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discounted EARLY registration ends Dec 31, 2014
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Metabolic Modeling Tutorial
discounted EARLY registration ends Dec 31, 2014
BioCyc websites down
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for maintenance.
Metabolic Modeling Tutorial
discounted EARLY registration ends Dec 31, 2014
BioCyc websites down
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for maintenance.
Metabolic Modeling Tutorial
discounted EARLY registration ends Dec 31, 2014
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Escherichia coli K-12 substr. MG1655 Pathway: uracil degradation III

If an enzyme name is shown in bold, there is experimental evidence for this enzymatic activity.

Locations of Mapped Genes:

Genetic Regulation Schematic: ?

Superclasses: Degradation/Utilization/Assimilation Nucleosides and Nucleotides Degradation Pyrimidine Nucleotides Degradation Pyrimidine Nucleobases Degradation Uracil Degradation

Summary:
General Background

Pyrimidines can be catabolized through three different pathways. The best characterized is the reductive pathway (thymine degradation and uracil degradation I (reductive)) in which pyrimidines are reduced to β-amino acids, CO2 and ammonia. The pathway is found in mammals, microorganisms and plants [Fritzson57, Campbell57, Traut96]. The oxidative pathway is only found in a few bacterial species and has not been characterized nearly as well. In it uracil is converted to urea and malonate via barbiturate [Hayaishi52, Lara52]. A third pathway has recently been discovered in E. coli [Loh06] and is described here.

About This Pathway

E. coli is able to utilize pyrimidine nucleosides and bases as the sole source of nitrogen at room temperature. This novel pathway for pyrimidine degradation was discovered by a combination of functional and comparative genomics techniques including high-throughput microarray and phenotype analysis [Loh06]. The pathway depicted here represents a combination of experimental work and functional predictions based on the available evidence [Kim10d].

In the presence of a flavin reductase, pyrimidine oxygenase catalyzes the first step in this pathway, the ring opening of uracil at the C4 carbonyl by a novel flavin hydroperoxide-catalyzed mechanism. The initial product of the reaction appears to be (Z)-3-ureidoacrylate peracid, which is unstable and can be slowly reduced to ureidoacrylate [Mukherjee10, Kim10d]. While the RutB enzyme is able to hydrolyze ureidoacrylate, it is thought to hydrolyze peroxyureidoacrylate in vivo, yielding carbamate and (Z)-3-peroxyaminoacrylate. In a spontaneous reaction, carbamate decomposes into one molecule each of ammonia and CO2. The aminoacrylate peracid is thought to be reduced to aminoacrylate by the predicted aminoacrylate peracid reductase. Aminoacrylate can then hydrolyze either spontaneously or enzymatically to malonate semialdehyde and a second molecule of ammonia. Malonate semialdehyde appears to be toxic and can not be utilized further. The compound may be detoxified by one of two malonic semialdehyde reductases to 3-hydroxypropanoate, which is then excreted into the medium. The toxicity of malonic semialdehyde appears to limit growth on pyrimidines as the sole source of nitrogen.

Reviews: [Osterman06, Piskur07, Parales10]

Credits:
Created 27-Apr-2010 by Keseler I , SRI International


References

Campbell57: Campbell LL (1957). "Reductive degradation of pyrimidines. I. The isolation and characterization of a uracil fermenting bacterium, Clostridium uracilicum nov. spec." J Bacteriol 73(2);220-4. PMID: 13416173

Fritzson57: Fritzson P (1957). "The catabolism of C14-labeled uracil, dihydrouracil, and beta-ureidopropionic acid in rat liver slices." J Biol Chem 226(1);223-8. PMID: 13428755

Hayaishi52: Hayaishi O, Kornberg A (1952). "Metabolism of cytosine, thymine, uracil, and barbituric acid by bacterial enzymes." J Biol Chem 197(2);717-32. PMID: 12981104

Kim10d: Kim KS, Pelton JG, Inwood WB, Andersen U, Kustu S, Wemmer DE (2010). "The Rut pathway for pyrimidine degradation: novel chemistry and toxicity problems." J Bacteriol 192(16):4089-102. PMID: 20400551

Lara52: Lara FJ (1952). "On the decomposition of pyrimidines by bacteria. II. Studies with cell-free enzyme preparations." J Bacteriol 64(2);279-85. PMID: 14955523

Loh06: Loh KD, Gyaneshwar P, Markenscoff Papadimitriou E, Fong R, Kim KS, Parales R, Zhou Z, Inwood W, Kustu S (2006). "A previously undescribed pathway for pyrimidine catabolism." Proc Natl Acad Sci U S A 103(13);5114-9. PMID: 16540542

