GO:0006220 pyrimidine nucleotide metabolic process: Biosynthesis Pathway, Genes, Functions and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:0006220 pyrimidine nucleotide metabolic process describes the chemical reactions and pathways involving pyrimidine nucleotides, which are nucleosides (pyrimidine base linked to ribose or deoxyribose) esterified with a phosphate group at the 3' or 5' hydroxyl of the sugar.
• Pyrimidine nucleotides (UMP, CMP, dTMP and their di- and triphosphates) are essential for RNA and DNA synthesis, phospholipid and glycogen metabolism, and glycosylation reactions.
• The de novo pathway builds the pyrimidine ring on a ribose scaffold, while salvage pathways recycle preformed bases; both are tightly regulated to match cellular demand.
• Dysregulation of pyrimidine nucleotide metabolism is linked to cancer, mitochondrial DNA-dependent innate immunity, and antiviral drug targeting.
• Model organisms such as zebrafish and Pseudomonas species have provided insights into conserved pyrimidine biosynthetic regulation.
• CRISPR-based knockout, point mutation, knock-in, and overexpression models enable causal dissection of pyrimidine metabolic genes in human cells and animal models.
Description
Pyrimidine nucleotide metabolic process (GO:0006220) encompasses the chemical reactions and pathways involving pyrimidine nucleotides, which are compounds consisting of a nucleoside (a pyrimidine base linked to a deoxyribose or ribose sugar) esterified with a phosphate group at either the 3' or 5'-hydroxyl group of the sugar. These nucleotides are fundamental building blocks for RNA and DNA, and they also participate in activated intermediate forms used in phospholipid, glycogen, and glycosaminoglycan synthesis. The balance between de novo synthesis and salvage pathways is critical for maintaining nucleotide pools, and its disruption can trigger mitochondrial DNA-dependent innate immune responses. Research into pyrimidine nucleotide metabolism spans microbiology, cancer biology, virology, and developmental genetics. In Pseudomonas species, the control of pyrimidine nucleotide formation has been studied to understand bacterial physiology and potential antimicrobial targets. In humans, the de novo pyrimidine biosynthesis pathway is a validated target for antiviral chemotherapy, as many viruses depend on host nucleotide pools for replication. Zebrafish models have emerged as powerful systems to study disorders of pyrimidine nucleotide metabolism due to their optical transparency and genetic tractability. Dysregulation of de novo nucleotide biosynthetic pathway enzymes is a hallmark of many cancers, offering opportunities for targeted therapeutic intervention. Understanding the genes, enzymes, and regulatory mechanisms of pyrimidine nucleotide metabolism is therefore essential for both basic and translational research. This article provides a comprehensive overview of GO:0006220, including its definition, core biological processes, key genes, disease associations, and modern research methods including CRISPR-based models.
pyrimidine nucleotide metabolic process At A Glance
| GO ID | GO:0006220 |
|---|---|
| GO term | pyrimidine nucleotide metabolic process |
| Ontology | biological_process |
| Synonym | pyrimidine metabolic process; pyrimidine metabolism; pyrimidine nucleotide metabolism |
| Major function | Synthesis, interconversion, and degradation of pyrimidine nucleotides (UMP, CMP, dTMP, and their di-/triphosphates) for nucleic acid synthesis and cellular metabolism |
| Key pathways | De novo biosynthesis (CAD, DHODH, UMPS, CTPS), salvage (UK, TK1, HPRT), and catabolism |
| Cellular location | Cytosol, mitochondria, and nucleus depending on the specific enzyme and pathway |
| Regulation | Allosteric feedback by end products (UTP, CTP), transcriptional control, and post-translational modifications |
| Disease relevance | Cancer, mitochondrial DNA-dependent innate immunity, antiviral targeting, and inborn errors of metabolism |
What Is GO:0006220?
