Evidence map›Paper›PMID 34385458›Full record

ArticleNature communications2021

Spontaneous hydrolysis and spurious metabolic properties of α-ketoglutarate esters.

Seth J Parker, Joel Encarnación-Rosado, Kate E R Hollinshead, David M Hollinshead, Leonard J Ash, Juan A K Rossi, Elaine Y Lin, Albert S W Sohn, Mark R Philips, Drew R Jones and 1 more

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed
2.1field-weighted citation impact, top 12% 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

28 citing papers in PubMed, 36 citations in OpenAlex.

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  10. Loss of vitamin C biosynthesis protects from the pathology of a parasitic infection.Proceedings of the National Academy of Sciences of the United States of America · 2025
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  14. Activity-Based Acylome Profiling withJournal of the American Chemical Society · 2024
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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

11 authors at 2 institutions in 2 countries.

Seth J ParkerDepartment of Radiation Oncology, New York University School of Medicine, New York, NY, USA. seth.parker@bcchr.ca.ORCID 0000-0001-7971-8848
Joel Encarnación-RosadoDepartment of Radiation Oncology, New York University School of Medicine, New York, NY, USA.
Kate E R Hollinshead *Department of Radiation Oncology, New York University School of Medicine, New York, NY, USA.
David M Hollinshead *Elixir Software Ltd., Macclesfield, Cheshire, UK.
Leonard J AshDivision of Advanced Research Technologies, New York University School of Medicine, New York, NY, USA.
Juan A K RossiPerlmutter Cancer Center, New York University School of Medicine, New York, NY, USA.
Elaine Y LinDepartment of Radiation Oncology, New York University School of Medicine, New York, NY, USA.
Albert S W SohnDepartment of Radiation Oncology, New York University School of Medicine, New York, NY, USA.
Mark R PhilipsPerlmutter Cancer Center, New York University School of Medicine, New York, NY, USA.ORCID 0000-0002-1179-8156
Drew R JonesDivision of Advanced Research Technologies, New York University School of Medicine, New York, NY, USA.
Alec C KimmelmanDepartment of Radiation Oncology, New York University School of Medicine, New York, NY, USA. alec.kimmelman@nyulangone.org.
New York University · USUniversity of British Columbia · CA

Funding

Vaccine FacilityP30CA016087 · NCI · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI ADRIANA HEGUY · 1985 to 2026
$83.1M
The RAS and P13K Pathways in Pancreatic AdenocarcinomaP01CA117969 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI DEPINHO, RONALD ANTHONY · 2006 to 2025
$41.7M
Identifying Metabolic Dependencies of Pancreatic CancersR35CA232124 · NCI · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI KIMMELMAN, ALEC · 2018 to 2024
$6.5M
Network organization of the human autophagy systemR01GM095567 · NIGMS · HARVARD MEDICAL SCHOOL · PI HARPER, JEFFREY W, KIMMELMAN, ALEC · 2011 to 2018
$3.0M
Investigating the Role of Autophagy in Pancreatic Cancer Radiation ResistanceR01CA157490 · NCI · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI KIMMELMAN, ALEC · 2011 to 2018
$2.5M
Investigating a Novel Glutamine Metabolism Pathway in Pancreatic CancerR01CA188048 · NCI · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI KIMMELMAN, ALEC · 2015 to 2018
$1.5M
NCI NIH HHS P01 CA117969NCI NIH HHS P30 CA016087NCI NIH HHS R01 CA157490NCI NIH HHS R01 CA188048NCI NIH HHS R35 CA232124NIGMS NIH HHS R01 GM095567
6 · The paper itself

Abstract

α-ketoglutarate (KG), also referred to as 2-oxoglutarate, is a key intermediate of cellular metabolism with pleiotropic functions. Cell-permeable esterified analogs are widely used to study how KG fuels bioenergetic and amino acid metabolism and DNA, RNA, and protein hydroxylation reactions, as cellular membranes are thought to be impermeable to KG. Here we show that esterified KG analogs rapidly hydrolyze in aqueous media, yielding KG that, in contrast to prevailing assumptions, imports into many cell lines. Esterified KG analogs exhibit spurious KG-independent effects on cellular metabolism, including extracellular acidification, arising from rapid hydrolysis and de-protonation of α-ketoesters, and significant analog-specific inhibitory effects on glycolysis or mitochondrial respiration. We observe that imported KG decarboxylates to succinate in the cytosol and contributes minimally to mitochondrial metabolism in many cell lines cultured in normal conditions. These findings demonstrate that nuclear and cytosolic KG-dependent reactions may derive KG from functionally distinct subcellular pools and sources.

Indexed as

Energy MetabolismAmino AcidsAnimalsCell Line, TumorCytosolEstersGlycolysisHEK293 CellsHumansHydrolysisHydrophobic and Hydrophilic InteractionsKetoglutaric AcidsMiceMitochondriaOxygen ConsumptionRAW 264.7 CellsAmino AcidsEstersKetoglutaric AcidsSuccinic Acid

Identifiers

PMID34385458
PMCPMC8361106
OpenAlexW3192478464

What OpenQuestion holds

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LicenceCC BY
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.