ArticleThe Journal of pharmacology and experimental therapeutics2008
Dehydroalanine analog of glutathione: an electrophilic busulfan metabolite that binds to human glutathione S-transferase A1-1.
Article in The Journal of pharmacology and experimental therapeutics, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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.
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.
Who cites it
18 citing papers in PubMed, 33 citations in OpenAlex.
- Response of Human Red Blood Cells to Acute and Chronic Oxidant Challenge as Observed Through the Glutathione and Glutathionyl-Hemoglobin Redox Pairs In Vitro and In Vivo.Molecules (Basel, Switzerland) · 2026Article
- Conversion of Ultrasmall Glutathione-Coated Silver Nanoparticles during Dispersion in Water into Ultrasmall Silver Sulfide Nanoparticles.Nanomaterials (Basel, Switzerland) · 2024Article
- Impact of valproic acid on busulfan pharmacokinetics: In vitro assessment of potential drug-drug interaction.PloS one · 2023Article
- Glutathione-Mediated Conjugation of Anticancer Drugs: An Overview of Reaction Mechanisms and Biological Significance for Drug Detoxification and Bioactivation.Molecules (Basel, Switzerland) · 2022Review
- Population pharmacokinetic model for once-daily intravenous busulfan in pediatric subjects describing time-associated clearance.CPT: pharmacometrics & systems pharmacology · 2022Article
- New insights into the mechanisms of age-related protein-protein crosslinking in the human lens.Experimental eye research · 2021Review
- Review of the Pharmacokinetics and Pharmacodynamics of Intravenous Busulfan in Paediatric Patients.Clinical pharmacokinetics · 2021Review
- DehydroalanylGly, a new post translational modification resulting from the breakdown of glutathione.Biochimica et biophysica acta. General subjects · 2018Article
- Clarifying busulfan metabolism and drug interactions to support new therapeutic drug monitoring strategies: a comprehensive review.Expert opinion on drug metabolism & toxicology · 2017Review
- Sulfheme formation during homocysteine S-oxygenation by catalase in cancers and neurodegenerative diseases.Nature communications · 2016Article
- Pharmacometabonomic Prediction of Busulfan Clearance in Hematopoetic Cell Transplant Recipients.Journal of proteome research · 2016Article
- The busulfan metabolite EdAG irreversibly glutathionylates glutaredoxins.Archives of biochemistry and biophysics · 2015Article
- Review
- Article
- A comparison of reversible versus irreversible protein glutathionylation.Advances in cancer research · 2014Article
- Intramolecular hydrogen transfer reactions of thiyl radicals from glutathione: formation of carbon-centered radical at Glu, Cys, and Gly.Chemical research in toxicology · 2012Article
- Reversible and irreversible protein glutathionylation: biological and clinical aspects.Expert opinion on drug metabolism & toxicology · 2011Review
- Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
Elimination of hydrogen sulfide from glutathione (GSH) converts a well known cellular nucleophile to an electrophilic species, gamma-glutamyldehydroalanylglycine (EdAG). We have found that a sulfonium metabolite formed from GSH and busulfan undergoes a facile beta-elimination reaction to give EdAG, which is an alpha,beta-unsaturated dehydroalanyl analog of GSH. EdAG was identified as a metabolite of busulfan in a human liver cytosol fraction. EdAG condenses with GSH in a Michael addition reaction to produce a lanthionine thioether [(2-amino-5-[[3-[2-[[4-amino-5-hydroxy-5-oxopentanoyl]amino]-3-(carboxymethylamino)-3-oxopropyl]sulfanyl-1-(carboxymethylamino)-1-oxopropan-2-yl]amino]-5-oxopentanoic acid); GSG], which is a nonreducible analog of glutathione disulfide. EdAG was less cytotoxic than busulfan to C6 rat glioma cells. GSH and EdAG were equally effective in displacing a glutathione S-transferase (GST) isozyme (human GSTA1-1) from a GSH-agarose column. The finding of an electrophilic metabolite of GSH suggests that alteration of cellular GSH concentrations, irreversible nonreducible glutathionylation of proteins, and interference with GST function may contribute to the toxicity of busulfan.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.