ArticleThe FEBS journal2009
A comparative study of methylglyoxal metabolism in trypanosomatids.
Article in The FEBS journal, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 74 citations in OpenAlex.
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- Comparative metabolism of conjugated and unconjugated pterins in Crithidia, Leishmania and African trypanosomes.PLoS neglected tropical diseases · 2025Article
- Pathogenicity and virulence of African trypanosomes: From laboratory models to clinically relevant hosts.Virulence · 2023Review
- Repurposing of rabeprazole as an anti-Journal of enzyme inhibition and medicinal chemistry · 2023Article
- Development of a 2,4-Diaminothiazole Series for the Treatment of Human African Trypanosomiasis Highlights the Importance of Static-Cidal Screening of Analogues.Journal of medicinal chemistry · 2023Article
- Metabolic Shades of S-D-Lactoylglutathione.Antioxidants (Basel, Switzerland) · 2022Review
- Nucleotide sugar biosynthesis occurs in the glycosomes of procyclic and bloodstream form Trypanosoma brucei.PLoS neglected tropical diseases · 2021Article
- Protein Lactylation Critically Regulates Energy Metabolism in the Protozoan ParasiteFrontiers in cell and developmental biology · 2021Article
- Genome-Wide Proteomics and Phosphoproteomics Analysis of Trypanosoma cruzi During Differentiation.Methods in molecular biology (Clifton, N.J.) · 2020Article
- Integrative Computational Framework for Understanding Metabolic Modulation in Leishmania.Frontiers in bioengineering and biotechnology · 2019Article
- Antitrypanosomatid Pharmacomodulation at Position 3 of the 8-Nitroquinolin-2(1H)-one Scaffold Using Palladium-Catalysed Cross-Coupling Reactions.ChemMedChem · 2018Article
- 8-Aryl-6-chloro-3-nitro-2-(phenylsulfonylmethyl)imidazo[1,2-a]pyridines as potent antitrypanosomatid molecules bioactivated by type 1 nitroreductases.European journal of medicinal chemistry · 2018Article
- A role for trypanosomatid aldo-keto reductases in methylglyoxal, prostaglandin and isoprostane metabolism.The Biochemical journal · 2018Article
- Genomic and transcriptomic alterations in Leishmania donovani lines experimentally resistant to antileishmanial drugs.International journal for parasitology. Drugs and drug resistance · 2018Article
- Novel 8-nitroquinolin-2(1H)-ones as NTR-bioactivated antikinetoplastid molecules: Synthesis, electrochemical and SAR study.European journal of medicinal chemistry · 2018Article
- Characterization ofBiotechnology for biofuels · 2018Article
- The N-myristoylome of Trypanosoma cruzi.Scientific reports · 2016Article
- Trypanosoma brucei DHFR-TS Revisited: Characterisation of a Bifunctional and Highly Unstable Recombinant Dihydrofolate Reductase-Thymidylate Synthase.PLoS neglected tropical diseases · 2016Article
- Nitroheterocyclic drug resistance mechanisms in Trypanosoma brucei.The Journal of antimicrobial chemotherapy · 2016Article
- Genomic and Proteomic Studies on the Mode of Action of Oxaboroles against the African Trypanosome.PLoS neglected tropical diseases · 2015Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
The glyoxalase system, comprising the metalloenzymes glyoxalase I (GLO1) and glyoxalase II (GLO2), is an almost universal metabolic pathway involved in the detoxification of the glycolytic byproduct methylglyoxal to d-lactate. In contrast to the situation with the trypanosomatid parasites Leishmania major and Trypanosoma cruzi, this trypanothione-dependent pathway is less well understood in the African trypanosome, Trypanosoma brucei. Although this organism possesses a functional GLO2, no apparent GLO1 gene could be identified in the T. brucei genome. The absence of GLO1 in T. brucei was confirmed by the lack of GLO1 activity in whole cell extracts, failure to detect a GLO1-like protein on immunoblots of cell lysates, and lack of d-lactate formation from methylglyoxal as compared to L. major and T. cruzi. T. brucei procyclics were found to be 2.4-fold and 5.7-fold more sensitive to methylglyoxal toxicity than T. cruzi and L. major, respectively. T. brucei also proved to be the least adept of the 'Tritryp' parasites in metabolizing methylglyoxal, producing l-lactate rather than d-lactate. Restoration of a functional glyoxalase system by expression of T. cruzi GLO1 in T. brucei resulted in increased resistance to methylglyoxal and increased conversion of methylglyoxal to d-lactate, demonstrating that GLO2 is functional in vivo. Procyclic forms of T. brucei possess NADPH-dependent methylglyoxal reductase and NAD(+)-dependent l-lactaldehyde dehydrogenase activities sufficient to account for all of the methylglyoxal metabolized by these cells. We propose that the predominant mechanism for methylglyoxal detoxification in the African trypanosome is via the methylglyoxal reductase pathway to l-lactate.
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