2.0 2012-05-31 09:56:44 -0600 2015-09-13 12:56:05 -0600 ECMDB00076 M2MDB000027 Dihydrouracil Dihydrohuracil is an intermediate breakdown product of uracil. Dihydropyrimidine dehydrogenase catalyzes the reduction of uracil to 5, 6-dihydrouracil then dihydropyrimidinase hydrolyzes 5, 6-dihydrouracil to N-carbamyl-b-alanine. Finally, beta-ureidopropionase catalyzes the conversion of N-carbamyl-b-alanine to beta-alanine. 5,6-Dihydro-2,4(1H,3H)-pyrimidinedione 5,6-Dihydro-2,4-dihydroxypyrimidine 5,6-Dihydrouracil DI-H-uracil Dihydro-2,4(1H,3H)-pyrimidinedione Dihydro-pyrimidine-2,4-dione Dihydrouracil Dihydrouracile Hydrouracil C4H6N2O2 114.1026 114.042927446 1,3-diazinane-2,4-dione dihydrouracil 504-07-4 O=C1CCNC(=O)N1 InChI=1S/C4H6N2O2/c7-3-1-2-5-4(8)6-3/h1-2H2,(H2,5,6,7,8) OIVLITBTBDPEFK-UHFFFAOYSA-N Solid Cytosol logp -1.28 ALOGPS logs -0.64 ALOGPS solubility 2.59e+01 g/l ALOGPS melting_point 279-281 oC logp -1.2 ChemAxon pka_strongest_acidic 11.73 ChemAxon pka_strongest_basic -7.6 ChemAxon iupac 1,3-diazinane-2,4-dione ChemAxon average_mass 114.1026 ChemAxon mono_mass 114.042927446 ChemAxon smiles O=C1CCNC(=O)N1 ChemAxon formula C4H6N2O2 ChemAxon inchi InChI=1S/C4H6N2O2/c7-3-1-2-5-4(8)6-3/h1-2H2,(H2,5,6,7,8) ChemAxon inchikey OIVLITBTBDPEFK-UHFFFAOYSA-N ChemAxon polar_surface_area 58.2 ChemAxon refractivity 25.75 ChemAxon polarizability 10.13 ChemAxon rotatable_bond_count 0 ChemAxon acceptor_count 2 ChemAxon donor_count 2 ChemAxon physiological_charge 0 ChemAxon formal_charge 0 ChemAxon Pyrimidine metabolism The metabolism of pyrimidines begins with L-glutamine interacting with water molecule and a hydrogen carbonate through an ATP driven carbamoyl phosphate synthetase resulting in a hydrogen ion, an ADP, a phosphate, an L-glutamic acid and a carbamoyl phosphate. The latter compound interacts with an L-aspartic acid through a aspartate transcarbamylase resulting in a phosphate, a hydrogen ion and a N-carbamoyl-L-aspartate. The latter compound interacts with a hydrogen ion through a dihydroorotase resulting in the release of a water molecule and a 4,5-dihydroorotic acid. This compound interacts with an ubiquinone-1 through a dihydroorotate dehydrogenase, type 2 resulting in a release of an ubiquinol-1 and an orotic acid. The orotic acid then interacts with a phosphoribosyl pyrophosphate through a orotate phosphoribosyltransferase resulting in a pyrophosphate and an orotidylic acid. The latter compound then interacts with a hydrogen ion through an orotidine-5 '-phosphate decarboxylase, resulting in an release of carbon dioxide and an Uridine 5' monophosphate. The Uridine 5' monophosphate process to get phosphorylated by an ATP driven UMP kinase resulting in the release of an ADP and an Uridine 5--diphosphate. Uridine 5-diphosphate can be metabolized in multiple ways in order to produce a Deoxyuridine triphosphate. 1.-Uridine 5-diphosphate interacts with a reduced thioredoxin through a ribonucleoside diphosphate reductase 1 resulting in the release of a water molecule and an oxidized thioredoxin and an dUDP. The dUDP is then phosphorylated by an ATP through a nucleoside diphosphate kinase resulting in the release of an ADP and a DeoxyUridine triphosphate. 2.-Uridine 5-diphosphate interacts with a reduced NrdH glutaredoxin-like protein through a Ribonucleoside-diphosphate reductase 1 resulting in a release of a water molecule, an oxidized NrdH glutaredoxin-like protein and a dUDP. The dUDP is then phosphorylated by an ATP through a nucleoside diphosphate kinase resulting in the release of an ADP and a DeoxyUridine triphosphate. 3.-Uridine 5-diphosphate is phosphorylated by an ATP-driven nucleoside diphosphate kinase resulting in an ADP and an Uridinetriphosphate. The latter compound interacts with a reduced flavodoxin through ribonucleoside-triphosphate reductase resulting in the release of an oxidized flavodoxin, a water molecule and a Deoxyuridine triphosphate 4.-Uridine 5-diphosphate is phosphorylated by an ATP-driven nucleoside diphosphate kinase resulting in an ADP and an Uridinetriphosphate The uridine triphosphate interacts with a L-glutamine and a water molecule through an ATP driven CTP synthase resulting in an ADP, a phosphate, a hydrogen ion, an L-glutamic acid and a cytidine triphosphate. The cytidine triphosphate interacts with a reduced flavodoxin through a ribonucleoside-triphosphate reductase resulting in the release of a water molecule, an oxidized flavodoxin and a dCTP. The dCTP interacts with a water molecule and a hydrogen ion through a dCTP deaminase resulting in a release of an ammonium molecule and a Deoxyuridine triphosphate. 