Glyoxalase II does not support methylglyoxal detoxification but serves as a general trypanothione thioesterase in African trypanosomes
Wendler, Alexandra, Irsch, Thorsten, Rabbani, Naila, Thornalley, Paul J. and Krauth-Siegel, R. Luise. (2009) Glyoxalase II does not support methylglyoxal detoxification but serves as a general trypanothione thioesterase in African trypanosomes. Molecular and Biochemical Parasitology, Vol.163 (No.1). pp. 19-27. ISSN 0166-6851Full text not available from this repository.
Official URL: http://dx.doi.org/10.1016/j.molbiopara.2008.09.005
Glyoxalase I and II form a ubiquitous glutathione-dependent pathway for the detoxification of reactive and mutagenic ketoaldehydes. Methylglyoxal produced as spontaneous by-product of glycolysis is probably the main physiological substrate. Consequently, African trypanosomes with their exorbitant glucose turnover were expected to have a most efficient detoxification system. Trypanosoma brucei possesses a trypanothione [bis(glutathionyl)spermidine]-dependent glyoxalase II but lacks a glyoxalase I gene. Methylglyoxal reductase as well as dehydrogenase activities are negligible. However, the concentrations of methylglyoxal and advanced glycation end products in the parasites are similar to those in different mammalian cells and the mechanism of methylglyoxal elimination remains elusive.
Glyoxalase II is an abundant protein. Overexpression of the gene as well as RNA interference in bloodstream and procyclic cells did not result in a growth phenotype. Deletion of both alleles in procyclic parasites revealed that the enzyme is not essential at least under culture conditions. Recombinant glyoxalase II hydrolyzed the trypanothione-thioesters of methylglyoxal, glyoxal and 4,5-dioxovalerate, substrates of the classical glyoxalase system, with high efficiency. The absence of a glyoxalase I, however, renders these thioesters unlikely as physiological substrates. Here we show that trypanothione-thioesters can be generated from the respective coenzyme A derivative by transesterification. S-Acetyl- and S-prop ionyl trypanothione obtained by this spontaneous reaction proved to be excellent substrates of T brucei glyoxalase II. This offers a function for the parasite glyoxalase II as general trypanothione thioesterase independent of ketoaldehyde detoxification. Crown Copyright (C) 2008 Published by Elsevier B.V. All rights reserved.
|Item Type:||Journal Article|
|Subjects:||Q Science > QD Chemistry
Q Science > QL Zoology
|Divisions:||Faculty of Medicine > Warwick Medical School > Translational & Systems Medicine > Metabolic and Vascular Health
Faculty of Medicine > Warwick Medical School
|Journal or Publication Title:||Molecular and Biochemical Parasitology|
|Publisher:||Elsevier Science BV|
|Official Date:||January 2009|
|Number of Pages:||9|
|Page Range:||pp. 19-27|
|Access rights to Published version:||Restricted or Subscription Access|
|Funder:||Deutsche Forschungsgemeinschaft (DFG)|
|Grant number:||Kr 1242/4-1-2|
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