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discounted EARLY registration ends Dec 31, 2014
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discounted EARLY registration ends Dec 31, 2014
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MetaCyc Pathway: pyrimidine ribonucleosides degradation

Enzyme View:

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

Some taxa known to possess this pathway include ? : Escherichia coli K-12 substr. MG1655 , Homo sapiens

Expected Taxonomic Range: Archaea , Bacteria , Metazoa

Summary:
General Background

The predominant circulating pyrimidine in humans is uridine [Wu94, 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, Inoue95].

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

Credits:
Created 11-Dec-2006 by Ingraham JL , UC Davis


References

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

Cansev06: Cansev M (2006). "Uridine and cytidine in the brain: their transport and utilization." Brain Res Rev 52(2);389-97. PMID: 16769123

Connolly99: Connolly GP, Duley JA (1999). "Uridine and its nucleotides: biological actions, therapeutic potentials." Trends Pharmacol Sci 20(5);218-25. PMID: 10354618

Inoue95: Inoue S, Honda K, Komoda Y (1995). "Sleep as neuronal detoxification and restitution." Behav Brain Res 69(1-2);91-6. PMID: 7546322

Karle84: Karle JM, Anderson LW, Cysyk RL (1984). "Effect of plasma concentrations of uridine on pyrimidine biosynthesis in cultured L1210 cells." J Biol Chem 259(1);67-72. PMID: 6323418

Leer77: Leer JC, Hammer-Jespersen K, Schwartz M (1977). "Uridine phosphorylase from Escherichia coli. Physical and chemical characterization." Eur J Biochem 1977;75(1);217-24. PMID: 16751

Loffler05: Loffler M, Fairbanks LD, Zameitat E, Marinaki AM, Simmonds HA (2005). "Pyrimidine pathways in health and disease." Trends Mol Med 11(9);430-7. PMID: 16098809

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

Moyer85: Moyer JD, Henderson JF (1985). "Salvage of uridine in the mouse. Effect of uridine phosphorylase pretreatment." Biochem Pharmacol 34(1);101-5. PMID: 3966913

Reichard58: Reichard P, Skold O (1958). "Enzymes of uracil metabolism in the Ehrlich ascites tumour and mammalian liver." Biochim Biophys Acta 28(2);376-85. PMID: 13535735

Shambaugh79: Shambaugh GE (1979). "Pyrimidine biosynthesis." Am J Clin Nutr 32(6);1290-7. PMID: 35970

Traut94: Traut TW (1994). "Physiological concentrations of purines and pyrimidines." Mol Cell Biochem 140(1);1-22. PMID: 7877593

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

Wu94: 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

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

Ashley82: Ashley GW, Bartlett PA (1982). "A phosphorus-containing pyrimidine analog as a potent inhibitor of cytidine deaminase." Biochem Biophys Res Commun 108(4);1467-74. PMID: 6758781

Ashley84: Ashley GW, Bartlett PA (1984). "Purification and properties of cytidine deaminase from escherichia coli." J Biol Chem 1984;259(21);13615-20. PMID: 6386817

Ashley84a: Ashley GW, Bartlett PA (1984). "Inhibition of Escherichia coli cytidine deaminase by a phosphapyrimidine nucleoside." J Biol Chem 259(21);13621-7. PMID: 6386818

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

BRENDA14: BRENDA team (2014). "Imported from BRENDA version existing on Aug 2014." http://www.brenda-enzymes.org.

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

Carlow98: Carlow D, Wolfenden R (1998). "Substrate connectivity effects in the transition state for cytidine deaminase." Biochemistry 37(34);11873-8. PMID: 9718310

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

Carter95: Carter CW (1995). "The nucleoside deaminases for cytidine and adenosine: structure, transition state stabilization, mechanism, and evolution." Biochimie 77(1-2);92-8. PMID: 7599282

Chung05: Chung SJ, Fromme JC, Verdine GL (2005). "Structure of human cytidine deaminase bound to a potent inhibitor." J Med Chem 48(3);658-60. PMID: 15689149

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

Cohen71a: Cohen RM, Wolfenden R (1971). "The equilibrium of hydrolytic deamination of cytidine and N 4 -methylcytidine." J Biol Chem 246(24);7566-8. PMID: 4944312

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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Report Errors or Provide Feedback
Please cite the following article in publications resulting from the use of MetaCyc: Caspi et al, Nucleic Acids Research 42:D459-D471 2014
Page generated by SRI International Pathway Tools version 18.5 on Fri Nov 28, 2014, BIOCYC14A.