5.-Uridine 5-diphosphate is phosphorylated by an ATP-driven nucleoside diphosphate kinase resulting in an ADP and an Uridinetriphosphate The uridine triphosphate interacts with a L-glutamine and a water molecule through an ATP driven CTP synthase resulting in an ADP, a phosphate, a hydrogen ion, an L-glutamic acid and a cytidine triphosphate. The cytidine triphosphate then interacts spontaneously with a water molecule resulting in the release of a phosphate, a hydrogen ion and a CDP. The CDP then interacts with a reduced NrdH glutaredoxin-like protein through a ribonucleoside-diphosphate reductase 2 resulting in the release of a water molecule, an oxidized NrdH glutaredoxin-like protein and a dCDP. The dCDP is then phosphorylated through an ATP driven nucleoside diphosphate kinase resulting in an ADP and a dCTP. The dCTP interacts with a water molecule and a hydrogen ion through a dCTP deaminase resulting in a release of an ammonium molecule and a Deoxyuridine triphosphate. 6.-Uridine 5-diphosphate is phosphorylated by an ATP-driven nucleoside diphosphate kinase resulting in an ADP and an Uridinetriphosphate The uridine triphosphate interacts with a L-glutamine and a water molecule through an ATP driven CTP synthase resulting in an ADP, a phosphate, a hydrogen ion, an L-glutamic acid and a cytidine triphosphate. The cytidine triphosphate then interacts spontaneously with a water molecule resulting in the release of a phosphate, a hydrogen ion and a CDP. The CDP interacts with a reduced thioredoxin through a ribonucleoside diphosphate reductase 1 resulting in a release of a water molecule, an oxidized thioredoxin and a dCDP. The dCDP is then phosphorylated through an ATP driven nucleoside diphosphate kinase resulting in an ADP and a dCTP. The dCTP interacts with a water molecule and a hydrogen ion through a dCTP deaminase resulting in a release of an ammonium molecule and a Deoxyuridine triphosphate. The deoxyuridine triphosphate then interacts with a water molecule through a nucleoside triphosphate pyrophosphohydrolase resulting in a release of a hydrogen ion, a phosphate and a dUMP. The dUMP then interacts with a methenyltetrahydrofolate through a thymidylate synthase resulting in a dihydrofolic acid and a 5-thymidylic acid. Then 5-thymidylic acid is then phosphorylated through a nucleoside diphosphate kinase resulting in the release of an ADP and thymidine 5'-triphosphate. PW000942 ec00240 Metabolic Pantothenate and CoA biosynthesis The CoA biosynthesis requires compounds from two other pathways: aspartate metabolism and valine biosynthesis. It requires a Beta-Alanine and R-pantoate. The compound (R)-pantoate is generated in two reactions, as shown by the interaction of alpha-ketoisovaleric acid, 5,10 methylene-THF and water through a 3-methyl-2-oxobutanoate hydroxymethyltransferase resulting in a tetrahydrofolic acid and a 2-dehydropantoate. This compound interacts with hydrogen through a NADPH driven acetohydroxy acid isomeroreductase resulting in the release of NADP and R-pantoate. On the other hand L-aspartic acid interacts with a hydrogen ion and gets decarboxylated through an Aspartate 1- decarboxylase resulting in a carbon dioxide and a Beta-alanine. Beta-alanine and R-pantoate interact with an ATP driven pantothenate synthetase resulting in pyrophosphate, AMP, hydrogen ion and pantothenic acid. Pantothenic acid is phosphorylated through a ATP-driven pantothenate kinase resulting in a ADP, a hydrogen ion and D-4'-Phosphopantothenate. This compound interacts with a CTP and a L-cysteine resulting in a fused 4'-phosphopantothenoylcysteine decarboxylase and phosphopantothenoylcysteine synthetase resulting in a hydrogen ion, a pyrophosphate, a CMP and 4-phosphopantothenoylcysteine. The latter compound interacts with a hydrogen ion through a fused 4'-phosphopantothenoylcysteine decarboxylase and phosphopantothenoylcysteine synthetase resulting in a carbon dioxide release and a 4-phosphopantetheine. This compound interacts with an ATP, hydrogen ion and an phosphopantetheine