Mukherjee10: Mukherjee T, Zhang Y, Abdelwahed S, Ealick SE, Begley TP (2010). "Catalysis of a Flavoenzyme-Mediated Amide Hydrolysis." J Am Chem Soc 132(16):5550-1. PMID: 20369853

Osterman06: Osterman A (2006). "A hidden metabolic pathway exposed." Proc Natl Acad Sci U S A 103(15);5637-8. PMID: 16595627

Parales10: Parales RE, Ingraham JL (2010). "The surprising Rut pathway: an unexpected way to derive nitrogen from pyrimidines." J Bacteriol 192(16);4086-8. PMID: 20562306

Piskur07: Piskur J, Schnackerz KD, Andersen G, Bjornberg O (2007). "Comparative genomics reveals novel biochemical pathways." Trends Genet 23(8);369-72. PMID: 17555842

Traut96: Traut TW, Jones ME (1996). "Uracil metabolism--UMP synthesis from orotic acid or uridine and conversion of uracil to beta-alanine: enzymes and cDNAs." Prog Nucleic Acid Res Mol Biol 53;1-78. PMID: 8650301

Other References Related to Enzymes, Genes, Subpathways, and Substrates of this Pathway

DiazMejia09: Diaz-Mejia JJ, Babu M, Emili A (2009). "Computational and experimental approaches to chart the Escherichia coli cell-envelope-associated proteome and interactome." FEMS Microbiol Rev 33(1);66-97. PMID: 19054114

Fujisawa03: Fujisawa H, Nagata S, Misono H (2003). "Characterization of short-chain dehydrogenase/reductase homologues of Escherichia coli (YdfG) and Saccharomyces cerevisiae (YMR226C)." Biochim Biophys Acta 1645(1);89-94. PMID: 12535615

GOA01: GOA, MGI (2001). "Gene Ontology annotation based on Enzyme Commission mapping." Genomics 74;121-128.

GOA01a: GOA, DDB, FB, MGI, ZFIN (2001). "Gene Ontology annotation through association of InterPro records with GO terms."

GOA06: GOA, SIB (2006). "Electronic Gene Ontology annotations created by transferring manual GO annotations between orthologous microbial proteins."

Ishihama08: Ishihama Y, Schmidt T, Rappsilber J, Mann M, Hartl FU, Kerner MJ, Frishman D (2008). "Protein abundance profiling of the Escherichia coli cytosol." BMC Genomics 9;102. PMID: 18304323

Khil02: Khil PP, Camerini-Otero RD (2002). "Over 1000 genes are involved in the DNA damage response of Escherichia coli." Mol Microbiol 44(1);89-105. PMID: 11967071

Knapik12: Knapik AA, Petkowski JJ, Otwinowski Z, Cymborowski MT, Cooper DR, Chruszcz M, Krajewska WM, Minor W (2012). "Structure of Escherichia coli RutC, a member of the YjgF family and putative aminoacrylate peracid reductase of the rut operon." Acta Crystallogr Sect F Struct Biol Cryst Commun 68(Pt 11);1294-9. PMID: 23143235

Lee05b: Lee LJ, Barrett JA, Poole RK (2005). "Genome-wide transcriptional response of chemostat-cultured Escherichia coli to zinc." J Bacteriol 187(3);1124-34. PMID: 15659689

Prosser10: Prosser GA, Copp JN, Syddall SP, Williams EM, Smaill JB, Wilson WR, Patterson AV, Ackerley DF (2010). "Discovery and evaluation of Escherichia coli nitroreductases that activate the anti-cancer prodrug CB1954." Biochem Pharmacol 79(5);678-87. PMID: 19852945

UniProtGOA11a: UniProt-GOA (2011). "Gene Ontology annotation based on manual assignment of UniProtKB keywords in UniProtKB/Swiss-Prot entries."

Zimmer00: Zimmer DP, Soupene E, Lee HL, Wendisch VF, Khodursky AB, Peter BJ, Bender RA, Kustu S (2000). "Nitrogen regulatory protein C-controlled genes of Escherichia coli: scavenging as a defense against nitrogen limitation." Proc Natl Acad Sci U S A 97(26);14674-9. PMID: 11121068


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Please cite the following article in publications resulting from the use of EcoCyc: Nucleic Acids Research 41:D605-12 2013
Page generated by SRI International Pathway Tools version 18.5 on Sat Dec 20, 2014, BIOCYC14B.