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Identification
Name Tetrahydrofolic acid
Accession Number DB00116 (NUTR00056)
Type small molecule
Groups approved, nutraceutical
Description

Tetrahydrofolic acid is a folic acid derivative. It is produced from dihydrofolic acid by dihydrofolate reductase.
It is converted into 5,10-methylenetetrahydrofolate by serine hydroxymethyltransferase. It is a coenzyme in many reactions, especially in the metabolism of amino acids and nucleic acids. It acts as a donor of a group with one carbon atom. It gets this carbon atom by sequestering formaldehyde produced in other processes.
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
5,6,7,8-tetrahydrofolate
5,6,7,8-tetrahydrofolic acid
tetrahydrofolate
Salts Not Available
Brand names Not Available
Brand mixtures Not Available
Categories
  • Dietary supplement
  • Micronutrient
CAS number 135-16-0
Weight Average: 445.4292
Monoisotopic: 445.170981503
Chemical Formula C19H23N7O6
InChI Key InChIKey=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
Plain Text
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
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Pterins
  • Keto-Acids
Substructures
  • Pterins
  • Hydroxy Compounds
  • Acetates
  • Aliphatic and Aryl Amines
  • Amino Ketones
  • Benzene and Derivatives
  • Carboxylic Acids and Derivatives
  • Pyrimidines and Derivatives
  • Heterocyclic compounds
  • Aromatic compounds
  • Keto-Acids
  • Carboxamides and Derivatives
  • Benzoyl Derivatives
  • Cyanamides
  • Benzamides
  • Anilines
Pharmacology
Indication For nutritional supplementation, also for treating dietary shortage or imbalance.
Pharmacodynamics 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.
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
Toxicity Not Available
Affected organisms
  • Humans and other mammals
Pathways Not Available
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 2.69e-01 g/l ALOGPS
logP -0.96 ALOGPS
logP -4.2 ChemAxon
logS -3.2 ALOGPS
pKa (strongest acidic) 3.51 ChemAxon
pKa (strongest basic) 3.58 ChemAxon
physiological charge -2 ChemAxon
hydrogen acceptor count 12 ChemAxon
hydrogen donor count 8 ChemAxon
polar surface area 207.27 ChemAxon
rotatable bond count 9 ChemAxon
refractivity 121.39 ChemAxon
polarizability 42.95 ChemAxon
References
Synthesis Reference Not Available
General Reference Not Available
External Links
Resource Link
KEGG Compound C00101 Link_out
PubChem Compound 91443 Link_out
PubChem Substance 46504756 Link_out
ChemSpider 82572 Link_out
ChEBI 20506 Link_out
ChEMBL 20506 Link_out
Therapeutic Targets Database DAP001308 Link_out
PharmGKB PA164745110 Link_out
HET THL Link_out
Wikipedia http://en.wikipedia.org/wiki/Tetrahydrofolic_acid Link_out
ATC Codes Not Available
AHFS Codes Not Available
PDB Entries
FDA label Not Available
MSDS Not Available
Interactions
Drug Interactions Not Available
Food Interactions Not Available
Targets

1. C-1-tetrahydrofolate synthase, cytoplasmic

Pharmacological action: unknown
Actions: cofactor
Organism class: human
UniProt ID: P11586 Link_out
Gene: MTHFD1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. 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. Pubmed
  2. 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. Pubmed
  3. 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. Pubmed
  4. 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. Pubmed
  5. 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. Pubmed

2. Bifunctional methylenetetrahydrofolate dehydrogenase/cyclohydrolase, mitochondrial

Pharmacological action: unknown
Actions: cofactor
Organism class: human
UniProt ID: P13995 Link_out
Gene: MTHFD2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. 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. Pubmed

3. Aminomethyltransferase, mitochondrial

Pharmacological action: unknown
Actions: cofactor

The glycine cleavage system catalyzes the degradation of glycine

Organism class: human
UniProt ID: P48728 Link_out
Gene: AMT Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. 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. Pubmed
  3. 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. Pubmed

