Evidence map›Paper›PMID 26667407›Full record

ArticleJournal of the American Chemical Society2016

Biosynthesis and Reactivity of Cysteine Persulfides in Signaling.

Pramod K Yadav, Michael Martinov, Victor Vitvitsky, Javier Seravalli, Rudolf Wedmann, Milos R Filipovic, Ruma Banerjee

Abstract read
In one paragraph

Article in Journal of the American Chemical Society, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 116 papers.

0numbers the graph read from it
0cells of the map it votes in
116citing papers in PubMed
15.1field-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

116 citing papers in PubMed, 243 citations in OpenAlex.

  1. Review
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  7. Self-bioRxiv : the preprint server for biology · 2026
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  12. The potential role of hydrogen sulfide-autophagy axis in diseases.Journal of physiology and biochemistry · 2025
    Review
  13. Profiling the landscape of cysteine posttranslational modifications in brain aging and neurodegeneration.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025
    Review
  14. Article
  15. Article
  16. Article
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  20. Review

56 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

7 authors at 4 institutions in 3 countries.

Pramod K YadavDepartment of Biological Chemistry, University of Michigan Medical School , Ann Arbor, Michigan 48109-0600, United States.
Michael MartinovCenter for Theoretical Problems of Physicochemical Pharmacology, Russian Academy of Sciences , Moscow 119991, Russia.
Victor VitvitskyDepartment of Biological Chemistry, University of Michigan Medical School , Ann Arbor, Michigan 48109-0600, United States.
Javier SeravalliDepartment of Biochemistry and the Redox Biology Center, University of Nebraska-Lincoln , Lincoln, Nebraska 68588, United States.
Rudolf WedmannDepartment of Chemistry and Pharmacy, Friedrich-Alexander University of Erlangen-Nuremberg , 91058 Erlangen, Germany.
Milos R FilipovicDepartment of Chemistry and Pharmacy, Friedrich-Alexander University of Erlangen-Nuremberg , 91058 Erlangen, Germany.
Ruma BanerjeeDepartment of Biological Chemistry, University of Michigan Medical School , Ann Arbor, Michigan 48109-0600, United States.
University of Michigan–Ann Arbor · USFriedrich-Alexander-Universität Erlangen-Nürnberg · DECenter for Theoretical Problems of Physicochemical Pharmacology · RUUniversity of Nebraska–Lincoln · US

Funding

Transsulfuration and HyperhomocysteinemiaR01HL058984 · NHLBI · UNIVERSITY OF NEBRASKA LINCOLN · PI BANERJEE, RUMA V · 1997 to 2020
$6.0M
NHLBI NIH HHS HL58984NHLBI NIH HHS R01 HL058984
6 · The paper itself

Abstract

Hydrogen sulfide (H2S) elicits pleiotropic physiological effects ranging from modulation of cardiovascular to CNS functions. A dominant method for transmission of sulfide-based signals is via posttranslational modification of reactive cysteine thiols to persulfides. However, the source of the persulfide donor and whether its relationship to H2S is as a product or precursor is controversial. The transsulfuration pathway enzymes can synthesize cysteine persulfide (Cys-SSH) from cystine and H2S from cysteine and/or homocysteine. Recently, Cys-SSH was proposed as the primary product of the transsulfuration pathway with H2S representing a decomposition product of Cys-SSH. Our detailed kinetic analyses demonstrate a robust capacity for Cys-SSH production by the human transsulfuration pathway enzymes, cystathionine beta-synthase and γ-cystathionase (CSE) and for homocysteine persulfide synthesis from homocystine by CSE only. However, in the reducing cytoplasmic milieu where the concentration of reduced thiols is significantly higher than of disulfides, substrate level regulation favors the synthesis of H2S over persulfides. Mathematical modeling at physiologically relevant hepatic substrate concentrations predicts that H2S rather than Cys-SSH is the primary product of the transsulfuration enzymes with CSE being the dominant producer. The half-life of the metastable Cys-SSH product is short and decomposition leads to a mixture of polysulfides (Cys-S-(S)n-S-Cys). These in vitro data, together with the intrinsic reactivity of Cys-SSH for cysteinyl versus sulfur transfer, are consistent with the absence of an observable increase in protein persulfidation in cells in response to exogenous cystine and evidence for the formation of polysulfides under these conditions.

Indexed as

Signal TransductionCells, CulturedChromatography, LiquidCysteineDisulfidesKineticsMass SpectrometryCysteinecysteine persulfideDisulfides

Identifiers

PMID26667407
PMCPMC4795164
OpenAlexW2316148924

What OpenQuestion holds

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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.