Evidence map›Paper›PMID 28388410›Full record

ArticleCell2017

Physiologic Medium Rewires Cellular Metabolism and Reveals Uric Acid as an Endogenous Inhibitor of UMP Synthase.

Jason R Cantor, Monther Abu-Remaileh, Naama Kanarek, Elizaveta Freinkman, Xin Gao, Abner Louissaint, Caroline A Lewis, David M Sabatini

Open access · bronzeAbstract read
In one paragraph

Article in Cell, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 392 papers.

0numbers the graph read from it
0cells of the map it votes in
392citing papers in PubMed
18.2field-weighted citation impact, top 1% 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

392 citing papers in PubMed, 648 citations in OpenAlex.

  1. Article
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  12. The GPX3-VCAM1 Axis Gates Pro-Fibrotic Tubule Cell Fate in Hyperuricemic Nephropathy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Article
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  14. Lactate Metabolism: Separating Correlation From Causation.BioEssays : news and reviews in molecular, cellular and developmental biology · 2026
    Review
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  16. Review
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332 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

8 authors at 7 institutions in 1 country.

Jason R CantorDepartment of Biology, Whitehead Institute for Biomedical Research and Massachusetts Institute of Technology, 9 Cambridge Center, Cambridge, MA 02142, USA; Department of Biology, Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Koch Institute for Integrative Cancer Research, 77 Massachusetts Avenue, Cambridge, MA 02139, USA; Broad Institute of Harvard and Massachusetts Institute of Technology, 7 Cambridge Center, Cambridge, MA 02142, USA.
Monther Abu-RemailehDepartment of Biology, Whitehead Institute for Biomedical Research and Massachusetts Institute of Technology, 9 Cambridge Center, Cambridge, MA 02142, USA; Department of Biology, Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Koch Institute for Integrative Cancer Research, 77 Massachusetts Avenue, Cambridge, MA 02139, USA; Broad Institute of Harvard and Massachusetts Institute of Technology, 7 Cambridge Center, Cambridge, MA 02142, USA.
Naama KanarekDepartment of Biology, Whitehead Institute for Biomedical Research and Massachusetts Institute of Technology, 9 Cambridge Center, Cambridge, MA 02142, USA; Department of Biology, Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Koch Institute for Integrative Cancer Research, 77 Massachusetts Avenue, Cambridge, MA 02139, USA; Broad Institute of Harvard and Massachusetts Institute of Technology, 7 Cambridge Center, Cambridge, MA 02142, USA.
Elizaveta FreinkmanDepartment of Biology, Whitehead Institute for Biomedical Research and Massachusetts Institute of Technology, 9 Cambridge Center, Cambridge, MA 02142, USA.
Xin GaoDepartment of Biology, Whitehead Institute for Biomedical Research and Massachusetts Institute of Technology, 9 Cambridge Center, Cambridge, MA 02142, USA; Beth Israel Deaconess Medical Center, Department of Medicine, Harvard Medical School, 330 Brookline Avenue, Boston, MA 02215, USA.
Abner LouissaintMassachusetts General Hospital, Department of Pathology, 55 Fruit Street, Boston, MA 02114, USA.
Caroline A LewisDepartment of Biology, Whitehead Institute for Biomedical Research and Massachusetts Institute of Technology, 9 Cambridge Center, Cambridge, MA 02142, USA.
David M SabatiniDepartment of Biology, Whitehead Institute for Biomedical Research and Massachusetts Institute of Technology, 9 Cambridge Center, Cambridge, MA 02142, USA; Department of Biology, Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Koch Institute for Integrative Cancer Research, 77 Massachusetts Avenue, Cambridge, MA 02139, USA; Broad Institute of Harvard and Massachusetts Institute of Technology, 7 Cambridge Center, Cambridge, MA 02142, USA. Electronic address: sabatini@wi.mit.edu.
Howard Hughes Medical Institute · USAllen Institute · USBeth Israel Deaconess Medical Center · USBroad Institute · USMassachusetts General Hospital · USMassachusetts Institute of Technology · USWhitehead Institute for Biomedical Research · US

Funding

Harvard Clinical and Translational Science CenterUL1TR001102 · NCATS · HARVARD MEDICAL SCHOOL · PI NADLER, LEE MARSHALL · 2013 to 2017
$106.2M
Regulation of the mTOR Pathway By NutrientsR01CA103866 · NCI · WHITEHEAD INSTITUTE FOR BIOMEDICAL RES · PI WEISSMAN, JONATHAN S. · 2004 to 2021
$7.0M
Novel Components of the mTORC1 and mTORC2 PathwaysR37AI047389 · NIAID · WHITEHEAD INSTITUTE FOR BIOMEDICAL RES · PI SABATINI, DAVID M. · 2010 to 2019
$4.8M
NCATS NIH HHS UL1 TR001102NCI NIH HHS R01 CA103866NIAID NIH HHS R37 AI047389
6 · The paper itself

Abstract

A complex interplay of environmental factors impacts the metabolism of human cells, but neither traditional culture media nor mouse plasma mimic the metabolite composition of human plasma. Here, we developed a culture medium with polar metabolite concentrations comparable to those of human plasma (human plasma-like medium [HPLM]). Culture in HPLM, relative to that in traditional media, had widespread effects on cellular metabolism, including on the metabolome, redox state, and glucose utilization. Among the most prominent was an inhibition of de novo pyrimidine synthesis-an effect traced to uric acid, which is 10-fold higher in the blood of humans than of mice and other non-primates. We find that uric acid directly inhibits uridine monophosphate synthase (UMPS) and consequently reduces the sensitivity of cancer cells to the chemotherapeutic agent 5-fluorouracil. Thus, media that better recapitulates the composition of human plasma reveals unforeseen metabolic wiring and regulation, suggesting that HPLM should be of broad utility.

Indexed as

AgedAnimalsCell Culture TechniquesCell Line, TumorCulture MediaFluorouracilGlucoseHumansLeukemia, Myeloid, AcuteMaleMiceMiddle AgedMultienzyme ComplexesOrotate PhosphoribosyltransferaseOrotidine-5'-Phosphate DecarboxylaseProtein DomainsCulture MediaFluorouracilGlucoseMultienzyme ComplexesOrotate PhosphoribosyltransferaseOrotidine-5'-Phosphate DecarboxylasepyrimidinePyrimidinesUric Aciduridine 5'-monophosphate synthasecell culturehuman-likemetabolismmetabolomicsplasmapyrimidine synthesisserumUMPSuric acid

Identifiers

PMID28388410
PMCPMC5421364
OpenAlexW2604353006

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

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.