GO:0006220 pyrimidine nucleotide metabolic process is defined as the chemical reactions and pathways involving a pyrimidine nucleotide, a compound consisting of a nucleoside (a pyrimidine base linked to a deoxyribose or ribose sugar) esterified with a phosphate group at either the 3' or 5'-hydroxyl group of the sugar. In simpler terms, it covers all the enzymatic steps that build, interconvert, and break down pyrimidine nucleotides such as UMP, CMP, dTMP, and their phosphorylated derivatives. This process includes both de novo synthesis from small molecules (e.g., bicarbonate, glutamine, aspartate) and salvage pathways that recycle preformed pyrimidine bases.
Why Is pyrimidine nucleotide metabolic process Important in Cell Biology?
Pyrimidine nucleotide metabolism is essential for all living cells because it provides the activated precursors for RNA and DNA synthesis, as well as key intermediates for phospholipid and glycogen metabolism. Imbalances in pyrimidine nucleotide pools can cause replication stress, mitochondrial dysfunction, and activation of innate immune responses. In cancer, upregulated de novo pyrimidine biosynthesis supports rapid proliferation, making enzymes like DHODH and CAD attractive therapeutic targets. In virology, many viruses rely on host pyrimidine nucleotide pools, and inhibitors of these pathways are used as antiviral agents. Furthermore, inherited disorders of pyrimidine metabolism can cause severe neurological and hematological phenotypes, and model organisms such as zebrafish are helping to uncover these mechanisms.
• Provides the essential building blocks (UMP, CMP, dTMP) for RNA and DNA synthesis in all cells.
• Supplies activated nucleotide sugars for glycosylation and phospholipid synthesis.
• Maintains mitochondrial DNA replication and integrity; imbalance triggers innate immunity.
• Dysregulated in many cancers, where de novo pathway enzymes are often overexpressed.
• Targeted by antiviral drugs that exploit viral dependence on host nucleotide pools.
• Studied in model organisms like zebrafish to understand developmental and metabolic disorders.
• Bacterial pyrimidine metabolism is a potential target for new antibiotics.
• Inborn errors in pyrimidine salvage enzymes cause rare genetic diseases.
• Serves as a paradigm for feedback regulation and metabolic channeling.
• CRISPR screens can identify synthetic lethal interactions with pyrimidine pathway inhibitors.
What Happens During pyrimidine nucleotide metabolic process?
De Novo Pyrimidine Biosynthesis
In simple terms: The cell builds the pyrimidine ring from scratch on a ribose scaffold.
De novo pyrimidine biosynthesis begins with the formation of carbamoyl phosphate from bicarbonate, glutamine, and ATP by carbamoyl phosphate synthetase II (CAD in humans). This is followed by condensation with aspartate to form carbamoyl aspartate, cyclization to dihydroorotate, oxidation to orotate by DHODH, and attachment to ribose-5-phosphate to form orotidine monophosphate (OMP). OMP is decarboxylated by UMPS to uridine monophosphate (UMP), the central pyrimidine nucleotide. UMP is then phosphorylated to UDP and UTP, and CTP is formed by CTP synthase (CTPS). Deoxyribonucleotides are generated by ribonucleotide reductase (RRM1/RRM2) and thymidylate synthase (TYMS).
Salvage Pathways
In simple terms: The cell recycles preformed pyrimidine bases and nucleosides to save energy.
Salvage pathways recover pyrimidines from nucleic acid turnover or extracellular sources. Uridine kinase (UCK1/2) phosphorylates uridine and cytidine to UMP and CMP, respectively. Thymidine kinase 1 (TK1) phosphorylates thymidine to dTMP. Deoxycytidine kinase (DCK) phosphorylates deoxycytidine and other deoxynucleosides. These pathways are particularly important in tissues with high nucleotide demand, such as proliferating lymphocytes and cancer cells.
Interconversion and Catabolism
In simple terms: Nucleotides can be converted into each other or broken down for excretion.
