2.0 2012-05-31 13:47:53 -0600 2015-06-03 15:53:51 -0600 ECMDB01216 M2MDB000302 Tetrahydropteridine Tetrahydropteridine is a member of the chemical class known as Pteridines and Derivatives. These are polycyclic aromatic compounds containing a pteridine moiety, which consists of a pyrimidine fused to a pyrazine ring to form pyrimido(4,5-b)pyrazine. In a reversible reaction catalyzed by a nitroreductase / dihydropteridine reductase (EC 1.5.1.34), tetrahydropteridine can be converted to dihydropteridine while reducing NAD(P)+ to NAD(P)H. (KEGG) 5,6,7,8-Tetrahydro-Pteridine 5,6,7,8-Tetrahydropteridine H4-biopterin Tetrahydropteridine THP C6H8N4 136.1545 136.074896276 5,6,7,8-tetrahydropteridine 5,6,7,8-tetrahydropteridine 10593-78-9 C1CNC2=C(N1)C=NC=N2 InChI=1S/C6H8N4/c1-2-9-6-5(8-1)3-7-4-10-6/h3-4,8H,1-2H2,(H,7,9,10) IDAICLIJTRXNER-UHFFFAOYSA-N Solid Cytosol logp 0.29 ALOGPS logs -1.98 ALOGPS solubility 1.43e+00 g/l ALOGPS logp -0.58 ChemAxon pka_strongest_acidic 19.35 ChemAxon pka_strongest_basic 5.42 ChemAxon iupac 5,6,7,8-tetrahydropteridine ChemAxon average_mass 136.1545 ChemAxon mono_mass 136.074896276 ChemAxon smiles C1CNC2=C(N1)C=NC=N2 ChemAxon formula C6H8N4 ChemAxon inchi InChI=1S/C6H8N4/c1-2-9-6-5(8-1)3-7-4-10-6/h3-4,8H,1-2H2,(H,7,9,10) ChemAxon inchikey IDAICLIJTRXNER-UHFFFAOYSA-N ChemAxon polar_surface_area 49.84 ChemAxon refractivity 41.45 ChemAxon polarizability 13.53 ChemAxon rotatable_bond_count 0 ChemAxon acceptor_count 4 ChemAxon donor_count 2 ChemAxon physiological_charge 0 ChemAxon formal_charge 0 ChemAxon Folate biosynthesis The biosynthesis of folic acid begins with a product of purine nucleotides de novo biosynthesis pathway, GTP. This compound is involved in a reaction with water through a GTP cyclohydrolase 1 protein complex, resulting in a hydrogen ion, formic acid and 7,8-dihydroneopterin 3-triphosphate. The latter compound is dephosphatased through a dihydroneopterin triphosphate pyrophosphohydrolase resulting in the release of a pyrophosphate, hydrogen ion and 7,8-dihydroneopterin 3-phosphate. The latter compound reacts with water spontaneously resulting in the release of a phosphate and a 7,8 -dihydroneopterin. This compound reacts with a dihydroneopterin aldolase, releasing a glycoaldehyde and 6-hydroxymethyl-7,9-dihydropterin. The latter compound is phosphorylated with a ATP-driven 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase resulting in a (2-amino-4-hydroxy-7,8-dihydropteridin-6-yl)methyl diphosphate. Chorismate is metabolized by reacting with L-glutamine through a 4-amino-4-deoxychorismate synthase resulting in L-glutamic acid and 4-amino-4-deoxychorismate. The latter compound then reacts through an aminodeoxychorismate lyase resulting in pyruvic acid,hydrogen ion and p-aminobenzoic acid. (2-amino-4-hydroxy-7,8-dihydropteridin-6-yl)methyl diphosphate and p-aminobenzoic acid react through a dihydropteroate synthase resulting in pyrophosphate and 7,8-dihydropteroic acid. This compound reacts with L-glutamic acid through an ATP driven bifunctional folylpolyglutamate synthetase / dihydrofolate synthetase resulting in a 7,8-dihydrofolate monoglutamate. This compound is reduced through an NADPH mediated dihydrofolate reductase resulting in a tetrahydrofate. This product goes on to a one carbon pool by folate pathway. PW000908 ec00790 Metabolic Trinitrotoluene degradation ec00633 Metabolic pathways eco01100 