Evidence map›Paper›PMID 25605736›Full record

ArticleThe Journal of biological chemistry2015

Quantitative analysis of purine nucleotides indicates that purinosomes increase de novo purine biosynthesis.

Hong Zhao, Christopher R Chiaro, Limin Zhang, Philip B Smith, Chung Yu Chan, Anthony M Pedley, Raymond J Pugh, Jarrod B French, Andrew D Patterson, Stephen J Benkovic

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 84 papers.

0numbers the graph read from it
0cells of the map it votes in
84citing papers in PubMed
5.1field-weighted citation impact, top 4% of its field
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

84 citing papers in PubMed, 125 citations in OpenAlex.

  1. Article
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  7. Coordination of cell organelles to promote metabolon formation.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  8. Review
  9. Article
  10. Resilience and Vulnerabilities of Tumor Cells under Purine Shortage Stress.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025
    Article
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  18. Review
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24 more citing papers are in PubMed but not listed here.

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 at 3 institutions in 2 countries.

Hong ZhaoFrom the Department of Chemistry.
Christopher R ChiaroMetabolomics Facility, Center for Molecular Toxicology and Carcinogenesis, and.
Limin ZhangMetabolomics Facility, Center for Molecular Toxicology and Carcinogenesis, and the CAS Key Laboratory of Magnetic Resonance in Biological Systems, State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, Wuhan Centre for Magnetic Resonance, Wuhan Institute of Physics and Mathematics, Chinese Academy of Sciences (CAS), Wuhan 430071, China, and.
Philip B SmithMetabolomics Facility, Center for Molecular Toxicology and Carcinogenesis, and.
Chung Yu ChanDepartment of Engineering Science and Mechanics, The Pennsylvania State University, University Park, Pennsylvania 16802.
Anthony M PedleyFrom the Department of Chemistry.
Raymond J PughFrom the Department of Chemistry.
Jarrod B Frenchthe Departments of Biochemistry and Cell Biology and Chemistry, Stony Brook University, Stony Brook, New York 11794.
Andrew D PattersonMetabolomics Facility, Center for Molecular Toxicology and Carcinogenesis, and adp117@psu.edu.
Stephen J BenkovicFrom the Department of Chemistry, sjb1@psu.edu.
Pennsylvania State University · USStony Brook University · USWuhan Institute of Physics and Mathematics · CN

Funding

TRANSFORMYLASE ENZYMES--DIHYDROFOLATE REDUCTASER01GM024129 · NIGMS · PENNSYLVANIA STATE UNIVERSITY-UNIV PARK · PI BENKOVIC, STEPHEN J · 1985 to 2024
$5.2M
Optimized Metabolite Extraction, Separation, and Identification for MetabolomicsR01ES022186 · NIEHS · PENNSYLVANIA STATE UNIVERSITY, THE · PI PATTERSON, ANDREW · 2012 to 2016
$2.0M
TRANSFORMYLASE ENZYMES/DIHYDROFOLATE REDUCTASER37GM024129 · NIGMS · PENNSYLVANIA STATE UNIVERSITY-UNIV PARK · PI BENKOVIC, STEPHEN J · 1987 to 1996
–
NIEHS NIH HHS ES022186NIEHS NIH HHS R01 ES022186NIGMS NIH HHS GM024129NIGMS NIH HHS R01 GM024129NIGMS NIH HHS R37 GM024129
6 · The paper itself

Abstract

Enzymes in the de novo purine biosynthesis pathway are recruited to form a dynamic metabolic complex referred to as the purinosome. Previous studies have demonstrated that purinosome assembly responds to purine levels in culture medium. Purine-depleted medium or 2-dimethylamino-4,5,6,7-tetrabromo-1H-benzimidazole (DMAT) treatment stimulates the purinosome assembly in HeLa cells. Here, several metabolomic technologies were applied to quantify the static cellular levels of purine nucleotides and measure the de novo biosynthesis rate of IMP, AMP, and GMP. Direct comparison of purinosome-rich cells (cultured in purine-depleted medium) and normal cells showed a 3-fold increase in IMP concentration in purinosome-rich cells and similar levels of AMP, GMP, and ratios of AMP/GMP and ATP/ADP for both. In addition, a higher level of IMP was also observed in HeLa cells treated with DMAT. Furthermore, increases in the de novo IMP/AMP/GMP biosynthetic flux rate under purine-depleted condition were observed. The synthetic enzymes, adenylosuccinate synthase (ADSS) and inosine monophosphate dehydrogenase (IMPDH), downstream of IMP were also shown to be part of the purinosome. Collectively, these results provide further evidence that purinosome assembly is directly related to activated de novo purine biosynthesis, consistent with the functionality of the purinosome.

Indexed as

Adenylosuccinate SynthaseBenzimidazolesCarbon-Nitrogen Ligases with Glutamine as Amide-N-DonorHeLa CellsHumansIMP DehydrogenaseMagnetic Resonance SpectroscopyMetabolomicsMultienzyme ComplexesPurine NucleotidesPurinesSpectrometry, Mass, Electrospray Ionization2-dimethylamino-4,5,6,7-tetrabromo-1H-benzimidazoleAdenylosuccinate SynthaseBenzimidazolesCarbon-Nitrogen Ligases with Glutamine as Amide-N-DonorIMP DehydrogenaseMultienzyme Complexesphosphoribosylformylglycinamidine synthetasepurinePurine NucleotidesPurinesMass Spectrometry (MS)Metabolic FluxMetabolomicsNucleoside/Nucleotide BiosynthesisProtein ComplexPurinePurinosome

Identifiers

PMID25605736
PMCPMC4358094
OpenAlexW2019502776

What OpenQuestion holds

Textmetadata
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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.