Pyrimidine nucleotides undergo interconversion: UMP can be phosphorylated to UTP and aminated to CTP; dUMP is methylated to dTMP by TYMS. Catabolism of pyrimidines involves dephosphorylation by nucleotidases, deamination (e.g., cytidine deaminase, CDA), and cleavage by dihydropyrimidine dehydrogenase (DPYD), dihydropyrimidinase (DPYS), and beta-ureidopropionase (UPB1) to yield beta-alanine or beta-aminoisobutyrate, which enter further metabolism. Defects in catabolic enzymes can cause severe toxicity to chemotherapeutic drugs like 5-fluorouracil.
Compartmentalization and Channeling
In simple terms: Different steps happen in different parts of the cell and are physically linked.
In eukaryotes, de novo pyrimidine biosynthesis is spatially organized: CAD and DHODH are associated with mitochondria and the cytosol, while subsequent steps occur in the cytosol. DHODH is located on the outer face of the inner mitochondrial membrane and is coupled to the respiratory chain via ubiquinone, linking pyrimidine synthesis to mitochondrial energy metabolism. This compartmentalization allows efficient channeling of intermediates and coordination with mitochondrial function. Disruption of this organization can lead to pyrimidine imbalance and mitochondrial DNA release, triggering innate immunity.
Regulation of Pyrimidine Nucleotide Pools
In simple terms: The cell constantly adjusts production to match demand via feedback and gene expression.
Pyrimidine nucleotide biosynthesis is regulated at multiple levels. CAD is activated by PRPS1/2 and inhibited by UTP; DHODH is inhibited by orotate and regulated by ubiquinone availability; CTPS is allosterically activated by GTP and inhibited by CTP. Transcriptional regulation via the mTOR pathway and cell cycle-dependent expression of enzymes like TK1 and RRM2 ensures that nucleotide production peaks during S phase. In bacteria such as Pseudomonas, pyrimidine formation is controlled by pyrimidine-responsive regulators and feedback inhibition.
Key Genes Involved in GO:0006220 pyrimidine nucleotide metabolic process
The following genes encode key enzymes and regulators of pyrimidine nucleotide metabolic process (GO:0006220) in humans and model organisms.
| Gene | Major Role | Research Relevance |
|---|---|---|
| CAD | Trifunctional enzyme (carbamoyl phosphate synthetase II, aspartate transcarbamoylase, dihydroorotase) initiating de novo pyrimidine biosynthesis | Target in cancer and antiviral research; mutations affect enzyme activity |
| DHODH | Dihydroorotate dehydrogenase, catalyzes the fourth step in de novo synthesis; linked to mitochondrial respiratory chain | Inhibitors used in cancer, autoimmune diseases, and antiviral therapy; key for mitochondrial function |
| UMPS | Uridine monophosphate synthase (orotate phosphoribosyltransferase and OMP decarboxylase) | Deficiency causes orotic aciduria; target for chemotherapy |
| CTPS1/2 | CTP synthase, converts UTP to CTP | Essential for CTP supply; mutations cause immunodeficiency; target in cancer |
| RRM1/RRM2 | Ribonucleotide reductase subunits, convert NDPs to dNDPs | Targets for cancer therapy; regulated by cell cycle and DNA damage |
| TYMS | Thymidylate synthase, converts dUMP to dTMP | Target of 5-fluorouracil and other antifolates; predictive biomarker in cancer |
| TK1 | Thymidine kinase 1, salvage of thymidine to dTMP | Proliferation marker; target for imaging and therapy |
| UCK1/2 | Uridine-cytidine kinase, salvage of uridine and cytidine | Activates prodrugs like cytarabine; potential cancer target |
| DCK | Deoxycytidine kinase, salvage of deoxycytidine and analogs | Activates nucleoside analogs (e.g., gemcitabine); mutations cause resistance |
| CDA | Cytidine deaminase, deaminates cytidine and analogs | Influences response to cytarabine; polymorphisms affect toxicity |
| DPYD | Dihydropyrimidine dehydrogenase, rate-limiting enzyme in pyrimidine catabolism | Deficiency causes severe 5-fluorouracil toxicity; pharmacogenomic marker |
