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J Biol. 2007 Dec 21;6(4):10.

Dynamic rerouting of the carbohydrate flux is key to counteracting oxidative stress.

Author information

1
Max Planck Institute for Molecular Genetics, Ihnestrasse 73, 14195 Berlin, Germany. ralser@molgen.mpg.de

Abstract

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.

PMID:
18154684
PMCID:
PMC2373902
DOI:
10.1186/jbiol61
[Indexed for MEDLINE]
Free PMC Article

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