2.0 2012-05-31 10:26:02 -0600 2015-09-13 12:56:07 -0600 ECMDB00300 M2MDB000126 Uracil Uracil is a common naturally occurring pyrimidine found in RNA, it base pairs with adenine and is replaced by thymine in DNA. Methylation of uracil produces thymine. Uracil serves as allosteric regulator and coenzyme for many important biochemical reactions. Uracil is also involved in the biosynthesis of polysaccharides and the transportation of sugars containing aldehydes. In E. coli, uracil catabolism is regulated by the amount of metabolically available nitrogen. (PMID: 4567228) 2,4-Dihydroxypyrimidine 2,4-Dioxopyrimidine 2,4-Pyrimidinediol 2,4-Pyrimidinedione Hybar X Pirod Pyrod Uracil C4H4N2O2 112.0868 112.027277382 1,2,3,4-tetrahydropyrimidine-2,4-dione uracil 66-22-8 O=C1NC=CC(=O)N1 InChI=1S/C4H4N2O2/c7-3-1-2-5-4(8)6-3/h1-2H,(H2,5,6,7,8) ISAKRJDGNUQOIC-UHFFFAOYSA-N Solid Cytosol Extra-organism Periplasm logp -1.20 ALOGPS logs -0.63 ALOGPS solubility 2.65e+01 g/l ALOGPS melting_point 330 oC logp -0.86 ChemAxon pka_strongest_acidic 8.8 ChemAxon pka_strongest_basic -5.5 ChemAxon iupac 1,2,3,4-tetrahydropyrimidine-2,4-dione ChemAxon average_mass 112.0868 ChemAxon mono_mass 112.027277382 ChemAxon smiles O=C1NC=CC(=O)N1 ChemAxon formula C4H4N2O2 ChemAxon inchi InChI=1S/C4H4N2O2/c7-3-1-2-5-4(8)6-3/h1-2H,(H2,5,6,7,8) ChemAxon inchikey ISAKRJDGNUQOIC-UHFFFAOYSA-N ChemAxon polar_surface_area 58.2 ChemAxon refractivity 25.97 ChemAxon polarizability 9.37 ChemAxon rotatable_bond_count 0 ChemAxon acceptor_count 2 ChemAxon donor_count 2 ChemAxon physiological_charge 0 ChemAxon formal_charge 0 ChemAxon Arginine and proline metabolism ec00330 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 Purine degradation Pseudouridine is phosphorylated by interacting with atp and a psuK resulting in the release of an ADP, a hydrogen ion and a pseudouridine 5'-phosphate. The latter compound then reacts with water through a pseudouridine 5'-phosphate glycosidase resulting in the release of a uracil and D-ribofuranose 5-phosphate PW001887 Metabolic Pyrimidine ribonucleosides degradtion Cytidine and Uridine are transported through their corresponding nucleoside hydrogen symporters . Once cytidine is incorporated into the cytosol, it is deaminated through a reaction with water and a hydrogen ion through a cytidine deaminase resulting in the release of ammonium and uridine. Uridine is then lyase by a phosphate through a uridine phosphorylase resulting in the release of a uracil and a alpha-D-ribose-1-phosphate. This compound is then transformed into an isomer D-ribose 5-phosphate through a alpha-D-ribose 1,5-phosphomutase. This cumpound is then incorporated into the pentose phosphate pathway PW002024 Metabolic Uracil degradation III PW002026 Metabolic pyrimidine deoxyribonucleosides degradation The degradation of deoxycytidine starts with deoxycytidine being introduced into the cytosol through either a nupG or nupC symporter. Once inside, it can can be degrade through water,a hydrogen ion and a deoxycytidien deaminsa resultin in the release of a ammonium and a a deoxyuridine. The deoxyuridine is then degraded through a uracil phosphorylase resulting in the release of a deoxyribose 1-phosphate and a uracil. The degradation of thymidine starts with thymidine being introduced into the cytosol through either a nupG or nupC symporter. Thymidine is then degrades through