ArticleNature communications2018
Serine synthesis through PHGDH coordinates nucleotide levels by maintaining central carbon metabolism.
Article in Nature communications, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 126 papers.
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Who cites it
126 citing papers in PubMed.
- Metabolic immune checkpoints (MICs) in cancer: from molecular mechanisms to challenges and opportunities in clinical translation.Signal transduction and targeted therapy · 2026Review
- Kiss and spit metabolomics highlight the role of host purine metabolism during pathogen infection.mSphere · 2026Article
- Multi-Stage transcriptomic dissection identifies key molecular determinants of chicken follicular development.Poultry science · 2026Article
- Cyclin-Dependent Kinases 4 and 6 Inhibitors: An Emerging Therapeutic Framework from Growth Suppression to Tumor Clearance.ACS pharmacology & translational science · 2026Review
- Reduced Myocardial Serine Synthesis Impairs Functional, Metabolic, and Redox Adaptations to Cardiac Stress.bioRxiv : the preprint server for biology · 2026Article
- Integrative multi-omics and machine learning reveal glycolysis-related biomarkers driving vascular remodeling in pulmonary arterial hypertension.Molecular and cellular biochemistry · 2026Article
- Proteomic Profiling of PTEN Inhibition on Periodontal Ligament Stem Cells.International dental journal · 2026Article
- Conserved principles of central carbon partitioning in Hippo-Yorkie-drivenbioRxiv : the preprint server for biology · 2026Article
- Article
- ADH1C Down-Regulation Is a Key Hypoxia Response in Colon Epithelium.The American journal of pathology · 2026Article
- Metabolic map of Brucellosis: From acute and chronic phase adaptation to targeted nanodrug design.Materials today. Bio · 2026Review
- PHGDH-mediated serine synthesis reduces oligodendrocyte death by sustaining GSH and NADPH levels after brain ischemia.Frontiers in pharmacology · 2026Article
- Beyond Protein Building Blocks: A Review of Biological Roles and Therapeutic Potential of Free Amino Acids.International journal of molecular sciences · 2025Review
- Functional Roles and Mechanistic Insights of YEATS Domain Proteins in Digestive System Tumors.Digestive diseases and sciences · 2025Review
- Respiration defects limit serine synthesis required for lung cancer growth and survival.Nature communications · 2025Article
- Comparative analysis of the effects of PSPH and PHGDH inhibitors on tumor cell proliferation.Investigational new drugs · 2025Article
- Multi-Omics and -Organ Insights into Energy Metabolic Adaptations in Early Sepsis Onset.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Serine synthesis pathway regulates cardiac differentiation from human pluripotent stem cells.iScience · 2025Article
- Role of amino acids in the regulation of hepatic gluconeogenesis and lipogenesis in metabolic dysfunctionassociated steatotic liver disease.Clinical and molecular hepatology · 2025Review
- Phosphoglycerate dehydrogenase is required for kernel development and defines a predominant serine synthesis pathway in maize.The Plant cell · 2025Article
66 more citing papers are in PubMed but not listed here.
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Authors and funding
12 authors.
Funding
Abstract
Phosphoglycerate dehydrogenase (PHGDH) catalyzes the committed step in de novo serine biosynthesis. Paradoxically, PHGDH and serine synthesis are required in the presence of abundant environmental serine even when serine uptake exceeds the requirements for nucleotide synthesis. Here, we establish a mechanism for how PHGDH maintains nucleotide metabolism. We show that inhibition of PHGDH induces alterations in nucleotide metabolism independent of serine utilization. These changes are not attributable to defects in serine-derived nucleotide synthesis and redox maintenance, another key aspect of serine metabolism, but result from disruption of mass balance within central carbon metabolism. Mechanistically, this leads to simultaneous alterations in both the pentose phosphate pathway and the tri-carboxylic acid cycle, as we demonstrate based on a quantitative model. These findings define a mechanism whereby disruption of one metabolic pathway induces toxicity by simultaneously affecting the activity of multiple related pathways.
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