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:||Biosynthesis → Nucleosides and Nucleotides Biosynthesis → Pyrimidine Nucleotide Biosynthesis → Pyrimidine Nucleotides Salvage|
|Degradation/Utilization/Assimilation → Nucleosides and Nucleotides Degradation → Pyrimidine Nucleotides Degradation → Pyrimidine Ribonucleosides Degradation|
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.
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
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
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
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
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
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
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
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
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