a phosphorylase resulting in the release of a thymine and a deoxyribose 1-phosphate. PW002063 Metabolic salvage pathways of pyrimidine deoxyribonucleotides The pathway begins with the introduction of deoxycytidine into the cytosol, either through a nupG symporter or a nupC symporter. Once inside it is deaminated when reacting with a water molecule, a hydrogen ion and a deoxycytidine deaminase resulting in the release of an ammonium and a deoxyuridine. Deoxyuridine can also be imported through a nupG symporter or a nupC symporter. Deoxyuridine can react with an ATP through a deoxyuridine kinase resulting in the release of a ADP , a hydrogen ion and a dUMP. Deoxyuridine can also react with a phosphate through a uracil phosphorylase resulting in the release of a uracil and a deoxy-alpha-D-ribose 1-phosphate. This compound in turn reacts with a thymine through a thymidine phosphorylase resulting in the release of a phosphate and a thymidine. Thymidine in turn reacts with an ATP through a thymidine kinase resulting in a release of an ADP, a hydrogen ion and a dTMP PW002061 Metabolic pyrimidine ribonucleosides degradation The degradation of pyrimidine ribonucleosides starts with either cytidine or uridine being transported into the cytosol. Cytidine is transported into the cytosol through an nupG transporter. Once inside the cytosol, it can be degraded into uridine by reacting with water and ahydrogen ion through a cytidine deaminase resulting in the release of ammonium and uridine. Uridine is transported into the cytosol through a nupG. Once in the cytosol , uridine can be degrade by reacting with phosphate through a uridine phosphorylase resulting in the release of an alpha-D-ribose-1-phosphate and a uracil. The alpha-D-ribose-1-phosphate reacts with an alpha-d-ribose 1,5-phosphomutase resulting in the release of a D-ribose 5-phosphate which can be incorporated into the pentose phosphate pathway. PW002104 Metabolic salvage pathways of pyrimidine deoxyribonucleotides PWY0-181 pyrimidine deoxyribonucleosides degradation PWY0-1298 uracil degradation III PWY0-1471 salvage pathways of pyrimidine ribonucleotides PWY0-163 pyrimidine ribonucleosides degradation I PWY0-1295 Specdb::CMs 529 Specdb::CMs 530 Specdb::CMs 1056 Specdb::CMs 3073 Specdb::CMs 29052 Specdb::CMs 29557 Specdb::CMs 30706 Specdb::CMs 30824 Specdb::CMs 31120 Specdb::CMs 31804 Specdb::CMs 168787 Specdb::EiMs 430 Specdb::NmrOneD 1229 Specdb::NmrOneD 1321 Specdb::NmrOneD 2568 Specdb::NmrOneD 3264 Specdb::NmrOneD 4763 Specdb::NmrOneD 143410 Specdb::NmrOneD 143411 Specdb::NmrOneD 143412 Specdb::NmrOneD 143413 Specdb::NmrOneD 143414 Specdb::NmrOneD 143415 Specdb::NmrOneD 143416 Specdb::NmrOneD 143417 Specdb::NmrOneD 143418 Specdb::NmrOneD 143419 Specdb::NmrOneD 143420 Specdb::NmrOneD 143421 Specdb::NmrOneD 143422 Specdb::NmrOneD 143423 Specdb::NmrOneD 143424 Specdb::NmrOneD 143425 Specdb::NmrOneD 143426 Specdb::NmrOneD 143427 Specdb::NmrOneD 143428 Specdb::NmrOneD 143429 Specdb::MsMs 510 Specdb::MsMs 511 Specdb::MsMs 512 Specdb::MsMs 3964 Specdb::MsMs 3965 Specdb::MsMs 3966 Specdb::MsMs 3967 Specdb::MsMs 3968 Specdb::MsMs 3969 Specdb::MsMs 3970 Specdb::MsMs 3973 Specdb::MsMs 3974 Specdb::MsMs 20012 Specdb::MsMs 20013 Specdb::MsMs 20014 Specdb::MsMs 21563 Specdb::MsMs 21564 Specdb::MsMs 21565 Specdb::MsMs 438568 Specdb::MsMs 438569 Specdb::MsMs 438570 Specdb::MsMs 438571 Specdb::MsMs 438572 Specdb::MsMs 439025 Specdb::MsMs 440041 Specdb::NmrTwoD 1017 Specdb::NmrTwoD 1263 HMDB00300 1174 1141 C00106 17568 URACIL URA Uracil 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 Vijayendran, C., Barsch, A., Friehs, K., Niehaus, K., Becker, A., Flaschel, E. (2008). "Perceiving molecular evolution processes in Escherichia coli by comprehensive metabolite and gene expression profiling." Genome Biol 9:R72. 