This view shows enzymes only for those organisms listed below, in the list of taxa known to possess the pathway. If an enzyme name is shown in bold, there is experimental evidence for this enzymatic activity.
|Superclasses:||Degradation/Utilization/Assimilation → Nucleosides and Nucleotides Degradation → Pyrimidine Nucleotides Degradation → Pyrimidine Ribonucleosides Degradation|
The predominant circulating pyrimidine in humans is uridine [Wu94a, Cansev06]. Among different species, including man, its plasma level is strictly maintained at 3-5 μM, a concentration higher than that of other nucleosides [Traut94]. Uridine, produced de novo in the liver and kedney, is circulated to other organs, where it serves as an important precursor of pyrimidine salvage pathways [Shambaugh79, Karle84, Moyer85, Traut96, Barsotti02].
Cells maintain uridine concentration by balancing its input, its salvage, and its catabolism.The main enzyme responsible for uridine catabolism is uridine phosphorylase.
About This Pathway
Uridine phosphorylase breaks down uridine to the free base uracil and to α-D-ribose-1-phosphate. Uracil is catabolized to β-alanine in a process considered to be restricted to the liver (see uracil degradation I (reductive)) [Reichard58, Connolly99, Loffler05], while α-D-ribose-1-phosphate is converted into 5-phospho-α-D-ribose 1-diphosphate (PRPP), which is used in the salvage synthesis of purine nucleotides [Wice82, Inoue95a].
Since the phosphorylase is not capable of cleaving cytidine, this nucleoside must be deaminated to uridine before it can be used by the cell.
While the overall metabolic outcome of this pathway, the conversion of cytidine to uracil, is identical to that achieved by salvage pathways, as described in pyrimidine ribonucleosides salvage II and pyrimidine ribonucleosides salvage III, this pathway is known to function as a catabolic pathway.
Catabolic nucleoside degradation is also found in bacteria. The bacterium Escherichia coli can use both naturally occurring pyrimidine ribonucleosides (cytidine and uridine) as total sources of carbon and energy. The amino nitrogen of cytidine (but not the ring-nitrogen of uracil) can serve as a total nitrogen source for Escherichia coli over its entire temperature range of growth. At room temperature, the ring nitrogen becomes available as a total nitrogen source via a uracil degradation pathway encoded by genes in the rut operon [Loh06]. α-D-ribose-1-phosphate, after being converted to D-ribose 5-phosphate by phosphopentomutase, enters central metabolism through the nonoxidative branch of the pentose phosphate pathway.
Plants and yeast do not have uridine phosphorylase, and thus can not utilize this pathway.
Superpathways: superpathway of pyrimidine ribonucleosides degradation
Unification Links: EcoCyc:PWY0-1295
Barsotti02: Barsotti C, Tozzi MG, Ipata PL (2002). "Purine and pyrimidine salvage in whole rat brain. Utilization of ATP-derived ribose-1-phosphate and 5-phosphoribosyl-1-pyrophosphate generated in experiments with dialyzed cell-free extracts." J Biol Chem 277(12);9865-9. PMID: 11782482
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 T.W., Jones M.E. "Uracil metabolism - UMP synthesis from orotic acid or uridine and conversion of uracil to β-alanine: enzymes and cDNAs." Prog. Nucleic Acid Res Mol. Biol. (1996) 53 : 1-78. PMID: 8650301
Wice82: Wice BM, Kennell D (1982). "Ribose-1-P is the essential precursor for nucleic acid synthesis in animal cells growing on uridine in the absence of sugar." J Biol Chem 257(5);2578-83. PMID: 6277907
Wu94a: Wu X, Gutierrez MM, Giacomini KM (1994). "Further characterization of the sodium-dependent nucleoside transporter (N3) in choroid plexus from rabbit." Biochim Biophys Acta 1191(1);190-6. PMID: 8155674
Betts89: Betts L, Frick L, Wolfenden R, Carter CW (1989). "Incomplete factorial search for conditions leading to high quality crystals of Escherichia coli cytidine deaminase complexed to a transition state analog inhibitor." J Biol Chem 1989;264(12);6737-40. PMID: 2651432
Betts94: Betts L, Xiang S, Short SA, Wolfenden R, Carter CW (1994). "Cytidine deaminase. The 2.3 A crystal structure of an enzyme: transition-state analog complex." J Mol Biol 235(2);635-56. PMID: 8289286
Borchers04: Borchers CH, Marquez VE, Schroeder GK, Short SA, Snider MJ, Speir JP, Wolfenden R (2004). "Fourier transform ion cyclotron resonance MS reveals the presence of a water molecule in an enzyme transition-state analogue complex." Proc Natl Acad Sci U S A 101(43);15341-5. PMID: 15494437
Budman67: Budman DR, Pardee AB (1967). "Thymidine and thymine incorporation into deoxyribonucleic acid: inhibition and repression by uridine of thymidine phosphorylase of Escherichia coli." J Bacteriol 94(5);1546-50. PMID: 4862197
Burling03: Burling FT, Kniewel R, Buglino JA, Chadha T, Beckwith A, Lima CD (2003). "Structure of Escherichia coli uridine phosphorylase at 2.0 A." Acta Crystallogr D Biol Crystallogr 59(Pt 1);73-6. PMID: 12499542
CaradocDavies04: Caradoc-Davies TT, Cutfield SM, Lamont IL, Cutfield JF (2004). "Crystal structures of Escherichia coli uridine phosphorylase in two native and three complexed forms reveal basis of substrate specificity, induced conformational changes and influence of potassium." J Mol Biol 337(2);337-54. PMID: 15003451
Carlow95: Carlow DC, Smith AA, Yang CC, Short SA, Wolfenden R (1995). "Major contribution of a carboxymethyl group to transition-state stabilization by cytidine deaminase: mutation and rescue." Biochemistry 1995;34(13);4220-4. PMID: 7703234
Carlow96: Carlow DC, Short SA, Wolfenden R (1996). "Role of glutamate-104 in generating a transition state analogue inhibitor at the active site of cytidine deaminase." Biochemistry 35(3);948-54. PMID: 8547277
Carlow98a: Carlow DC, Short SA, Wolfenden R (1998). "Complementary truncations of a hydrogen bond to ribose involved in transition-state stabilization by cytidine deaminase." Biochemistry 37(5);1199-203. PMID: 9477944
Carlow99: Carlow DC, Carter CW, Mejlhede N, Neuhard J, Wolfenden R (1999). "Cytidine deaminases from B. subtilis and E. coli: compensating effects of changing zinc coordination and quaternary structure." Biochemistry 38(38);12258-65. PMID: 10493793
Cohen71: Cohen RM, Wolfenden R (1971). "Cytidine deaminase from Escherichia coli. Purification, properties and inhibition by the potential transition state analog 3,4,5,6-tetrahydrouridine." J Biol Chem 246(24);7561-5. PMID: 4944311
Demontis98: Demontis S, Terao M, Brivio M, Zanotta S, Bruschi M, Garattini E (1998). "Isolation and characterization of the gene coding for human cytidine deaminase." Biochim Biophys Acta 1443(3);323-33. PMID: 9878810
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