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dc.contributor.author
Christodoulou, Dimitris
dc.contributor.author
Kuehne, Andreas
dc.contributor.author
Estermann, Alexandra
dc.contributor.author
Fuhrer, Tobias
dc.contributor.author
Lang, Paul
dc.contributor.author
Sauer, Uwe
dc.date.accessioned
2019-09-23T09:54:58Z
dc.date.available
2019-09-21T02:30:20Z
dc.date.available
2019-09-23T09:54:58Z
dc.date.issued
2019-09-27
dc.identifier.other
10.1016/j.isci.2019.08.047
en_US
dc.identifier.uri
http://hdl.handle.net/20.500.11850/365662
dc.identifier.doi
10.3929/ethz-b-000365662
dc.description.abstract
All organisms evolved defense mechanisms to counteract oxidative stress and buildup of reactive oxygen species (ROS). To test whether a potentially conserved mechanism exists for the rapid response, we investigated immediate metabolic dynamics of Escherichia coli, yeast, and human dermal fibroblasts to oxidative stress that we found to be conserved between species. To elucidate the regulatory mechanisms that implement this metabolic response, we developed mechanistic kinetic models for each organism's central metabolism and systematically tested activation and inactivation of each irreversible reaction by each metabolite. This ensemble modeling predicts in vivo relevant metabolite-enzyme interactions based on their ability to quantitatively describe metabolite dynamics. All three species appear to inhibit their oxidative pentose phosphate pathway during normal growth by the redox cofactor NADPH and relieve this inhibition to increase the pathway flux for detoxification of ROS during stress, with the sole exception of yeast when exposed to high levels of stress.
en_US
dc.language.iso
en
en_US
dc.publisher
Cell Press
en_US
dc.rights.uri
http://creativecommons.org/licenses/by/4.0/
dc.title
Reserve Flux Capacity in the Pentose Phosphate Pathway by NADPH Binding Is Conserved across Kingdoms
en_US
dc.type
Journal Article
dc.rights.license
Creative Commons Attribution 4.0 International
dc.date.published
2019-08-29
ethz.journal.title
iScience
ethz.journal.volume
19
en_US
ethz.pages.start
1133
en_US
ethz.pages.end
1144
en_US
ethz.version.deposit
publishedVersion
en_US
ethz.identifier.scopus
ethz.publication.place
Cambridge, MA
en_US
ethz.publication.status
published
en_US
ethz.date.deposited
2019-09-21T02:30:24Z
ethz.source
SCOPUS
ethz.eth
yes
en_US
ethz.availability
Open access
en_US
ethz.rosetta.installDate
2019-09-23T09:55:31Z
ethz.rosetta.lastUpdated
2019-09-23T09:55:31Z
ethz.rosetta.versionExported
true
ethz.COinS
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