X-Message-Number: 30218
From: David Stodolsky <>
Subject: Dynamic rerouting of the carbohydrate flux is key to countera...
Date: Thu, 27 Dec 2007 09:54:06 +0100

http://jbiol.com/content/6/4/10


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

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.



  2007 Ralser et al.; licensee BioMed Central Ltd.
This is an Open Access article distributed under the terms of the  
Creative Commons Attribution License (http://creativecommons.org/ 
licenses/by/2.0), which permits unrestricted use, distribution, and  
reproduction in any medium, provided the original work is properly  
cited.



David Stodolsky    Skype: davidstodolsky

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