Ralser2007_Carbohydrate_Rerouting_ROS

This is the model with unfitted
parameters described in the article
Dynamic rerouting of the carbohydrate flux is key to counteracting oxidative stress

Markus Ralser, Mirjam M Wamelink, Axel Kowald, Birgit Gerisch, Gino Heeren, Eduard A Struys, Edda Klipp, Cornelis Jakobs, Michael Breitenbach, Hans Lehrach and Sylvia Krobitsch, J Biol
2007 6(4):10; PMID: 18154684
, doi: 10.1186/jbiol61

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.
Different realtive enzyme velocities can be simulated by varying the parameters k_rel_TPI
and k_rel_GAPDH
.
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