Dynamic rerouting of the carbohydrate flux is key to counteracting oxidative stress
By M. Ralser, M. Wamelink, A. Kowald, Birgit Gerisch, G. Heeren, E. Struys, E. Klipp, C. Jakobs, M. Breitenbach, Hans Lehrach and 1 more. Journal of Biology, 2007
595 citations recorded by the source corpus.
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.
Subfields: Aging, Clinical Biochemistry, Molecular Biology
View Paper: https://www.semanticscholar.org/paper/ba46e7f222d80e6d43ce20ee42813a97906a6eb2
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In Aging
In Clinical Biochemistry
In Molecular Biology
- W. Moye-Rowley
- G. Koch
- C. Grant
- Scott C Thomas
- E. Schwartz
- Joshua D. Rabinowitz
- K. Morano
- P. Dijkstra
Citations in the corpus
- The Response to Heat Shock and Oxidative Stress in Saccharomyces cerevisiae (2012, background): “itant generation of NADPH, appears to be a conserved response to oxidative stress (Ralser et al. 2007).”
- Effect of temperature on metabolic activity of intact microbial communities: Evidence for altered metabolic pathway activity but not for increased maintenance respiration and reduced carbon use efficiency (2011, background): “This shift is thought to be in response to an increased NADPH demand needed to protect the cell against radical oxygen species (Ralser et al., 2007), increased pentose and NADPH demand for biosynthesis (Fuhrer and Sauer, 2009), or a way to maintain high Krebs cycle activity while circumventing tempe”
- The return of metabolism: biochemistry and physiology of the pentose phosphate pathway (2014, background): “These are highly dynamic and respond to changing endogenous and exogenous conditions by interactions of a specific and limited set of components (Ihmels, Levy & Barkai, 2004; Ralser et al., 2007; Chechik et al., 2008; Buescher et al., 2010; Fendt et al., 2010; Grüning, Lehrach & Ralser, 2010).”