4. AMT protein

Pharmacological action: unknown
Actions: cofactor
Organism class: human
UniProt ID: Q96IG6 Link_out
Gene: AMT Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Lee HH, Kim DJ, Ahn HJ, Ha JY, Suh SW: Crystal structure of T-protein of the glycine cleavage system. Cofactor binding, insights into H-protein recognition, and molecular basis for understanding nonketotic hyperglycinemia. J Biol Chem. 2004 Nov 26;279(48):50514-23. Epub 2004 Sep 7. Pubmed
  2. 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. Pubmed
  3. Scrutton NS, Leys D: Crystal structure of DMGO provides a prototype for a new tetrahydrofolate-binding fold. Biochem Soc Trans. 2005 Aug;33(Pt 4):776-9. Pubmed
  4. Gangjee A, Kurup S, Namjoshi O: Dihydrofolate reductase as a target for chemotherapy in parasites. Curr Pharm Des. 2007;13(6):609-39. Pubmed

5. 10-formyltetrahydrofolate dehydrogenase

Pharmacological action: unknown
Actions: cofactor

10-formyltetrahydrofolate + NADP(+) + H(2)O = tetrahydrofolate + CO(2) + NADPH

Organism class: human
UniProt ID: O75891 Link_out
Gene: ALDH1L1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. 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. Pubmed
  2. 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. Pubmed
  3. 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. Pubmed
  4. 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. Pubmed
  5. 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. Pubmed

6. Methionine synthase

Pharmacological action: unknown
Actions: cofactor
Organism class: human
UniProt ID: Q99707 Link_out
Gene: MTR Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. 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. Pubmed
  2. Fowler B: The folate cycle and disease in humans. Kidney Int Suppl. 2001 Feb;78:S221-9. Pubmed
  3. Fu TF, di Salvo M, Schirch V: Enzymatic determination of homocysteine in cell extracts. Anal Biochem. 2001 Mar;290(2):359-65. Pubmed
  4. 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. Pubmed
  5. 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. Pubmed

7. Formimidoyltransferase-cyclodeaminase

Pharmacological action: unknown
Actions: cofactor

Folate-dependent enzyme, that displays both transferase and deaminase activity. Serves to channel one-carbon units from formiminoglutamate to the folate pool

Organism class: human
UniProt ID: O95954 Link_out
Gene: FTCD Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Bashour AM, Bloom GS: 58K, a microtubule-binding Golgi protein, is a formiminotransferase cyclodeaminase. J Biol Chem. 1998 Jul 31;273(31):19612-7. Pubmed
  2. Cook RJ: Disruption of histidine catabolism in NEUT2 mice. Arch Biochem Biophys. 2001 Aug 15;392(2):226-32. Pubmed
  3. 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. Pubmed
  4. 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. Pubmed

8. Bifunctional purine biosynthesis protein PURH [Includes: Phosphoribosylaminoimidazolecarboxamide formyltransferase

Pharmacological action: unknown
Actions: cofactor

10-formyltetrahydrofolate + 5-amino-1-(5- phospho-D-ribosyl)imidazole-4-carboxamide = tetrahydrofolate + 5- formamido-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide

Organism class: human
UniProt ID: P31939 Link_out
Gene: ATIC Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. 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. Pubmed
  2. 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. Pubmed

9. Serine hydroxymethyltransferase, cytosolic

Pharmacological action: unknown
Actions: cofactor

Interconversion of serine and glycine

Organism class: human
UniProt ID: P34896 Link_out
Gene: SHMT1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. 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. Pubmed
  2. 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. Pubmed
  3. 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. Pubmed
  4. 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. Pubmed
  5. 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. Pubmed
  6. 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. Pubmed

10. Serine hydroxymethyltransferase, mitochondrial

Pharmacological action: unknown
Actions: cofactor

Interconversion of serine and glycine

Organism class: human
UniProt ID: P34897 Link_out
Gene: SHMT2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. 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. Pubmed
  2. 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. Pubmed
  3. 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. Pubmed
  4. 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. Pubmed
  5. 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. Pubmed

