Evidence map›Paper›PMID 28380375›Full record

ArticleCell metabolism2017

A Class of Reactive Acyl-CoA Species Reveals the Non-enzymatic Origins of Protein Acylation.

Gregory R Wagner, Dhaval P Bhatt, Thomas M O'Connell, J Will Thompson, Laura G Dubois, Donald S Backos, Hao Yang, Grant A Mitchell, Olga R Ilkayeva, Robert D Stevens and 2 more

Open access · bronzeAbstract read
In one paragraph

Article in Cell metabolism, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 163 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
163citing papers in PubMed, 1 pooled it
13.8field-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

163 citing papers in PubMed, 1 synthesis or guideline pooled it, 260 citations in OpenAlex.

  1. Pooled it
  2. HUNTER catches N-terminal prey of ICP55 in the mitochondria.Nature structural & molecular biology · 2026
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  18. Odd-Chain Dicarboxylic Acid Feeding Produces a Glutaric Aciduria Type 1-Like Metabolic Signature in Mice.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025
    Article
  19. Article
  20. Article

103 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

12 authors at 6 institutions in 3 countries.

Gregory R WagnerSarah W. Stedman Nutrition and Metabolism Center, Duke Molecular Physiology Institute, Duke University Medical Center, Durham, NC 27710, USA; Division of Endocrinology, Metabolism, and Nutrition, Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA.
Dhaval P BhattSarah W. Stedman Nutrition and Metabolism Center, Duke Molecular Physiology Institute, Duke University Medical Center, Durham, NC 27710, USA.
Thomas M O'ConnellSarah W. Stedman Nutrition and Metabolism Center, Duke Molecular Physiology Institute, Duke University Medical Center, Durham, NC 27710, USA.
J Will ThompsonDepartment of Pharmacology & Cancer Biology, Duke University Medical Center, Durham, NC 27710, USA; Duke Proteomics and Metabolomics Shared Resource, Duke University Medical Center, Durham, NC 27710, USA.
Laura G DuboisDuke Proteomics and Metabolomics Shared Resource, Duke University Medical Center, Durham, NC 27710, USA.
Donald S BackosComputational Chemistry and Biology Core Facility, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
Hao YangDivision of Medical Genetics, Department of Pediatrics, Université de Montréal and CHU Sainte-Justine, 3175 Côte Sainte-Catherine, Montreal, QC H3T 1C5, Canada; College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi 712100, China.
Grant A MitchellDivision of Medical Genetics, Department of Pediatrics, Université de Montréal and CHU Sainte-Justine, 3175 Côte Sainte-Catherine, Montreal, QC H3T 1C5, Canada.
Olga R IlkayevaSarah W. Stedman Nutrition and Metabolism Center, Duke Molecular Physiology Institute, Duke University Medical Center, Durham, NC 27710, USA.
Robert D StevensSarah W. Stedman Nutrition and Metabolism Center, Duke Molecular Physiology Institute, Duke University Medical Center, Durham, NC 27710, USA.
Paul A GrimsrudSarah W. Stedman Nutrition and Metabolism Center, Duke Molecular Physiology Institute, Duke University Medical Center, Durham, NC 27710, USA.
Matthew D HirscheySarah W. Stedman Nutrition and Metabolism Center, Duke Molecular Physiology Institute, Duke University Medical Center, Durham, NC 27710, USA; Division of Endocrinology, Metabolism, and Nutrition, Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA; Department of Pharmacology & Cancer Biology, Duke University Medical Center, Durham, NC 27710, USA. Electronic address: matthew.hirschey@duke.edu.
Duke University · USDuke University Hospital · USDuke Medical Center · USCentre Hospitalier Universitaire Sainte-Justine · CANorthwest A&F University · CNUniversity of Colorado Anschutz Medical Campus · US

Funding

Colorado Clinical and Translational Sciences InstituteUL1TR001082 · NCATS · UNIVERSITY OF COLORADO DENVER · PI SOKOL, RONALD J. · 2013 to 2017
$48.0M
Resource Core 3 - Metabolomics CoreP30AG028716 · NIA · DUKE UNIVERSITY · PI Sarah B. Peskoe · 2006 to 2026
$24.6M
Resource Section - Core 001U42OD010924 · OD · UNIV OF NORTH CAROLINA CHAPEL HILL · PI TERRY R MAGNUSON · 2012 to 2026
$24.5M
Endocrinology and Metabolism Training ProgramT32DK007012 · NIDDK · DUKE UNIVERSITY · PI DAVID A. D'ALESSIO · 1986 to 2026
$6.8M
Studies on the Mechanisms by which SIRT5 Regulates Aging and DiseaseR01AG045351 · NIA · DUKE UNIVERSITY · PI HIRSCHEY, MATTHEW D · 2014 to 2023
$4.4M
Ethanol-induced Protein Acylation Regulates MetabolismR01AA022146 · NIAAA · DUKE UNIVERSITY · PI FRITZ, KRISTOFER S, HIRSCHEY, MATTHEW D · 2013 to 2017
$2.3M
Novel SIRT4 Enzymatic Activity Influence Cellular Mechanisms of AgingR56AG052568 · NIA · DUKE UNIVERSITY · PI HIRSCHEY, MATTHEW D · 2016 to 2016
$398k
NCATS NIH HHS UL1 TR001082NIAAA NIH HHS R01 AA022146NIA NIH HHS P30 AG028716NIA NIH HHS R01 AG045351NIA NIH HHS R56 AG052568NIDDK NIH HHS T32 DK007012NIH HHS U42 OD010924
6 · The paper itself

Abstract

The mechanisms underlying the formation of acyl protein modifications remain poorly understood. By investigating the reactivity of endogenous acyl-CoA metabolites, we found a class of acyl-CoAs that undergo intramolecular catalysis to form reactive intermediates that non-enzymatically modify proteins. Based on this mechanism, we predicted, validated, and characterized a protein modification: 3-hydroxy-3-methylglutaryl(HMG)-lysine. In a model of altered HMG-CoA metabolism, we found evidence of two additional protein modifications: 3-methylglutaconyl(MGc)-lysine and 3-methylglutaryl(MG)-lysine. Using quantitative proteomics, we compared the "acylomes" of two reactive acyl-CoA species, namely HMG-CoA and glutaryl-CoA, which are generated in different pathways. We found proteins that are uniquely modified by each reactive metabolite, as well as common proteins and pathways. We identified the tricarboxylic acid cycle as a pathway commonly regulated by acylation and validated malate dehydrogenase as a key target. These data uncover a fundamental relationship between reactive acyl-CoA species and proteins and define a new regulatory paradigm in metabolism.

Indexed as

AcylationAcyl Coenzyme AAnhydridesBiocatalysisCitric Acid CycleLysineMetabolomeMitochondriaProtein Processing, Post-TranslationalProteinsProteomics3-hydroxy-3-methylglutaryl-coenzyme AAcyl Coenzyme AAnhydridesglutaryl-coenzyme ALysineProteinssuccinyl-coenzyme Aacyl-CoAchemical biologynon-enzymaticpost-translational modificationsprotein acylationsirtuins

Identifiers

PMID28380375
PMCPMC5399522
OpenAlexW2604275396

What OpenQuestion holds

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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.