer. Int J Cancer. 2006 Dec 15;119(12):2885-94. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Cofactor
- General Function
- Interconversion of serine and glycine.
- Specific Function
- cobalt ion binding
- Gene Name
- Not Available
- Uniprot ID
- Q53ET4
- Uniprot Name
- Serine hydroxymethyltransferase
- Molecular Weight
- 55973.345 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]
- Chang WN, Tsai JN, Chen BH, Huang HS, Fu TF: Serine hydroxymethyltransferase isoforms are differentially inhibited by leucovorin: characterization and comparison of recombinant zebrafish serine hydroxymethyltransferases. Drug Metab Dispos. 2007 Nov;35(11):2127-37. doi: 10.1124/dmd.107.016840. Epub 2007 Jul 30. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Cofactor
- General Function
- Methionyl-tRNA formyltransferase that formylates methionyl-tRNA in mitochondria and is crucial for translation initiation
- Specific Function
- methionyl-tRNA formyltransferase activity
- Gene Name
- MTFMT
- Uniprot ID
- Q96DP5
- Uniprot Name
- Methionyl-tRNA formyltransferase, mitochondrial
- Molecular Weight
- 43831.73 Da
References
- Li Y, Holmes WB, Appling DR, RajBhandary UL: Initiation of protein synthesis in Saccharomyces cerevisiae mitochondria without formylation of the initiator tRNA. J Bacteriol. 2000 May;182(10):2886-92. [Article]
Transporters
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- 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. Transports a wide variety of conjugated organic anions such as sulfate-, glucuronide- and glutathione (GSH)-conjugates of endo- and xenobiotics substrates (PubMed:10220572, PubMed:10421658, PubMed:11500505, PubMed:16332456). Mediates hepatobiliary excretion of mono- and bis-glucuronidated bilirubin molecules and therefore play an important role in bilirubin detoxification (PubMed:10421658). Mediates also hepatobiliary excretion of others glucuronide conjugates such as 17beta-estradiol 17-glucosiduronic acid and leukotriene C4 (PubMed:11500505). Transports sulfated bile salt such as taurolithocholate sulfate (PubMed:16332456). Transports various anticancer drugs, such as anthracycline, vinca alkaloid and methotrexate and HIV-drugs such as protease inhibitors (PubMed:10220572, PubMed:11500505, PubMed:12441801). Confers resistance to several anti-cancer drugs including cisplatin, doxorubicin, epirubicin, methotrexate, etoposide and vincristine (PubMed:10220572, PubMed:11500505)
- Specific Function
- ABC-type glutathione S-conjugate transporter activity
- Gene Name
- ABCC2
- Uniprot ID
- Q92887
- Uniprot Name
- ATP-binding cassette sub-family C member 2
- Molecular Weight
- 174205.64 Da
References
- Kusuhara H, Han YH, Shimoda M, Kokue E, Suzuki H, Sugiyama Y: Reduced folate derivatives are endogenous substrates for cMOAT in rats. Am J Physiol. 1998 Oct;275(4 Pt 1):G789-96. [Article]
Drug created at June 13, 2005 13:24 / Updated at August 02, 2024 07:21