11. Methylenetetrahydrofolate reductase

Pharmacological action: unknown
Actions: cofactor

Catalyzes the conversion of 5,10- methylenetetrahydrofolate to 5-methyltetrahydrofolate, a co- substrate for homocysteine remethylation to methionine

Organism class: human
UniProt ID: P42898 Link_out
Gene: MTHFR Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. 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. Pubmed
  2. 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. Pubmed
  3. 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. Pubmed
  4. 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. Pubmed
  5. 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. Pubmed

12. Serine hydroxymethyltransferase 2

Pharmacological action: unknown
Actions: cofactor
Organism class: human
UniProt ID: Q53ET4 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA

References:
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. 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. Pubmed
  3. 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 Jul 30;. Pubmed

13. SHMT2 protein

Pharmacological action: unknown
Actions: cofactor
Organism class: human
UniProt ID: Q5BJF5 Link_out
Gene: SHMT2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. 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. Pubmed

14. Hypothetical protein DKFZp686P09201

Pharmacological action: unknown
Actions: cofactor
Organism class: human
UniProt ID: Q5HYG8 Link_out
Gene: DKFZp686P09201 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. 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. Pubmed

15. 5,10-methylenetetrahydrofolate reductase

Pharmacological action: unknown
Actions: cofactor
Organism class: human
UniProt ID: Q5SNW5 Link_out
Gene: MTHFR Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. 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. Pubmed
  3. 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. Pubmed
  4. 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. Pubmed
  5. 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. Pubmed

16. SHMT2 protein

Pharmacological action: unknown
Actions: cofactor
Organism class: human
UniProt ID: Q8N1A5 Link_out
Gene: SHMT2
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. 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. Pubmed
  2. 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. Pubmed
  3. 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. Pubmed
  4. 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. Pubmed
  5. 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. Pubmed

17. Methionyl-tRNA formyltransferase, mitochondrial

Pharmacological action: unknown
Actions: cofactor

Formylates methionyl-tRNA in mitochondria. A single tRNA(Met) gene gives rise to both an initiator and an elongator species via an unknown mechanism

Organism class: human
UniProt ID: Q96DP5 Link_out
Gene: MTFMT Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. 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. Pubmed

18. Methylenetetrahydrofolate reductase intermediate form

Pharmacological action: unknown
Actions: cofactor
Organism class: human
UniProt ID: Q9NY62 Link_out
Gene: MTHFR Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Dilley A, Hooper WC, El-Jamil M, Renshaw M, Wenger NK, Evatt BL: Mutations in the genes regulating methylene tetrahydrofolate reductase (MTHFR C—>T677) and cystathione beta-synthase (CBS G—>A919, CBS T—>c833) are not associated with myocardial infarction in African Americans. Thromb Res. 2001 Jul 15;103(2):109-15. Pubmed
  2. Huang L, Zhang J, Hayakawa T, Tsuge H: Assays of methylenetetrahydrofolate reductase and methionine synthase activities by monitoring 5-methyltetrahydrofolate and tetrahydrofolate using high-performance liquid chromatography with fluorescence detection. Anal Biochem. 2001 Dec 15;299(2):253-9. Pubmed
  3. 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. Pubmed
  4. Tsai AW, Cushman M, Tsai MY, Heckbert SR, Rosamond WD, Aleksic N, Yanez ND, Psaty BM, Folsom AR: Serum homocysteine, thermolabile variant of methylene tetrahydrofolate reductase (MTHFR), and venous thromboembolism: Longitudinal Investigation of Thromboembolism Etiology (LITE). Am J Hematol. 2003 Mar;72(3):192-200. Pubmed
  5. 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. Pubmed
Transporters

1. Canalicular multispecific organic anion transporter 1

Actions: inhibitor

Mediates hepatobiliary excretion of numerous organic anions. May function as a cellular cisplatin transporter

UniProt ID: Q92887 Link_out
Gene: ABCC2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. 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. Pubmed
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Drug created on June 13, 2005 07:24 / Updated on February 08, 2013 16:19