| DPYS | Dihydropyrimidinase, second step in pyrimidine catabolism | Deficiency causes dihydropyrimidinuria; neurological symptoms |
| UPB1 | Beta-ureidopropionase, final step in pyrimidine catabolism | Deficiency causes beta-ureidopropionase deficiency; metabolic disorder |
| PRPS1 | Phosphoribosyl pyrophosphate synthetase 1, provides PRPP for nucleotide synthesis | Mutations cause PRPS1 superactivity or Arts syndrome; links to purine and pyrimidine synthesis |
| NME1/2 | Nucleoside diphosphate kinases, interconvert NDPs and NTPs | Involved in metastasis suppression and nucleotide homeostasis |
| SLC29A1 | Equilibrative nucleoside transporter 1, imports nucleosides | Determines sensitivity to nucleoside analogs |
| SLC28A1/2/3 | Concentrative nucleoside transporters | Influence drug uptake and pyrimidine salvage |
| CMPK1 | Cytidine monophosphate kinase, phosphorylates CMP and UMP | Maintains pyrimidine nucleotide pools; potential target |
How Is pyrimidine nucleotide metabolic process Regulated?
Pyrimidine nucleotide metabolism is regulated at multiple levels to maintain cellular nucleotide pools. Allosteric feedback inhibition is a primary mechanism: UTP inhibits CAD, CTP inhibits CTPS, and UDP inhibits UMPS. Transcriptional regulation is linked to cell cycle progression and growth signals; the mTOR pathway promotes expression of pyrimidine biosynthetic enzymes to support proliferation. Post-translational modifications, such as phosphorylation of CAD by MAPK and mTORC1, modulate enzyme activity. In mitochondria, DHODH activity is coupled to the respiratory chain via ubiquinone, integrating pyrimidine synthesis with oxidative phosphorylation. In bacteria, pyrimidine-responsive regulators control gene expression in response to nucleotide availability.
pyrimidine nucleotide metabolic process and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| DPYD | Dihydropyrimidine dehydrogenase deficiency; severe 5-fluorouracil toxicity | Knockout or point-mutation knock-in in human cell lines; patient-derived organoids |
| UMPS | Hereditary orotic aciduria; anemia and developmental delay | Knockout in zebrafish or human iPSCs; rescue with uridine |
| DHODH | Cancer, autoimmune diseases, antiviral target; mitochondrial dysfunction | Knockout and overexpression in cancer cell lines; mitochondrial stress assays |
| CAD | Cancer proliferation; pyrimidine imbalance | CRISPR knockout in cancer cells; metabolomics and proliferation assays |
| CTPS1 | Immunodeficiency; impaired T and B cell proliferation | Knockout in Jurkat or primary lymphocytes; rescue with CTP |
Cancer
Many cancers exhibit upregulated de novo pyrimidine biosynthesis to support rapid proliferation. Enzymes such as CAD, DHODH, and TYMS are often overexpressed, and their inhibition can induce replication stress and cell death. DHODH inhibitors are in clinical trials for hematological malignancies and solid tumors. Additionally, pyrimidine nucleotide imbalance can trigger mitochondrial DNA-dependent innate immunity, which may influence tumor-immune interactions.
Inborn Errors of Metabolism
Deficiencies in pyrimidine catabolic enzymes (DPYD, DPYS, UPB1) cause rare metabolic disorders with neurological symptoms, and DPYD deficiency leads to severe toxicity to 5-fluorouracil. UMP synthase deficiency causes hereditary orotic aciduria, characterized by anemia and developmental delay. Splicing mutations in genes involved in nucleotide metabolism can also cause genetic disorders.
Antiviral and Antimicrobial Targeting
Many viruses depend on host pyrimidine nucleotide pools for replication, making the pathway a target for antiviral chemotherapy. Inhibitors of DHODH, such as brequinar and teriflunomide, show broad-spectrum antiviral activity. In bacteria, pyrimidine biosynthesis is essential, and differences from human enzymes make it an attractive target for new antibiotics.