Specdb::CMs 16404 Specdb::CMs 153901 Specdb::NmrOneD 87572 Specdb::NmrOneD 87573 Specdb::NmrOneD 87574 Specdb::NmrOneD 87575 Specdb::NmrOneD 87576 Specdb::NmrOneD 87577 Specdb::NmrOneD 87578 Specdb::NmrOneD 87579 Specdb::NmrOneD 87580 Specdb::NmrOneD 87581 Specdb::NmrOneD 87582 Specdb::NmrOneD 87583 Specdb::NmrOneD 87584 Specdb::NmrOneD 87585 Specdb::NmrOneD 87586 Specdb::NmrOneD 87587 Specdb::NmrOneD 87588 Specdb::NmrOneD 87589 Specdb::NmrOneD 87590 Specdb::NmrOneD 87591 Specdb::MsMs 28694 Specdb::MsMs 28695 Specdb::MsMs 28696 Specdb::MsMs 35252 Specdb::MsMs 35253 Specdb::MsMs 35254 Specdb::MsMs 2785786 Specdb::MsMs 2785787 Specdb::MsMs 2785788 Specdb::MsMs 2922646 Specdb::MsMs 2922647 Specdb::MsMs 2922648 HMDB01216 156 151 C05650 28889 5678-TETRAHYDROPTERIDINE Keseler, I. M., Collado-Vides, J., Santos-Zavaleta, A., Peralta-Gil, M., Gama-Castro, S., Muniz-Rascado, L., Bonavides-Martinez, C., Paley, S., Krummenacker, M., Altman, T., Kaipa, P., Spaulding, A., Pacheco, J., Latendresse, M., Fulcher, C., Sarker, M., Shearer, A. G., Mackie, A., Paulsen, I., Gunsalus, R. P., Karp, P. D. (2011). "EcoCyc: a comprehensive database of Escherichia coli biology." Nucleic Acids Res 39:D583-D590. 21097882 Kanehisa, M., Goto, S., Sato, Y., Furumichi, M., Tanabe, M. (2012). "KEGG for integration and interpretation of large-scale molecular data sets." Nucleic Acids Res 40:D109-D114. 22080510 van der Werf, M. J., Overkamp, K. M., Muilwijk, B., Coulier, L., Hankemeier, T. (2007). "Microbial metabolomics: toward a platform with full metabolome coverage." Anal Biochem 370:17-25. 17765195 Winder, C. L., Dunn, W. B., Schuler, S., Broadhurst, D., Jarvis, R., Stephens, G. M., Goodacre, R. (2008). "Global metabolic profiling of Escherichia coli cultures: an evaluation of methods for quenching and extraction of intracellular metabolites." Anal Chem 80:2939-2948. 18331064 Rao GN, Cotlier E: The enzymatic activities of GTP cyclohydrolase, sepiapterin reductase, dihydropteridine reductase and dihydrofolate reductase; and tetrahydrobiopterin content in mammalian ocular tissues and in human senile cataracts. Comp Biochem Physiol B. 1985;80(1):61-6. 3881214 Werner ER, Hermetter A, Prast H, Golderer G, Werner-Felmayer G: Widespread occurrence of glyceryl ether monooxygenase activity in rat tissues detected by a novel assay. J Lipid Res. 2007 Jun;48(6):1422-7. Epub 2007 Feb 15. 17303893 Hoffman DR, Hoffman LH, Snyder F: Cytotoxicity and metabolism of alkyl phospholipid analogues in neoplastic cells. Cancer Res. 1986 Nov;46(11):5803-9. 3756924 Thoeni G, Werner ER, Werner-Felmayer G: Tetrahydropteridines suppress gene expression and induce apoptosis of activated RAW264.7 cells via formation of hydrogen peroxide. Free Radic Biol Med. 2004 Aug 1;37(3):375-85. 15223071 Flavohemoprotein P24232 HMP_ECOLI hmp http://ecmdb.ca/proteins/P24232.xml Oxygen-insensitive NAD(P)H nitroreductase P38489 NFNB_ECOLI nfnB http://ecmdb.ca/proteins/P38489.xml 6,7-Dihydropteridine + 3 Hydrogen ion + NADH <> NAD + Tetrahydropteridine 6,7-Dihydropteridine + 3 Hydrogen ion + NADPH <> NADP + Tetrahydropteridine NAD(P)⁺ + Tetrahydropteridine <> NAD(P)H + 6,7-Dihydropteridine + Hydrogen ion 1.5.1.34-RXN Tetrahydropteridine + NAD > 6,7-Dihydropteridine + NADH Tetrahydropteridine + NADP > 6,7-Dihydropteridine + NADPH Tetrahydropteridine + NAD + NADP <> 6,7-Dihydropteridine + NADH + NADPH + Hydrogen ion R07354 R07355