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          Institute: MPI für molekulare Genetik     Collection: Department of Vertebrate Genomics     Display Documents



  history
ID: 335535.0, MPI für molekulare Genetik / Department of Vertebrate Genomics
Dynamic rerouting of the carbohydrate flux is key to counteracting oxidative stress
Authors:Ralser, Markus; Wamelink, Mirjam M.; Kowald, Axel; Gerisch, Birgit; Heeren, Gino; Struys, Eduard A.; Klipp, Edda; Jakobs, Cornelis; Breitenbach, Michael; Lehrach, H.; Krobitsch, Sylvia
Language:English
Date of Publication (YYYY-MM-DD):2007-12-21
Title of Journal:Journal of Biology
Journal Abbrev.:J Biol
Volume:6
Issue / Number:4
Start Page:10
End Page:10
Copyright:© 1999-2008 BioMed Central Ltd
Review Status:not specified
Audience:Experts Only
Abstract / Description:Background
Eukaryotic cells have evolved various response mechanisms to counteract the deleterious consequences of oxidative stress. Among these processes, metabolic alterations seem to play an important role.

Results
We recently discovered that yeast cells with reduced activity of the key glycolytic enzyme triosephosphate isomerase exhibit an increased resistance to the thiol-oxidizing reagent diamide. Here we show that this phenotype is conserved in Caenorhabditis elegans and that the underlying mechanism is based on a redirection of the metabolic flux from glycolysis to the pentose phosphate pathway, altering the redox equilibrium of the cytoplasmic NADP(H) pool. Remarkably, another key glycolytic enzyme, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), is known to be inactivated in response to various oxidant treatments, and we show that this provokes a similar redirection of the metabolic flux.

Conclusion
The naturally occurring inactivation of GAPDH functions as a metabolic switch for rerouting the carbohydrate flux to counteract oxidative stress. As a consequence, altering the homoeostasis of cytoplasmic metabolites is a fundamental mechanism for balancing the redox state of eukaryotic cells under stress conditions.
External Publication Status:published
Document Type:Article
Communicated by:Hans Lehrach
Affiliations:MPI für molekulare Genetik
External Affiliations:Department of Clinical Chemistry, Metabolic Unit, VU University Medical Center, Amsterdam, de Boelelaan 1117, 1081 HV Amsterdam, The Netherlands;
Department of Cell Biology, University of Salzburg, Hellbrunnerstrasse 34, 5020 Salzburg, Austria;
4Current address: Medical Proteome Center, Ruhr University Bochum, Universitätsstrasse 150, 44801 Bochum, Germany
Identifiers:ISSN:1475-4924
DOI:10.1186/jbiol61
URL:http://jbiol.com/content/pdf/jbiol61.pdf
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