Mitochondrial Dysfunction and Innate Immunity
Cellular pyrimidine imbalance can cause mitochondrial DNA release and activate innate immune responses via the cGAS-STING pathway. This link between nucleotide metabolism and immunity has implications for autoinflammatory diseases and cancer immunotherapy.
From pyrimidine nucleotide metabolic process-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Does loss of CAD impair cancer cell proliferation? | CRISPR knockout of CAD in cancer cell lines (e.g., HeLa, HCT116) followed by proliferation and metabolomics |
| Does a specific point mutation in DHODH alter enzyme activity? | CRISPR point mutation knock-in of DHODH variants in human cells; enzymatic assays |
| Can overexpression of UMPS rescue orotic aciduria phenotypes? | CRISPR knock-in of UMPS under a strong promoter in patient iPSCs or zebrafish |
| How does tagging endogenous CTPS1 affect its localization? | CRISPR knock-in of fluorescent or epitope tags at the CTPS1 locus; imaging and proteomics |
| What is the effect of DPYD deficiency on 5-FU toxicity? | CRISPR knockout of DPYD in hepatocyte-like cells; drug sensitivity assays |
| Which genes are synthetic lethal with DHODH inhibition? | Genome-wide CRISPR library screening in cancer cell lines treated with DHODH inhibitors |
How to Study the pyrimidine nucleotide metabolic process Process
| Method | What It Measures | Typical Application |
|---|---|---|
| LC-MS metabolomics | Quantification of pyrimidine nucleotides and intermediates | Assessing pool sizes in cancer cells or after drug treatment |
| CRISPR knockout screens | Gene essentiality and synthetic lethality | Identifying genes required for pyrimidine metabolism or drug sensitivity |
| Enzyme activity assays | Catalytic activity of specific enzymes | Characterizing mutant enzymes or testing inhibitors |
| Western blot and qPCR | Protein and mRNA expression levels | Validating knockout or overexpression models |
| Fluorescence microscopy | Subcellular localization of tagged proteins | Studying mitochondrial association of DHODH |
| Ribonucleotide reductase assay | dNTP pool measurement | Evaluating replication stress and DNA damage |
| CRISPR point mutation knock-in | Effect of specific mutations on enzyme function | Modeling patient variants in DPYD or UMPS |
| Zebrafish models | Developmental and metabolic phenotypes | Studying pyrimidine metabolism disorders in vivo |
Metabolomics and Nucleotide Pool Analysis
Liquid chromatography-mass spectrometry (LC-MS) and capillary electrophoresis-mass spectrometry (CE-MS) are used to quantify pyrimidine nucleotides (UMP, CMP, dTMP, UTP, CTP) in cells and tissues. These methods reveal pool sizes and fluxes, which are critical for understanding regulation and drug effects.
CRISPR Screens and Functional Genomics
Genome-wide CRISPR knockout or activation screens can identify genes that are essential for pyrimidine nucleotide metabolism or that mediate sensitivity to inhibitors like DHODH inhibitors. These screens link genotype to metabolic fitness and drug response.
Enzyme Activity Assays
Recombinant enzymes or cell lysates can be used to measure specific activities of CAD, DHODH, UMPS, CTPS, and others using spectrophotometric or radiometric assays. These assays help determine the impact of mutations or inhibitors.
Imaging and Subcellular Localization
Fluorescence microscopy of tagged enzymes (e.g., GFP-DHODH) or immunofluorescence can reveal subcellular localization and dynamics. Live-cell imaging can track mitochondrial association of DHODH and its response to metabolic stress.
How CRISPR Can Be Used to Study GO:0006220 pyrimidine nucleotide metabolic process
Knockout
CRISPR knockout of genes such as CAD, DHODH, or UMPS in human cell lines can reveal their essentiality for proliferation and survival. For example, knockout of DHODH in cancer cells leads to pyrimidine auxotrophy and can be rescued by exogenous uridine, demonstrating the pathway's role. Knockout models are also used to study drug sensitivity and metabolic reprogramming.
