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Pathway Description
Pyrimidine Metabolism
Escherichia coli
Category:
Metabolite Pathway
Sub-Category:
Metabolic
Created: 2015-06-11
Last Updated: 2019-08-13
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.
References
Pyrimidine Metabolism References
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Okada K, Ohara K, Yazaki K, Nozaki K, Uchida N, Kawamukai M, Nojiri H, Yamane H: The AtPPT1 gene encoding 4-hydroxybenzoate polyprenyl diphosphate transferase in ubiquinone biosynthesis is required for embryo development in Arabidopsis thaliana. Plant Mol Biol. 2004 Jul;55(4):567-77. doi: 10.1007/s11103-004-1298-4.
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Zhou L, Lacroute F, Thornburg R: Cloning, expression in Escherichia coli, and characterization of Arabidopsis thaliana UMP/CMP kinase. Plant Physiol. 1998 May;117(1):245-54.
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Schroder M, Giermann N, Zrenner R: Functional analysis of the pyrimidine de novo synthesis pathway in solanaceous species. Plant Physiol. 2005 Aug;138(4):1926-38. doi: 10.1104/pp.105.063693. Epub 2005 Jul 15.
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Piette J, Nyunoya H, Lusty CJ, Cunin R, Weyens G, Crabeel M, Charlier D, Glansdorff N, Pierard A: DNA sequence of the carA gene and the control region of carAB: tandem promoters, respectively controlled by arginine and the pyrimidines, regulate the synthesis of carbamoyl-phosphate synthetase in Escherichia coli K-12. Proc Natl Acad Sci U S A. 1984 Jul;81(13):4134-8. doi: 10.1073/pnas.81.13.4134.
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Turnbough CL Jr, Hicks KL, Donahue JP: Attenuation control of pyrBI operon expression in Escherichia coli K-12. Proc Natl Acad Sci U S A. 1983 Jan;80(2):368-72. doi: 10.1073/pnas.80.2.368.
Pubmed: 6300835
Cunin R, Jacobs A, Charlier D, Crabeel M, Herve G, Glansdorff N, Pierard A: Structure-function relationship in allosteric aspartate carbamoyltransferase from Escherichia coli. I. Primary structure of a pyrI gene encoding a modified regulatory subunit. J Mol Biol. 1985 Dec 20;186(4):707-13. doi: 10.1016/0022-2836(85)90390-0.
Pubmed: 3912513
Schachman HK, Pauza CD, Navre M, Karels MJ, Wu L, Yang YR: Location of amino acid alterations in mutants of aspartate transcarbamoylase: Structural aspects of interallelic complementation. Proc Natl Acad Sci U S A. 1984 Jan;81(1):115-9. doi: 10.1073/pnas.81.1.115.
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Pubmed: 2885307
Washabaugh MW, Collins KD: Dihydroorotase from Escherichia coli. Purification and characterization. J Biol Chem. 1984 Mar 10;259(5):3293-8.
Pubmed: 6142052
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Pubmed: 15826651
Poulsen P, Jensen KF, Valentin-Hansen P, Carlsson P, Lundberg LG: Nucleotide sequence of the Escherichia coli pyrE gene and of the DNA in front of the protein-coding region. Eur J Biochem. 1983 Sep 15;135(2):223-9. doi: 10.1111/j.1432-1033.1983.tb07641.x.
Pubmed: 6349999
Poulsen P, Bonekamp F, Jensen KF: Structure of the Escherichia coli pyrE operon and control of pyrE expression by a UTP modulated intercistronic attentuation. EMBO J. 1984 Aug;3(8):1783-90.
Pubmed: 6207018
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Turnbough CL Jr, Kerr KH, Funderburg WR, Donahue JP, Powell FE: Nucleotide sequence and characterization of the pyrF operon of Escherichia coli K12. J Biol Chem. 1987 Jul 25;262(21):10239-45.
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Aiba H, Baba T, Hayashi K, Inada T, Isono K, Itoh T, Kasai H, Kashimoto K, Kimura S, Kitakawa M, Kitagawa M, Makino K, Miki T, Mizobuchi K, Mori H, Mori T, Motomura K, Nakade S, Nakamura Y, Nashimoto H, Nishio Y, Oshima T, Saito N, Sampei G, Horiuchi T, et al.: A 570-kb DNA sequence of the Escherichia coli K-12 genome corresponding to the 28.0-40.1 min region on the linkage map. DNA Res. 1996 Dec 31;3(6):363-77. doi: 10.1093/dnares/3.6.363.
Pubmed: 9097039
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Yamanaka K, Ogura T, Niki H, Hiraga S: Identification and characterization of the smbA gene, a suppressor of the mukB null mutant of Escherichia coli. J Bacteriol. 1992 Dec;174(23):7517-26. doi: 10.1128/jb.174.23.7517-7526.1992.
Pubmed: 1447125
Serina L, Blondin C, Krin E, Sismeiro O, Danchin A, Sakamoto H, Gilles AM, Barzu O: Escherichia coli UMP-kinase, a member of the aspartokinase family, is a hexamer regulated by guanine nucleotides and UTP. Biochemistry. 1995 Apr 18;34(15):5066-74. doi: 10.1021/bi00015a018.
Pubmed: 7711027
Fujita N, Mori H, Yura T, Ishihama A: Systematic sequencing of the Escherichia coli genome: analysis of the 2.4-4.1 min (110,917-193,643 bp) region. Nucleic Acids Res. 1994 May 11;22(9):1637-9. doi: 10.1093/nar/22.9.1637.
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Hama H, Almaula N, Lerner CG, Inouye S, Inouye M: Nucleoside diphosphate kinase from Escherichia coli; its overproduction and sequence comparison with eukaryotic enzymes. Gene. 1991 Aug 30;105(1):31-6. doi: 10.1016/0378-1119(91)90510-i.
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Almaula N, Lu Q, Delgado J, Belkin S, Inouye M: Nucleoside diphosphate kinase from Escherichia coli. J Bacteriol. 1995 May;177(9):2524-9. doi: 10.1128/jb.177.9.2524-2529.1995.
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Yamamoto Y, Aiba H, Baba T, Hayashi K, Inada T, Isono K, Itoh T, Kimura S, Kitagawa M, Makino K, Miki T, Mitsuhashi N, Mizobuchi K, Mori H, Nakade S, Nakamura Y, Nashimoto H, Oshima T, Oyama S, Saito N, Sampei G, Satoh Y, Sivasundaram S, Tagami H, Horiuchi T, et al.: Construction of a contiguous 874-kb sequence of the Escherichia coli -K12 genome corresponding to 50.0-68.8 min on the linkage map and analysis of its sequence features. DNA Res. 1997 Apr 28;4(2):91-113. doi: 10.1093/dnares/4.2.91.
Pubmed: 9205837
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