Evidence mapPaperPMID 40437135Full record

ArticleNature chemical biology2025

Reactivity-based metabolomics reveal cysteine has glyoxalase 1-like and glyoxalase 2-like activities.

Marc Daniel Opfermann, Maria Bøgelund Søndergård, Louise Vase Bech, Camilla B Nielsen, Alejandro Mahía, Charlotte Brinck Holt, Tingting Wang, Sarah Bisgaard Olesen, Kim Frisch, Jakob Appel Østergaard and 6 more

Abstract read
In one paragraph

Article in Nature chemical biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing 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

4 citing papers in PubMed.

  1. Article
  2. Review
  3. Article
  4. 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

16 authors.

Marc Daniel Opfermann *Department of Forensic Medicine, Aarhus University, Aarhus, Denmark.
Maria Bøgelund Søndergård *Department of Forensic Medicine, Aarhus University, Aarhus, Denmark.
Louise Vase BechDepartment of Forensic Medicine, Aarhus University, Aarhus, Denmark.
Camilla B NielsenDepartment of Forensic Medicine, Aarhus University, Aarhus, Denmark.
Alejandro MahíaDepartment of Chemistry, Aarhus University, Aarhus, Denmark.
Charlotte Brinck HoltSteno Diabetes Center Aarhus, Aarhus University Hospital, Aarhus, Denmark.ORCID http://orcid.org/0000-0002-7503-5879
Tingting WangDepartment of Forensic Medicine, Aarhus University, Aarhus, Denmark.ORCID http://orcid.org/0000-0002-9100-3447
Sarah Bisgaard OlesenDepartment of Forensic Medicine, Aarhus University, Aarhus, Denmark.
Kim FrischDepartment of Forensic Medicine, Aarhus University, Aarhus, Denmark.ORCID http://orcid.org/0000-0001-9691-2853
Jakob Appel ØstergaardSteno Diabetes Center Aarhus, Aarhus University Hospital, Aarhus, Denmark.ORCID http://orcid.org/0000-0002-9877-5327
Dieter BritzDepartment of Chemistry, Aarhus University, Aarhus, Denmark.
Kirstine Lykke NielsenDepartment of Forensic Medicine, Aarhus University, Aarhus, Denmark.ORCID http://orcid.org/0000-0002-5955-6156
James J GalliganDepartment of Pharmacology and Toxicology, University of Arizona, Tucson, AZ, USA.ORCID http://orcid.org/0000-0002-5612-0680
Thomas B PoulsenDepartment of Chemistry, Aarhus University, Aarhus, Denmark.ORCID http://orcid.org/0000-0002-0763-9996
Jakob Hansen *Department of Forensic Medicine, Aarhus University, Aarhus, Denmark.
Mogens JohannsenDepartment of Forensic Medicine, Aarhus University, Aarhus, Denmark. mj@forens.au.dk.ORCID http://orcid.org/0000-0002-2548-7025

Funding

Glyoxalase 1 and its Role in Metabolic SyndromeR01DK133196 · UNIVERSITY OF ARIZONA · 2025 to 2025
$466k
NIDDK NIH HHS R01 DK133196NIGMS NIH HHS R35 GM137910Novo Nordisk Fonden (Novo Nordisk Foundation) NNF20OC0065548
6 · The paper itself

Abstract

Methylglyoxal (MG) is a reactive metabolite involved in diabetes and aging through the formation of protein adducts. Less is known about the extent that MG and its metabolic product S-D-lactoylglutathione (LGSH) form adducts with cell metabolites. Using a 'symmetric' isotope-labeled and reactivity-based metabolomics approach in living cells, we found over 200 adducts and, surprisingly, discovered that 10 of the most abundant are lactoylated amino acids mainly derived from LGSH. The most abundant adduct D-Lac-Cys is formed rapidly between LGSH and cysteine, whereas the diastereoisomer L-Lac-Cys is formed directly from MG and cysteine, assigning cysteine with both glyoxalase 1-like and glyoxalase 2-like activity. Cellular cysteine and MG dynamically regulate D-Lac-Cys and L-Lac-Cys levels and the adducts are increased in diabetes, suggesting their use as novel biomarkers. Lastly, cysteine amides, as proxies for protein cysteines, also undergo lactoylation by MG and LGSH, suggesting the existence of two additional pathways for nonenzymatic lactoylation of proteins.

Indexed as

CysteineLactoylglutathione LyaseMetabolomicsThiolester HydrolasesAnimalsHumansHydroxyacylglutathione HydrolasePyruvaldehydeCysteineGLO1 protein, humanHydroxyacylglutathione HydrolaseLactoylglutathione LyasePyruvaldehydeThiolester Hydrolases

Identifiers

PMID40437135
PMCPMC12921598

What Socratic 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 Socratic graph.