Point Mutation
CRISPR point mutation knock-in allows precise modeling of patient-derived missense mutations in genes like DPYD or UMPS. These models help determine whether a specific variant affects enzyme activity, stability, or drug response, providing functional evidence for clinical variants.
Knock-in
Knock-in of reporter tags (e.g., GFP, HA) or conditional alleles at endogenous loci enables real-time tracking of enzyme localization and dynamics. For example, tagging CTPS1 or DHODH can reveal their subcellular distribution and response to metabolic stress. Knock-in of wild-type or mutant cDNA can also rescue knockout phenotypes.
Overexpression
CRISPR activation (CRISPRa) or cDNA overexpression can elevate expression of pyrimidine biosynthetic enzymes to study their effects on nucleotide pools, proliferation, and drug resistance. Overexpression of CAD or DHODH may promote tumorigenesis or alter sensitivity to inhibitors.
How EDITGENE Supports pyrimidine nucleotide metabolic process Research
Researchers studying pyrimidine nucleotide metabolic process-related genes often need to determine whether a candidate gene is causally involved in metabolic regulation, disease progression, or drug response. Generating precise genetic models is essential to move from correlation to causation. EDITGENE provides a comprehensive suite of CRISPR-based services to accelerate this research.
Contact EDITGENE today to design your custom CRISPR model for pyrimidine nucleotide metabolic process research.
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| DCTD Knockout HEK293 Cell Line | EDJ-KQ3692 | Human | 1635 | Details Get a Quote |
| DCK Knockout HEK293 Cell Line | EDJ-KQ4426 | Human | 1633 | Details Get a Quote |
| CTPS2 Knockout HEK293 Cell Line | EDJ-KQ13050 | Human | 56474 | Details Get a Quote |
| ENPP3 Knockout HEK293 Cell Line | EDJ-KQ17752 | Human | 5169 | Details Get a Quote |
| DCK Knockout A-549 Cell Line | EDJ-KQ26962 | Human | 1633 | Details Get a Quote |
| DCK Knockout HCT 116 Cell Line | EDJ-KQ26963 | Human | 1633 | Details Get a Quote |
| DCK Knockout HeLa Cell Line | EDJ-KQ26964 | Human | 1633 | Details Get a Quote |
| DCTD Knockout A-549 Cell Line | EDJ-KQ26965 | Human | 1635 | Details Get a Quote |
| DCTD Knockout HCT 116 Cell Line | EDJ-KQ26967 | Human | 1635 | Details Get a Quote |
| DCTD Knockout HeLa Cell Line | EDJ-KQ26968 | Human | 1635 | Details Get a Quote |
| CTPS2 Knockout A-549 Cell Line | EDJ-KQ42322 | Human | 56474 | Details Get a Quote |
| CTPS2 Knockout HCT 116 Cell Line | EDJ-KQ42323 | Human | 56474 | Details Get a Quote |
| CTPS2 Knockout HeLa Cell Line | EDJ-KQ42324 | Human | 56474 | Details Get a Quote |
| ENPP3 Knockout HeLa Cell Line | EDJ-KQ54112 | Human | 5169 | Details Get a Quote |
| ENPP3 Knockout A-549 Cell Line | EDJ-KQ62600 | Human | 5169 | Details Get a Quote |
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Frequently Asked Questions About pyrimidine nucleotide metabolic process
What is pyrimidine nucleotide metabolic process (GO:0006220)?
It is the set of chemical reactions and pathways involving pyrimidine nucleotides, which are nucleosides with a pyrimidine base linked to ribose or deoxyribose and esterified with a phosphate group. This includes de novo synthesis, salvage, interconversion, and catabolism.
What genes are involved in pyrimidine nucleotide metabolism?
