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MetaCyc Pathway: pyrimidine ribonucleosides salvage II
Inferred from experiment

Enzyme View:

Pathway diagram: pyrimidine ribonucleosides salvage II

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: BiosynthesisNucleosides and Nucleotides BiosynthesisPyrimidine Nucleotide BiosynthesisPyrimidine Nucleotides Salvage
Degradation/Utilization/AssimilationNucleosides and Nucleotides DegradationPyrimidine Nucleotides DegradationPyrimidine Ribonucleosides Degradation

Some taxa known to possess this pathway include : Arabidopsis thaliana col, Escherichia coli K-12 substr. MG1655, Saccharomyces cerevisiae

Expected Taxonomic Range: Archaea, Bacteria , Fungi, Viridiplantae

General Background

The essential ribonucleoside triphosphates ( UTP and CTP) can be synthesized either de novo (see superpathway of pyrimidine ribonucleotides de novo biosynthesis) or by utilizing free pyrimidine bases ( uracil and cytosine) or their nucleosides ( uridine and cytidine) by importing them from the environment. Both free bases and nucleosides can be imported into the cell by specialized transporters [Griffith96, Mourad12, Choi12]. On the other hand, nucleotides (which are phosphorylated) can not be imported due to their negative charge, and thus can not be salvaged from the environment.

Salvage is very important for many types of organisms and cells. Studies with the plant Arabidopsis thaliana showed that uracil salvage is necessary for early development [Mainguet09] and that uridine salvage plays a crucial role in photoassimilate allocation and partioning [Chen11b]. The inability to salvage uracil caused a light-dependent dramatic pale-green to albino phenotype, dwarfism and the inability to produce viable progeny in loss-of-function mutants [Mainguet09]. In mammals it is generally accepted that only the liver and kidney maintain de novo pyrimidine and purine synthesis, and supply other tissues and organs, including the brain, with pyrimidine nucleosides (mainly uridine) and purine nucleosides and bases for nucleotide synthesis [Barsotti02, Cao05, Cansev06].

Any of the pyrimidine bases and pyrimidine nucleosides can in theory serve as a total source of pyrimidine for ribonucleoside triphosphates biosynthesis (and subsequently for deoxyribonucleoside triphosphates synthesis). It is well documented that yeast prefer to salvage nucleobases, while animals prefer the salvage of nucleosides.

About This Pathway

In this pathway, the pyrimidine nucleoside cytidine is first deaminated by cytidine deaminase to uridine [Vincenzetti99, FaivreNitschke99], which is hydrolyzed by ribonucleoside hydrolase to free the pyrimidine base uracil by removal of the sugar ribose group [Jung09].

The resulting uracil base can be salvaged to form a pyrimidine nucleotide (see pyrimidine nucleobases salvage I and pyrimidine ribonucleosides salvage I). Alternatively, uracil can be degraded to β-alanine by releasing NH3 and CO2 in a three step reductive pathway ( uracil degradation I (reductive)). β-Alanine is a precursor of pentothenate and coenzyme A.

The overall metabolic outcome of this pathway, the conversion of cytidine to uracil, can also be achieved by a different pathway, as described in pyrimidine ribonucleosides salvage III.

Mammals do not have the enzyme ribonucleoside hydrolase and thus can not salvage uridine by this pathway. Instead they utilize a nucleoside kinase-based pathway (see pyrimidine nucleobases salvage I).

Citations: [Zrenner06 ]

Superpathways: superpathway of pyrimidine ribonucleosides salvage

Unification Links: EcoCyc:PWY-6556

Created 23-Jul-2010 by Zhang P, TAIR


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

Cao05: Cao D, Leffert JJ, McCabe J, Kim B, Pizzorno G (2005). "Abnormalities in uridine homeostatic regulation and pyrimidine nucleotide metabolism as a consequence of the deletion of the uridine phosphorylase gene." J Biol Chem 280(22);21169-75. PMID: 15772079

Chen11b: Chen M, Thelen JJ (2011). "Plastid uridine salvage activity is required for photoassimilate allocation and partitioning in Arabidopsis." Plant Cell 23(8);2991-3006. PMID: 21828290

Choi12: Choi JS, Berdis AJ (2012). "Nucleoside transporters: biological insights and therapeutic applications." Future Med Chem 4(11);1461-78. PMID: 22857534

FaivreNitschke99: Faivre-Nitschke SE, Grienenberger JM, Gualberto JM (1999). "A prokaryotic-type cytidine deaminase from Arabidopsis thaliana gene expression and functional characterization." Eur J Biochem 263(3);896-903. PMID: 10469156

Griffith96: Griffith DA, Jarvis SM (1996). "Nucleoside and nucleobase transport systems of mammalian cells." Biochim Biophys Acta 1286(3);153-81. PMID: 8982282

Jung09: Jung B, Florchinger M, Kunz HH, Traub M, Wartenberg R, Jeblick W, Neuhaus HE, Mohlmann T (2009). "Uridine-ribohydrolase is a key regulator in the uridine degradation pathway of Arabidopsis." Plant Cell 21(3);876-91. PMID: 19293370

Mainguet09: Mainguet SE, Gakiere B, Majira A, Pelletier S, Bringel F, Guerard F, Caboche M, Berthome R, Renou JP (2009). "Uracil salvage is necessary for early Arabidopsis development." Plant J 60(2);280-91. PMID: 19563437

Mourad12: Mourad GS, Tippmann-Crosby J, Hunt KA, Gicheru Y, Bade K, Mansfield TA, Schultes NP (2012). "Genetic and molecular characterization reveals a unique nucleobase cation symporter 1 in Arabidopsis." FEBS Lett 586(9);1370-8. PMID: 22616996

Vincenzetti99: Vincenzetti S, Cambi A, Neuhard J, Schnorr K, Grelloni M, Vita A (1999). "Cloning, expression, and purification of cytidine deaminase from Arabidopsis thaliana." Protein Expr Purif 15(1);8-15. PMID: 10024464

Zrenner06: Zrenner R, Stitt M, Sonnewald U, Boldt R (2006). "Pyrimidine and purine biosynthesis and degradation in plants." Annu Rev Plant Biol 57;805-36. PMID: 16669783

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

Belenky07: Belenky P, Racette FG, Bogan KL, McClure JM, Smith JS, Brenner C (2007). "Nicotinamide riboside promotes Sir2 silencing and extends lifespan via Nrk and Urh1/Pnp1/Meu1 pathways to NAD+." Cell 129(3);473-84. PMID: 17482543

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

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

Dance01: Dance GS, Beemiller P, Yang Y, Mater DV, Mian IS, Smith HC (2001). "Identification of the yeast cytidine deaminase CDD1 as an orphan C-->U RNA editase." Nucleic Acids Res 29(8);1772-80. PMID: 11292850

DeLisa01: DeLisa MP, Wu CF, Wang L, Valdes JJ, Bentley WE (2001). "DNA microarray-based identification of genes controlled by autoinducer 2-stimulated quorum sensing in Escherichia coli." J Bacteriol 183(18);5239-47. PMID: 11514505

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

Evans75: Evans BE, Mitchell GN, Wolfenden R (1975). "The action of bacterial cytidine deaminase on 5,6-dihydrocytidine." Biochemistry 14(3);621-4. PMID: 1090298

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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
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