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Pathway: de novo biosynthesis of purine nucleotides

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 purine nucleotides
Pathway ID
DENOVOPURINE3-PWY
SGD ID
SGD:S000249774
Genes
ADE1 | ADE12 | ADE13 | ADE16 | ADE17 | ADE2 | ADE4 | ADE57 | ADE6 | ADE8 | ADK1 | ADK2 | GUA1 | GUK1 | IMD2 | IMD3 | IMD4 | RNR1 | RNR2 | RNR3 | RNR4 | TRX1 | TRX2 | TRX3 | YNK1
Aliases
pursyn ; purine biosynthesis
Chemical Compounds
2-formamido-N(1)-(5-phospho-D-ribosyl)acetamidine | 5'-xanthylate(2-) | 5-O-phosphonato-alpha-D-ribofuranosyl diphosphate(5-) | 5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide(2-) | 5-amino-1-(5-phosphonato-D-ribosyl)imidazole-4-carboxylate | 5-amino-1-(5-phosphonato-beta-D-ribosyl)imidazol-3-ium | 5-formamido-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide(2-) | 5-phospho-beta-D-ribosylaminium(1-) | ADP(3-) | ATP(4-) | GDP(3-) | GTP(4-) | IMP(2-) | L-aspartate(1-) | L-glutamate(1-) | L-glutamine zwitterion | N(1)-(5-phospho-D-ribosyl)glycinamide(1-) | N(2)-formyl-N(1)-(5-phospho-D-ribosyl)glycinamide(2-) | N(6)-(1,2-dicarboxylatoethyl)-AMP(4-) | NAD(1-) | NADH(2-) | SAICAR(4-) | adenosine 5'-monophosphate(2-) | ammonium | carbon dioxide | dADP(3-) | dATP(4-) | dGDP(3-) | dGTP(4-) | diphosphoric acid | formate | fumarate(2-) | glycine zwitterion | guanosine 5'-monophosphate(2-) | hydrogenphosphate | hydron | water

Pathway Diagram

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

de novo biosynthesis of purine nucleotides 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). De novo purine nucleotide biosynthesis in yeast involves the 10-step production of the purine nucleotide inosine monophosphate (IMP), the common precursor to both adenosine monophosphate (AMP) and guanosine monophosphate (GMP). Synthesis of IMP begins with a reaction catalyzed by amidophosphoribosyltransferase (Ade4p) between PRPP (5-phosphoribosylpyrophosphate), glutamine, and water. Glutamine displaces the pyrophosphate group of PRPP, converting PRPP to phosphoribosylamine. The amino group of phosphoribosylamine subsequently reacts with a carboxyl group of glycine via Ade5,7p, forming the amide bond of phosphoribosylglycinamide. In the third reaction of the pathway, a tetrahydrofolate cofactor donates a one-carbon unit at the oxidation level of formate to the -amino group of phosphoribosylglycinamide. This forms phosphoribosyl-N-formylglycinamide, which reacts with an amino group from glutamine via Ade6p to form phosphoribosylformylglycinamidine. In three ATP-dependent steps, this product then undergoes closure of the imidazole ring by Ade5,7p, carboxylation by Ade2p, and condensation with aspartate by Ade1p. Adenylosuccinate lyase (Ade13p) subsequently catalyzes cleavage with release of fumarate to form aminoimidazole carboxamide ribonucleotide (AICAR). In the final two steps, Ade16p or Ade17p introduce a formyl group to the amino group on the imidazole ring, then condense the formyl carbon with the nitrogen from the amide group. This results in closure of the 6-membered ring and yields the purine nucleotide IMP. The incorporation of an aspartate group to IMP, followed by cleavage with the loss of fumarate, results in the conversion IMP to AMP. These reactions are catalyzed by adenylosuccinate synthetase (Ade12p) and adenylosuccinate lyase (Ade13p), respectively. Oxidation of IMP, on the other hand, converts it to xanthosine monophosphate (XMP). XMP can be amidated (using glutamine as the donor) to form GMP in a reaction catalyzed by GMP synthase (Gua1p).

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
ADE1 YAR015W 6.3.2.6 N-succinyl-5-aminoimidazole-4-carboxamide ribotide synthetase
ADE12 YNL220W 6.3.4.4 Adenylosuccinate synthase
ADE13 YLR359W 4.3.2.2 Adenylosuccinate lyase
ADE16 YLR028C 2.1.2.3, 3.5.4.10 Enzyme of 'de novo' purine biosynthesis
ADE17 YMR120C 2.1.2.3, 3.5.4.10 Enzyme of 'de novo' purine biosynthesis
ADE2 YOR128C 4.1.1.21 Phosphoribosylaminoimidazole carboxylase
ADE4 YMR300C 2.4.2.14 Phosphoribosylpyrophosphate amidotransferase (PRPPAT)
ADE57 YGL234W 6.3.3.1, 6.3.4.13 Bifunctional enzyme of 'de novo' purine nucleotide pathway
ADE6 YGR061C 6.3.5.3 Formylglycinamidine-ribonucleotide (FGAM)-synthetase
ADE8 YDR408C 2.1.2.2 Phosphoribosyl-glycinamide transformylase
ADK1 YDR226W 2.7.4.3 Adenylate kinase, required for purine metabolism
ADK2 YER170W 2.7.4.10 Mitochondrial adenylate kinase
GUA1 YMR217W 6.3.5.2 GMP synthase
GUK1 YDR454C 2.7.4.8 Guanylate kinase
IMD2 YHR216W 1.1.1.205 Inosine monophosphate dehydrogenase
IMD3 YLR432W 1.1.1.205 Inosine monophosphate dehydrogenase
IMD4 YML056C 1.1.1.205 Inosine monophosphate dehydrogenase
RNR1 YER070W 1.17.4.1 Major isoform of large subunit of ribonucleotide-diphosphate reductase
RNR2 YJL026W 1.17.4.1 Ribonucleotide-diphosphate reductase (RNR), small subunit
RNR3 YIL066C 1.17.4.1 Minor isoform of large subunit of ribonucleotide-diphosphate reductase
RNR4 YGR180C 1.17.4.1 Ribonucleotide-diphosphate reductase (RNR) small subunit
TRX1 YLR043C Cytoplasmic thioredoxin isoenzyme
TRX2 YGR209C Cytoplasmic thioredoxin isoenzyme
TRX3 YCR083W Mitochondrial thioredoxin
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