18402659 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 Ban, J., Vitale, L., Kos, E. (1972). "Thymine and uracil catabolism in Escherichia coli." J Gen Microbiol 73:267-272. 4567228 Sreekumar A, Poisson LM, Rajendiran TM, Khan AP, Cao Q, Yu J, Laxman B, Mehra R, Lonigro RJ, Li Y, Nyati MK, Ahsan A, Kalyana-Sundaram S, Han B, Cao X, Byun J, Omenn GS, Ghosh D, Pennathur S, Alexander DC, Berger A, Shuster JR, Wei JT, Varambally S, Beecher C, Chinnaiyan AM: Metabolomic profiles delineate potential role for sarcosine in prostate cancer progression. Nature. 2009 Feb 12;457(7231):910-4. 19212411 Hofmann U, Schwab M, Seefried S, Marx C, Zanger UM, Eichelbaum M, Murdter TE: Sensitive method for the quantification of urinary pyrimidine metabolites in healthy adults by gas chromatography-tandem mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci. 2003 Jul 5;791(1-2):371-80. 12798197 van Lenthe H, van Kuilenburg AB, Ito T, Bootsma AH, van Cruchten A, Wada Y, van Gennip AH: Defects in pyrimidine degradation identified by HPLC-electrospray tandem mass spectrometry of urine specimens or urine-soaked filter paper strips. Clin Chem. 2000 Dec;46(12):1916-22. 11106323 Jiang H, Jiang J, Hu P, Hu Y: Measurement of endogenous uracil and dihydrouracil in plasma and urine of normal subjects by liquid chromatography-tandem mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci. 2002 Mar 25;769(1):169-76. 11936689 Sweatman BC, Farrant RD, Holmes E, Ghauri FY, Nicholson JK, Lindon JC: 600 MHz 1H-NMR spectroscopy of human cerebrospinal fluid: effects of sample manipulation and assignment of resonances. J Pharm Biomed Anal. 1993 Aug;11(8):651-64. 8257730 Allgayer H, Kolb M, Stuber V, Kruis W: Effects of bile acids on base hydroxylation in a model of human colonic mucosal DNA. Cancer Detect Prev. 2002;26(1):85-9. 12088208 Jakobs C, Sweetman L, Nyhan WL, Gruenke L, Craig JC, Wadman SK: Stable isotope dilution analysis of orotic acid and uracil in amniotic fluid. Clin Chim Acta. 1984 Nov 15;143(2):123-33. 6391739 van Kuilenburg AB, van Lenthe H, Loffler M, van Gennip AH: Analysis of pyrimidine synthesis &quot;de novo&quot; intermediates in urine and dried urine filter- paper strips with HPLC-electrospray tandem mass spectrometry. Clin Chem. 2004 Nov;50(11):2117-24. Epub 2004 Sep 16. 15375016 Spector T, Harrington JA, Porter DJ: 5-Ethynyluracil (776C85): inactivation of dihydropyrimidine dehydrogenase in vivo. Biochem Pharmacol. 1993 Dec 14;46(12):2243-8. 8274158 Mani S, Kugler JW, Sciortino DF, Garcia JC, Ansari RH, Humerickhouse R, Michelassi F, Posner MC, Shulman KL, Schilsky RL, List M, Vokes EE, Benner S: Phase II trial of uracil/tegafur (UFT) plus leucovorin in patients with advanced pancreatic carcinoma: a University of Chicago phase II consortium study. Ann Oncol. 1998 Sep;9(9):1035-7. 9818081 Tomita T, Tajima T, Ishibashi M, Tagaya N, Aoki H, Itoh S, Kadowaki A, Kogure H, Tajima Y: [Study on the concentrations of 5-fluorouracil (5-FU), tegafur (ET) and uracil in bile: comparison of UFT or FT] Gan To Kagaku Ryoho. 