Evidence map›Paper›PMID 40450004›Full record

ArticleNature communications2025

Charting unknown metabolic reactions by mass spectrometry-resolved stable-isotope tracing metabolomics.

Yang Gao, Mingdu Luo, Hongmiao Wang, Zhiwei Zhou, Yandong Yin, Ruohong Wang, Beizi Xing, Xiaohua Yang, Yuping Cai, Zheng-Jiang Zhu

Abstract read
In one paragraph

Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

13 citing papers in PubMed.

  1. Article
  2. Review
  3. Leveraging 13C-Labeling to Assign Molecular Formulas to Unknown Yeast Metabolites.Journal of the American Society for Mass Spectrometry · 2026
    Article
  4. Mapping the mammalian dark metabolome bybioRxiv : the preprint server for biology · 2026
    Article
  5. Review
  6. Article
  7. Large-Scale Metabolite Annotation in Untargeted Metabolomics Using MetDNA.Methods in molecular biology (Clifton, N.J.) · 2026
    Article
  8. Urinary metabolome dynamics inMetabolomics : Official journal of the Metabolomic Society · 2025
    Article
  9. Review
  10. Review
  11. Review
  12. Article
  13. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors.

Yang GaoInterdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai, China.
Mingdu LuoInterdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai, China.
Hongmiao WangInterdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai, China.
Zhiwei ZhouInterdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai, China.ORCID http://orcid.org/0000-0002-1249-6870
Yandong YinInterdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai, China.
Ruohong WangInterdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai, China.
Beizi XingInterdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai, China.
Xiaohua YangInterdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai, China.
Yuping CaiInterdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai, China. yupingcai@sioc.ac.cn.ORCID http://orcid.org/0000-0002-5701-3609
Zheng-Jiang ZhuInterdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai, China. jiangzhu@sioc.ac.cn.ORCID http://orcid.org/0000-0002-3272-3567

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Metabolic reactions play important roles in organisms such as providing energy, transmitting signals, and synthesizing biomacromolecules. Charting unknown metabolic reactions in cells is hindered by limited technologies, restricting the holistic understanding of cellular metabolism. Using mass spectrometry-resolved stable-isotope tracing metabolomics, we develop an isotopologue similarity networking strategy, namely IsoNet, to effectively deduce previously unknown metabolic reactions. The strategy uncovers ~300 previously unknown metabolic reactions in living cells and mice. Specifically, we elaborately chart the metabolic reaction network related to glutathione, unveiling three previously unreported reactions nestled within glutathione metabolism. Among these, a transsulfuration reaction, synthesizing γ-glutamyl-seryl-glycine directly from glutathione, underscores the role of glutathione as a sulfur donor. Functional metabolomics studies systematically characterize biochemical effects of previously unknown reactions in glutathione metabolism, showcasing their diverse functions in regulating cellular metabolism. Overall, these newly uncovered metabolic reactions fill gaps in the metabolic network maps, facilitating exploration of uncharted territories in cellular biochemistry.

Indexed as

Isotope LabelingMass SpectrometryMetabolic Networks and PathwaysMetabolomicsAnimalsGlutathioneHumansMetabolomeMiceGlutathione

Identifiers

PMID40450004
PMCPMC12126588

What OpenQuestion holds

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LicenceCC BY-NC-ND
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Registered trials

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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.