Key genes include CAD, DHODH, UMPS, CTPS1/2, RRM1/RRM2, TYMS, TK1, UCK1/2, DCK, CDA, DPYD, DPYS, and UPB1, among others.
Why is pyrimidine nucleotide metabolism important for cancer?
Cancer cells often upregulate de novo pyrimidine biosynthesis to support rapid proliferation. Inhibiting enzymes like DHODH or TYMS can induce replication stress and cell death, making them therapeutic targets.
How is pyrimidine nucleotide metabolism regulated?
It is regulated by allosteric feedback (e.g., UTP inhibits CAD, CTP inhibits CTPS), transcriptional control via mTOR and cell cycle signals, and post-translational modifications.
What diseases are associated with defects in pyrimidine metabolism?
Defects can cause hereditary orotic aciduria (UMPS), DPYD deficiency with severe 5-FU toxicity, dihydropyrimidinuria (DPYS), and beta-ureidopropionase deficiency (UPB1). Dysregulation is also linked to cancer and mitochondrial innate immunity.
How can CRISPR be used to study pyrimidine nucleotide metabolism?
CRISPR knockout, point mutation knock-in, tagged knock-in, and overexpression models allow causal testing of gene function, modeling patient variants, and identifying synthetic lethal interactions.
What model organisms are used to study pyrimidine metabolism?
Zebrafish are valuable for developmental and metabolic studies, and Pseudomonas species are used for bacterial pyrimidine regulation.
What methods measure pyrimidine nucleotide pools?
LC-MS and CE-MS metabolomics are commonly used to quantify nucleotides and intermediates in cells and tissues.
Is pyrimidine nucleotide metabolism a target for antiviral drugs?
Yes, many viruses depend on host pyrimidine pools, and inhibitors of DHODH and other enzymes show broad-spectrum antiviral activity.
How does pyrimidine imbalance trigger innate immunity?
Cellular pyrimidine imbalance can cause mitochondrial DNA release, which activates the cGAS-STING pathway and innate immune responses.
Conclusion
Pyrimidine nucleotide metabolic process (GO:0006220) is a fundamental biological pathway that supplies the building blocks for nucleic acids and supports diverse cellular functions. Its dysregulation is implicated in cancer, inborn errors of metabolism, and antiviral responses, making it a rich area for research. Advances in CRISPR-based models and metabolomics are enabling precise dissection of the pathway's genes and regulatory mechanisms. EDITGENE's comprehensive services can accelerate discoveries in this field by providing custom knockout, knock-in, point mutation, and overexpression models, as well as CRISPR screening and bioinformatics support.
References
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- 2. Anna A et al.. 2018. Splicing mutations in human genetic disorders: examples, detection, and confirmation.. J Appl Genet 59(3):253-268 PMID: 29680930
- 3. Chandel NS. 2021. Nucleotide Metabolism.. Cold Spring Harb Perspect Biol 13(7) PMID: 34210662
- 4. Bodampati S et al.. 2024. Pyrimidine Nucleotide Biosynthesis and Regulation in Pseudomonas lemonnieri.. Curr Microbiol 82(1):3 PMID: 39576324
- 5. Domakonda A et al.. 2020. Control of pyrimidine nucleotide formation in Pseudomonas aurantiaca.. Arch Microbiol 202(6):1551-1557 PMID: 32125450
- 6. Okesli A et al.. 2017. Human pyrimidine nucleotide biosynthesis as a target for antiviral chemotherapy.. Curr Opin Biotechnol 48:127-134 PMID: 28458037
- 7. Wang L. 2024. Zebrafish as a model for study of disorders in pyrimidine nucleotide metabolism.. Nucleosides Nucleotides Nucleic Acids 43(8):722-733 PMID: 38153103
- 8. Robinson AD et al.. 2020. Dysregulation of de novo nucleotide biosynthetic pathway enzymes in cancer and targeting opportunities.. Cancer Lett 470:134-140 PMID: 31733288
