If an enzyme name is shown in bold, there is experimental evidence for this enzymatic activity.
Locations of Mapped Genes:
|Superclasses:||Degradation/Utilization/Assimilation → Nucleosides and Nucleotides Degradation → Pyrimidine Nucleotides Degradation → Pyrimidine Nucleobases Degradation → Uracil Degradation|
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 [Kim10a].
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, Kim10a]. 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 3-oxopropanoate 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.
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
Kim10a: 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
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
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
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
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
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
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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