1989 Dec;16(12):3755-62. 2512859 Duthie SJ, McMillan P: Uracil misincorporation in human DNA detected using single cell gel electrophoresis. Carcinogenesis. 1997 Sep;18(9):1709-14. 9328165 Bayer AS, Galpin JE, Theofilopoulos AN, Guze LB: Neurological disease associated with Mycoplasma pneumoniae pneumonitis: demonstration of viable Mycoplasma pneumoniae in cerebrospinal fluid and blood by radioisotopic and immunofluorescent tissue culture techniques. Ann Intern Med. 1981 Jan;94(1):15-20. 6778283 Feliu J, Mel R, Borrega P, Lopez Gomez L, Escudero P, Dorta J, Castro J, Vazquez-Estevez SE, Bolanos M, Espinosa E, Gonzalez Baron M: Phase II study of a fixed dose-rate infusion of gemcitabine associated with uracil/tegafur in advanced carcinoma of the pancreas. Ann Oncol. 2002 Nov;13(11):1756-62. 12419748 Mashiyama ST, Courtemanche C, Elson-Schwab I, Crott J, Lee BL, Ong CN, Fenech M, Ames BN: Uracil in DNA, determined by an improved assay, is increased when deoxynucleosides are added to folate-deficient cultured human lymphocytes. Anal Biochem. 2004 Jul 1;330(1):58-69. 15183762 DeAngelis LM, Kreis W, Chan K, Dantis E, Akerman S: Pharmacokinetics of ara-C and ara-U in plasma and CSF after high-dose administration of cytosine arabinoside. Cancer Chemother Pharmacol. 1992;29(3):173-7. 1733548 Stover PJ, Garza C: Bringing individuality to public health recommendations. J Nutr. 2002 Aug;132(8 Suppl):2476S-2480S. 12163715 Duthie SJ, Hawdon A: DNA instability (strand breakage, uracil misincorporation, and defective repair) is increased by folic acid depletion in human lymphocytes in vitro. FASEB J. 1998 Nov;12(14):1491-7. 9806758 Hanaue H, Kurosawa T, Kitano Y, Miyakawa S, Nemoto A, Yamamoto H, Asagoe T, Takada T, Yasuda H, Shikata J: Anticancer drug distribution in lymph and blood during adjuvant chemotherapy after surgery for gastric carcinoma. A study with a combined preparation of 1-(2-tetrahydrofuryl)-5-fluorouracil and uracil. Cancer. 1987 May 1;59(9):1571-6. 3103905 Burckhalter, J. H.; Scarborough, Homer C. The synthesis of uracils as anticonvulsants. Journal of the American Pharmaceutical Association (1912-1977) (1955), 44 545-50. http://hmdb.ca/system/metabolites/msds/000/000/219/original/HMDB00300.pdf?1358896161 Thymidine phosphorylase P07650 TYPH_ECOLI deoA http://ecmdb.ca/proteins/P07650.xml Uracil phosphoribosyltransferase P0A8F0 UPP_ECOLI upp http://ecmdb.ca/proteins/P0A8F0.xml Purine nucleoside phosphorylase deoD-type P0ABP8 DEOD_ECOLI deoD http://ecmdb.ca/proteins/P0ABP8.xml Uridine phosphorylase P12758 UDP_ECOLI udp http://ecmdb.ca/proteins/P12758.xml Non-specific ribonucleoside hydrolase rihC P22564 RIHC_ECOLI rihC http://ecmdb.ca/proteins/P22564.xml Cytosine deaminase P25524 CODA_ECOLI codA http://ecmdb.ca/proteins/P25524.xml Pyrimidine-specific ribonucleoside hydrolase rihB P33022 RIHB_ECOLI rihB http://ecmdb.ca/proteins/P33022.xml Pyrimidine-specific ribonucleoside hydrolase rihA P41409 RIHA_ECOLI rihA http://ecmdb.ca/proteins/P41409.xml Putative flavin reductase rutF P75893 RUTF_ECOLI rutF http://ecmdb.ca/proteins/P75893.xml Uncharacterized protein yeiA P25889 YEIA_ECOLI yeiA http://ecmdb.ca/proteins/P25889.xml Putative monooxygenase rutA P75898 RUTA_ECOLI rutA http://ecmdb.ca/proteins/P75898.xml Uncharacterized