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A Second Pathway to Degrade Pyrimidine Nucleic Acid Precursors in Eukaryotes.

Andersen, Gorm LU ; Björnberg, Olof LU ; Poláková, Silvia LU ; Pynyaha, Yuriy; Rasmussen, Anna LU ; Møller, Kasper; Hofer, Anders; Moritz, Thomas; Sandrini, Michael LU and Merico, Anna-Maria, et al. (2008) In Journal of Molecular Biology 380(4). p.656-666
Abstract
Pyrimidine bases are the central precursors for RNA and DNA, and their intracellular pools are determined by de novo, salvage and catabolic pathways. In eukaryotes, degradation of uracil has been believed to proceed only via the reduction to dihydrouracil. Using a yeast model, Saccharomyces kluyveri, we show that during degradation, uracil is not reduced to dihydrouracil. Six loci, named URC1-6 (for uracil catabolism), are involved in the novel catabolic pathway. Four of them, URC3,5, URC6, and URC2 encode urea amidolyase, uracil phosphoribosyltransferase, and a putative transcription factor, respectively. The gene products of URC1 and URC4 are highly conserved proteins with so far unknown functions and they are present in a variety of... (More)
Pyrimidine bases are the central precursors for RNA and DNA, and their intracellular pools are determined by de novo, salvage and catabolic pathways. In eukaryotes, degradation of uracil has been believed to proceed only via the reduction to dihydrouracil. Using a yeast model, Saccharomyces kluyveri, we show that during degradation, uracil is not reduced to dihydrouracil. Six loci, named URC1-6 (for uracil catabolism), are involved in the novel catabolic pathway. Four of them, URC3,5, URC6, and URC2 encode urea amidolyase, uracil phosphoribosyltransferase, and a putative transcription factor, respectively. The gene products of URC1 and URC4 are highly conserved proteins with so far unknown functions and they are present in a variety of prokaryotes and fungi. In bacteria and in some fungi, URC1 and URC4 are linked on the genome together with the gene for uracil phosphoribosyltransferase (URC6). Urc1p and Urc4p are therefore likely the core components of this novel biochemical pathway. A combination of genetic and analytical chemistry methods demonstrates that uridine monophosphate and urea are intermediates, and 3-hydroxypropionic acid, ammonia and carbon dioxide the final products of degradation. The URC pathway does not require the presence of an active respiratory chain and is therefore different from the oxidative and rut pathways described in prokaryotes, although the latter also gives 3-hydroxypropionic acid as the end product. The genes of the URC pathway are not homologous to any of the eukaryotic or prokaryotic genes involved in pyrimidine degradation described to date. (Less)
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Contribution to journal
publication status
published
subject
keywords
urea, uracil degradation, nucleic acid precursors, metabolic pathways, 3-hydroxypropionic acid
in
Journal of Molecular Biology
volume
380
issue
4
pages
656 - 666
publisher
Elsevier
external identifiers
  • wos:000258046900007
  • scopus:45649084019
ISSN
1089-8638
DOI
10.1016/j.jmb.2008.05.029
language
English
LU publication?
yes
id
4c39b465-3ef9-4ad5-a24c-e58cca9dfc3e (old id 1168884)
date added to LUP
2008-11-27 13:11:35
date last changed
2017-01-01 06:17:39
@article{4c39b465-3ef9-4ad5-a24c-e58cca9dfc3e,
  abstract     = {Pyrimidine bases are the central precursors for RNA and DNA, and their intracellular pools are determined by de novo, salvage and catabolic pathways. In eukaryotes, degradation of uracil has been believed to proceed only via the reduction to dihydrouracil. Using a yeast model, Saccharomyces kluyveri, we show that during degradation, uracil is not reduced to dihydrouracil. Six loci, named URC1-6 (for uracil catabolism), are involved in the novel catabolic pathway. Four of them, URC3,5, URC6, and URC2 encode urea amidolyase, uracil phosphoribosyltransferase, and a putative transcription factor, respectively. The gene products of URC1 and URC4 are highly conserved proteins with so far unknown functions and they are present in a variety of prokaryotes and fungi. In bacteria and in some fungi, URC1 and URC4 are linked on the genome together with the gene for uracil phosphoribosyltransferase (URC6). Urc1p and Urc4p are therefore likely the core components of this novel biochemical pathway. A combination of genetic and analytical chemistry methods demonstrates that uridine monophosphate and urea are intermediates, and 3-hydroxypropionic acid, ammonia and carbon dioxide the final products of degradation. The URC pathway does not require the presence of an active respiratory chain and is therefore different from the oxidative and rut pathways described in prokaryotes, although the latter also gives 3-hydroxypropionic acid as the end product. The genes of the URC pathway are not homologous to any of the eukaryotic or prokaryotic genes involved in pyrimidine degradation described to date.},
  author       = {Andersen, Gorm and Björnberg, Olof and Poláková, Silvia and Pynyaha, Yuriy and Rasmussen, Anna and Møller, Kasper and Hofer, Anders and Moritz, Thomas and Sandrini, Michael and Merico, Anna-Maria and Compagno, Concetta and Åkerlund, Hans-Erik and Gojković, Zoran and Piskur, Jure},
  issn         = {1089-8638},
  keyword      = {urea,uracil degradation,nucleic acid
precursors,metabolic pathways,3-hydroxypropionic acid},
  language     = {eng},
  number       = {4},
  pages        = {656--666},
  publisher    = {Elsevier},
  series       = {Journal of Molecular Biology},
  title        = {A Second Pathway to Degrade Pyrimidine Nucleic Acid Precursors in Eukaryotes.},
  url          = {http://dx.doi.org/10.1016/j.jmb.2008.05.029},
  volume       = {380},
  year         = {2008},
}