ArticleNature metabolism2019
NADPH production by the oxidative pentose-phosphate pathway supports folate metabolism.
Article in Nature metabolism, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 250 papers, 2 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
250 citing papers in PubMed, 2 syntheses or guidelines pooled it, 425 citations in OpenAlex.
- Purine xanthine oxidase inhibitors are not conducive to the prognosis of chronic heart failure: a meta-analysis.European journal of clinical pharmacology · 2025Pooled it
- Meta-analysis of NAD(P)(H) quantification results exhibits variability across mammalian tissues.Scientific reports · 2023Pooled it
- Plasma folate dynamics in Plasmodium falciparum-infected African children treated with artemisinin combination therapy and single low-dose primaquine or placebo.Malaria journal · 2025Trial
- The SLC7A11 Thermostat: A Molecular Signaling Switch Between Ferroptosis and Disulfidptosis in Neurodegenerative Disease.Molecular neurobiology · 2026Review
- Mitochondrial dysfunction drives metabolic reprogramming in Gitelman syndrome: insights from proteomics and isogenic modeling.Human genetics · 2026Article
- Metabolic circuitry of NADH buffering reveals a vulnerability in redox-adaptive cancer cells.Innovation (Cambridge (Mass.)) · 2026Article
- The Reductive Stress Nexus: Integrated Pathways of Metabolic Dysregulation, Senescence and Blood-Brain Barrier Failure in Neurodegenerative Disease and Brain Aging.Cell biochemistry and biophysics · 2026Review
- Disulfidptosis: Mechanisms, evidence boundaries, and translational opportunities.Redox biology · 2026Review
- AMPK Suppresses Multiple Forms of Cell Death Including Disulfidptosis in Tumor-Associated Macrophages During Tumor Progression.International journal of molecular sciences · 2026Article
- Disulfidptosis and its molecular mechanisms in cancer: mechanisms, regulation, and therapeutic potential.Medical oncology (Northwood, London, England) · 2026Review
- Redox-modulation of regulated cell death: implications for synergistic anticancer therapies.Naunyn-Schmiedeberg's archives of pharmacology · 2026Review
- Polyploid cancer cells surviving cisplatin reallocate central carbon sources to fuel antioxidant metabolism for survival.Molecular metabolism · 2026Article
- The Role of the Pentose Phosphate Pathway in Cardiovascular Diseases.Cardiovascular drugs and therapy · 2026Review
- Metal-organic framework nanoparticles induced non-apoptotic cell death: Construction, mechanisms, and cancer therapy.Materials today. Bio · 2026Review
- Simvastatin reprograms lipid metabolism in B16.F10 melanoma cells to favor an early resistant phenotype.Scientific reports · 2026Article
- Glucose-6-phosphate dehydrogenase (G6PD) deficiency is associated with elevated mean corpuscular volume (MCV) and bilirubin.BMC genomic data · 2026Article
- A Stable Isotope Tracing Primer for the Mass Spectrometrist.Annual review of analytical chemistry (Palo Alto, Calif.) · 2026Review
- Mitochondrial-Endothelial Crosstalk in Cardiometabolic Disease: Mechanisms and Translational Opportunities in the Multi-omics Era.Reviews in cardiovascular medicine · 2026Review
- Neuronal loss of the pentose phosphate pathway in the living nervous system is causally linked to [NADPH] reduction and elevated oxidative stress.The Journal of physiology · 2026Article
- Metabolic Reprogramming of Microglia in Neuroinflammation and Depression.International journal of molecular sciences · 2026Review
190 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
NADPH donates high energy electrons for antioxidant defense and reductive biosynthesis. Cytosolic NADP is recycled to NADPH by the oxidative pentose phosphate pathway (oxPPP), malic enzyme 1 (ME1) and isocitrate dehydrogenase 1 (IDH1). Here we show that any one of these routes can support cell growth, but the oxPPP is uniquely required to maintain a normal NADPH/NADP ratio, mammalian dihydrofolate reductase (DHFR) activity and folate metabolism. These findings are based on CRISPR deletions of glucose-6-phosphate dehydrogenase (G6PD, the committed oxPPP enzyme), ME1, IDH1, and combinations thereof in HCT116 colon cancer cells. Loss of G6PD results in high NADP, which induces compensatory increases in ME1 and IDH1 flux. But the high NADP inhibits dihydrofolate reductase (DHFR), resulting in impaired folate-mediated biosynthesis, which is reversed by recombinant expression of
Indexed as
Identifiers
31058257PMC6489125W2921800534What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.