oxidoreductase yeiT P76440 YEIT_ECOLI yeiT http://ecmdb.ca/proteins/P76440.xml Uracil permease P0AGM7 URAA_ECOLI uraA http://ecmdb.ca/proteins/P0AGM7.xml Putative pyrimidine permease rutG P75892 RUTG_ECOLI rutG http://ecmdb.ca/proteins/P75892.xml Outer membrane protein N P77747 OMPN_ECOLI ompN http://ecmdb.ca/proteins/P77747.xml Outer membrane pore protein E P02932 PHOE_ECOLI phoE http://ecmdb.ca/proteins/P02932.xml Outer membrane protein F P02931 OMPF_ECOLI ompF http://ecmdb.ca/proteins/P02931.xml Outer membrane protein C P06996 OMPC_ECOLI ompC http://ecmdb.ca/proteins/P06996.xml Hydrogen ion + NADH + Oxygen + Uracil > NAD + Ureidoacrylate peracid Dihydrouracil + NAD <> Hydrogen ion + NADH + Uracil DIHYDROURACIL-DEHYDROGENASE-NAD+-RXN Water + Uridine > Ribose + Uracil Deoxyuridine + Phosphate <> Deoxyribose 1-phosphate + Uracil R02484 Cytosine + Hydrogen ion + Water > Ammonium + Uracil Phosphoribosyl pyrophosphate + Uracil <> Pyrophosphate + Uridine 5'-monophosphate R00966 URACIL-PRIBOSYLTRANS-RXN Phosphate + Uridine <> Ribose-1-phosphate + Uracil URPHOS-RXN Uridine 5'-monophosphate + Pyrophosphate <> Uracil + Phosphoribosyl pyrophosphate R00966 Cytosine + Water <> Uracil + Ammonia R00974 CYTDEAM-RXN Uridine + Phosphate <> Uracil + alpha-D-Ribose 1-phosphate + Ribose-1-phosphate R01876 Uracil + FMNH + Oxygen <> Ureidoacrylate peracid + Flavin Mononucleotide R09936 RXN0-6444 Deoxyuridine + Phosphate <> deoxyribose-1-phosphate + Uracil URA-PHOSPH-RXN Water + Cytosine > Ammonia + Uracil CYTDEAM-RXN D-Ribose-5-phosphate + Uracil <> Water + Pseudouridine 5'-phosphate RXN0-5398 Uracil + Oxygen + FMNH > Hydrogen ion + Ureidoacrylate peracid + Flavin Mononucleotide RXN0-6444 Pyrophosphate + Uridine 5'-monophosphate < Phosphoribosyl pyrophosphate + Uracil URACIL-PRIBOSYLTRANS-RXN Uridine + Water > D-ribose + Uracil URIDINE-NUCLEOSIDASE-RXN Dihydrouracil + NAD > Uracil + NADH Pseudouridine 5'-phosphate + Water > Uracil + D-Ribose-5-phosphate RXN0-5398 Uracil + FMNH(2) + Oxygen > Ureidoacrylate peracid + Flavin Mononucleotide + Water Uridine + Inorganic phosphate > Uracil + Ribose-1-phosphate Uridine 5'-monophosphate + Pyrophosphate > Uracil + Phosphoribosyl pyrophosphate Dihydrouracil + NAD + Dihydrothymine <> Uracil + NADH + Hydrogen ion + Thymine R00977 Uracil + FMNH + Oxygen + Thymine <> Ureidoacrylate peracid + Flavin Mononucleotide + (Z)-2-Methyl-ureidoacrylate peracid R09936 Pseudouridine 5'-phosphate + Water > Uracil + D-ribofuranose 5-phosphate + D-ribofuranose 5-phosphate PW_R005151 Uracil + FMNH2 + Oxygen > Ureidoacrylate peracid + Flavin Mononucleotide + Hydrogen ion + Peroxyaminoacrylate PW_R005905 Uridine + Phosphate > Uracil + Ribose-1-phosphate PW_R005898 Deoxyuridine + Phosphate > Uracil + Deoxyribose 1-phosphate PW_R006018 Cytosine + Water <> Uracil + Ammonia Phosphoribosyl pyrophosphate + Uracil <> Pyrophosphate + Uridine 5'-monophosphate Cytosine + Water <> Uracil + Ammonia Phosphoribosyl pyrophosphate + Uracil <> Pyrophosphate + Uridine 5'-monophosphate Luria-Bertani (LB) media Shake flask 1013.0 uM true 99.0 37 oC BL21 DE3 Stationary phase cultures (overnight culture) 4052000 396000 Lin, Z., Johnson, L. C., Weissbach, H., Brot, N., Lively, M. O., Lowther, W. T. (2007). "Free methionine-(R)-sulfoxide reductase from Escherichia coli reveals a new GAF domain function." Proc Natl Acad Sci U S A 104:9597-9602. 17535911