adenylyltransferase resulting in a release of pyrophosphate, and dephospho-CoA. Dephospho-CoA reacts with an ATP driven dephospho-CoA kinase resulting in a ADP , a hydrogen ion and a Coenzyme A. . The latter is converted into (R)-4'-phosphopantothenate is two steps, involving a β-alanine ligase and a kinase. In most organsims the ligase acts before the kinase (EC 6.3.2.1, pantoate—β-alanine ligase (AMP-forming) followed by EC 2.7.1.33, pantothenate kinase, as described in phosphopantothenate biosynthesis I and phosphopantothenate biosynthesis II. However, in archaea the order is reversed, and EC 2.7.1.169, pantoate kinase acts before EC 6.3.2.36, 4-phosphopantoate—β-alanine ligase, as described in phosphopantothenate biosynthesis III. The kinases are feedback inhibited by CoA itself, accounting for the primary regulatory mechanism of CoA biosynthesis. The addition of L-cysteine to (R)-4'-phosphopantothenate, resulting in the formation of R-4'-phosphopantothenoyl-L-cysteine (PPC), is followed by decarboxylation of PPC to 4'-phosphopantetheine. The ultimate reaction is catalyzed by EC 2.7.1.24, dephospho-CoA kinase, which converts 4'-phosphopantetheine to CoA. All enzymes of this pathway are essential for growth. The reactions in the biosynthetic route towards CoA are identical in most organisms, although there are differences in the functionality of the involved enzymes. In plants every step is catalyzed by single monofunctional enzymes, whereas in bacteria and mammals bifunctional enzymes are often employed [Rubio06]. PW000828 ec00770 Metabolic Drug metabolism - other enzymes ec00983 beta-Alanine metabolism The Beta-Alanine Metabolism starts with a product of Aspartate metabolism. Aspartate is decarboxylated by aspartate 1-decarboxylase, releasing carbon dioxide and Beta-alanine. Beta alanine is then metabolized through a pantothenate synthetase resulting in Pantothenic acid undergoes phosphorylation through a ATP driven pantothenate kinase, resulting in D-4-phosphopantothenate. Pantothenate (vitamin B5) is the universal precursor for the synthesis of the 4'-phosphopantetheine moiety of coenzyme A and acyl carrier protein. Only plants and microorganismscan synthesize pantothenate de novo - animals require a dietary supplement. The enzymes of this pathway are therefore considered to be antimicrobial drug targets. PW000896 ec00410 Metabolic Metabolic pathways eco01100 Specdb::CMs 315 Specdb::CMs 1151 Specdb::CMs 1251 Specdb::CMs 25806 Specdb::CMs 30862 Specdb::CMs 30984 Specdb::CMs 30985 Specdb::CMs 31803 Specdb::CMs 31805 Specdb::CMs 173971 Specdb::EiMs 929 Specdb::NmrOneD 1071 Specdb::NmrOneD 2411 Specdb::NmrOneD 3101 Specdb::NmrOneD 5592 Specdb::NmrOneD 5593 Specdb::NmrOneD 5594 Specdb::NmrOneD 5595 Specdb::NmrOneD 5596 Specdb::NmrOneD 5597 Specdb::NmrOneD 5598 Specdb::NmrOneD 5599 Specdb::NmrOneD 5600 Specdb::NmrOneD 5601 Specdb::NmrOneD 5602 Specdb::NmrOneD 5603 Specdb::NmrOneD 5604 Specdb::NmrOneD 5605 Specdb::NmrOneD 5606 Specdb::NmrOneD 5607 Specdb::NmrOneD 5608 Specdb::NmrOneD 5609 Specdb::NmrOneD 5610 Specdb::NmrOneD 5611 Specdb::MsMs 123 Specdb::MsMs 124 Specdb::MsMs 125 Specdb::MsMs 2794 Specdb::MsMs 21041 Specdb::MsMs 21042 Specdb::MsMs 21043 Specdb::MsMs 22592 Specdb::MsMs 22593 Specdb::MsMs 22594 Specdb::MsMs 440047 Specdb::MsMs 448176 Specdb::MsMs 451880 Specdb::MsMs 2253489 Specdb::MsMs 2255092 Specdb::MsMs 2255472 Specdb::MsMs 2704826 Specdb::MsMs 2704827 Specdb::MsMs 2704828 Specdb::MsMs 3004146 Specdb::MsMs 3004147 Specdb::MsMs 3004148 Specdb::NmrTwoD 1129 HMDB00076 649 629 C00429 15901 DI-H-URACIL DUC Keseler, I. 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Organic Preparations and Procedures International (1983), 15(5), 303-13. http://hmdb.ca/system/metabolites/msds/000/000/055/original/HMDB00076.pdf?1358461785 D-phenylhydantoinase Q46806 PHYDA_ECOLI hyuA http://ecmdb.ca/proteins/Q46806.xml Uncharacterized protein yeiA P25889 YEIA_ECOLI yeiA http://ecmdb.ca/proteins/P25889.xml Uncharacterized oxidoreductase yeiT P76440 YEIT_ECOLI yeiT http://ecmdb.ca/proteins/P76440.xml Dihydrouracil + NAD <> Hydrogen ion + NADH + Uracil DIHYDROURACIL-DEHYDROGENASE-NAD+-RXN Dihydrouracil + Water <> Ureidopropionic acid R02269 Dihydrouracil + NAD > Uracil + NADH Dihydrouracil + NAD + Dihydrothymine <> Uracil + NADH + Hydrogen ion + Thymine R00977