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Pathway: de novo biosynthesis of pyrimidine ribonucleotides

Biochemical pathways in S. cerevisiae are manually curated and maintained in the YeastPathways database. This page summarizes the genes, enzymes, and metabolites involved in the pathway, along with the curated literature.

Pathway Name
de novo biosynthesis of pyrimidine ribonucleotides
Pathway ID
PYRIMID-RNTSYN-PWY
SGD ID
SGD:S000249775
Genes
URA1 | URA10 | URA2 | URA3 | URA4 | URA5 | URA6 | URA7 | URA8 | YNK1
Aliases
pyrimsyn ; pyrimidine biosynthesis
Chemical Compounds
(S)-dihydroorotate | 5-O-phosphonato-alpha-D-ribofuranosyl diphosphate(5-) | ADP(3-) | ATP(4-) | CTP(4-) | L-aspartate(1-) | L-glutamate(1-) | L-glutamine zwitterion | N-carbamoyl-L-aspartate(2-) | UDP(3-) | UTP(4-) | ammonium | carbamate | carbamoyl phosphate(2-) | carbon dioxide | carboxyphosphate(2-) | diphosphoric acid | electron | hydrogencarbonate | hydrogenphosphate | hydron | orotate | orotidine 5'-phosphate(3-) | uridine 5'-monophosphate(2-) | water

Pathway Diagram

Diagram of the pathway from YeastPathways. Click "View interactive diagram at YeastPathways" for the zoomable, clickable version.

de novo biosynthesis of pyrimidine ribonucleotides pathway diagram

View interactive diagram at YeastPathways

Pathway Summary

Purine and pyrimidine nucleotides serve many diverse and essential roles in the cell. They are precursors to DNA, RNA, and many important metabolites (e.g. CDP-diacylglycerol). In addition, nucleotides can be used as an energy source (primarily as ATP), signaling molecules, and cofactor components (e.g. coenzyme A). In S. cerevisiae, the initial steps of de novo pyrimidine biosynthesis are catalyzed by the bifunctional carbamoylphosphate synthetaseaspartate transcarbamylase Ura2p. In the first step, Ura2p catalyzes the synthesis of carbamoylphosphate from CO2, ATP, and glutamine. In the second, Ura2p condenses carbamoylphosphate with aspartate to yield ureidosuccinatecarbamoyl-L-aspartate. Third, dihydroorotase (Ura4p) catalyzes closure of the pyrimidine ring of ureidosuccinate to form dihydroorotate (DHO). DHO, in turn, is oxidized to orotic acid (OA), condensed with phosphoribosyl pyrophosphate to form orotidine 5-monophosphate, and finally decarboxylated to yield UMP. These three steps are catalyzed by Ura1p, Ura5pUra10p, and Ura3p, respectively. UMP may then undergo further processing to form other pyrimidines. The de novo pyrimidine pathway is regulated at both the enzymatic and transcriptional levels. Ura2p, which catalyzes the first committed step of the pathway, is subject to end product feedback inhibition by UTP. Transcription of URA2 is repressed by UTP and uracil. Furthermore, transcription of URA2 and several other genes in the pathway is upregulated in response to pyrimidine starvation. Upregulation of URA1, URA3, and URA4 during pyrimidine starvation depends upon the zinc finger transcription factor Ppr1p. Two intermediates in the pyrimidine pathway regulate the transcriptional activity of Ppr1p: DHO and OA. At low concentrations, these intermediates convert Ppr1p into its active state, resulting in transcription of URA genes. High concentrations of DHO and OA, however, inhibit Ppr1p activity in vitro.

Genes Involved

Genes whose products participate in this pathway, with their systematic names, EC numbers (where the gene product is an enzyme with an assigned EC number), and the gene's SGD description.

GeneSystematic NameEC NumberDescription
URA1 YKL216W 1.3.98.1 Dihydroorotate dehydrogenase
URA10 YMR271C 2.4.2.10 Minor orotate phosphoribosyltransferase (OPRTase) isozyme
URA2 YJL130C 2.1.3.2, 3.5.1.2, 6.3.4.16, 6.3.5.5 Bifunctional carbamoylphosphate synthetase/aspartate transcarbamylase
URA3 YEL021W 4.1.1.23 Orotidine-5'-phosphate (OMP) decarboxylase
URA4 YLR420W 3.5.2.3 Dihydroorotase
URA5 YML106W 2.4.2.10 Major orotate phosphoribosyltransferase (OPRTase) isozyme
URA6 YKL024C 2.7.4.14 Uridylate kinase
URA7 YBL039C 6.3.4.2 Major CTP synthase isozyme (see also URA8)
URA8 YJR103W 6.3.4.2 Minor CTP synthase isozyme (see also URA7)
YNK1 YKL067W 2.7.4.6 Nucleoside diphosphate kinase

Functional Networks

Functional Networks show how the genes in this pathway work together: a graph linking the pathway to its genes and their shared GO biological-process terms and phenotype observables, and the GO-CAM causal activity models that involve these genes.

Shared Annotations

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GO-CAMs

GO-CAM (Gene Ontology Causal Activity Model) pathway models that involve the genes in this pathway. A gene can participate in more than one model, so use the dropdown to switch between them; the model for this pathway is shown by default.

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GO Enrichment

Gene Ontology biological-process terms enriched among the genes in this pathway, computed with GO Term Finder. Terms are shown with the number of pathway genes annotated to them and the corrected p-value.

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References

List of references used specifically to curate the information on this page.

Resources

YeastPathways