Tradeoff between enzyme and metabolite efficiency maintains metabolic homeostasis upon perturbations in enzyme capacity

Abstract What is the relationship between enzymes and metabolites, the two major constituents of metabolic networks? We propose three alternative relationships between enzyme capacity and metabolite concentration alterations based on a Michaelis–Menten kinetic; that is enzyme capacities, metabolite...

Full description

Saved in:
Bibliographic Details
Main Authors: Sarah‐Maria Fendt, Joerg Martin Buescher, Florian Rudroff, Paola Picotti, Nicola Zamboni, Uwe Sauer
Format: Article
Language:English
Published: Springer Nature 2010-04-01
Series:Molecular Systems Biology
Subjects:
Online Access:https://doi.org/10.1038/msb.2010.11
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1849225757106110464
author Sarah‐Maria Fendt
Joerg Martin Buescher
Florian Rudroff
Paola Picotti
Nicola Zamboni
Uwe Sauer
author_facet Sarah‐Maria Fendt
Joerg Martin Buescher
Florian Rudroff
Paola Picotti
Nicola Zamboni
Uwe Sauer
author_sort Sarah‐Maria Fendt
collection DOAJ
description Abstract What is the relationship between enzymes and metabolites, the two major constituents of metabolic networks? We propose three alternative relationships between enzyme capacity and metabolite concentration alterations based on a Michaelis–Menten kinetic; that is enzyme capacities, metabolite concentrations, or both could limit the metabolic reaction rates. These relationships imply different correlations between changes in enzyme capacity and metabolite concentration, which we tested by quantifying metabolite, transcript, and enzyme abundances upon local (single‐enzyme modulation) and global (GCR2 transcription factor mutant) perturbations in Saccharomyces cerevisiae. Our results reveal an inverse relationship between fold‐changes in substrate metabolites and their catalyzing enzymes. These data provide evidence for the hypothesis that reaction rates are jointly limited by enzyme capacity and metabolite concentration. Hence, alteration in one network constituent can be efficiently buffered by converse alterations in the other constituent, implying a passive mechanism to maintain metabolic homeostasis upon perturbations in enzyme capacity.
format Article
id doaj-art-4381c931a8a34df2be583626db6bcb0d
institution Kabale University
issn 1744-4292
language English
publishDate 2010-04-01
publisher Springer Nature
record_format Article
series Molecular Systems Biology
spelling doaj-art-4381c931a8a34df2be583626db6bcb0d2025-08-24T12:00:48ZengSpringer NatureMolecular Systems Biology1744-42922010-04-016111110.1038/msb.2010.11Tradeoff between enzyme and metabolite efficiency maintains metabolic homeostasis upon perturbations in enzyme capacitySarah‐Maria Fendt0Joerg Martin Buescher1Florian Rudroff2Paola Picotti3Nicola Zamboni4Uwe Sauer5Institute of Molecular Systems BiologyInstitute of Molecular Systems BiologyInstitute of Molecular Systems BiologyInstitute of Molecular Systems BiologyInstitute of Molecular Systems BiologyInstitute of Molecular Systems BiologyAbstract What is the relationship between enzymes and metabolites, the two major constituents of metabolic networks? We propose three alternative relationships between enzyme capacity and metabolite concentration alterations based on a Michaelis–Menten kinetic; that is enzyme capacities, metabolite concentrations, or both could limit the metabolic reaction rates. These relationships imply different correlations between changes in enzyme capacity and metabolite concentration, which we tested by quantifying metabolite, transcript, and enzyme abundances upon local (single‐enzyme modulation) and global (GCR2 transcription factor mutant) perturbations in Saccharomyces cerevisiae. Our results reveal an inverse relationship between fold‐changes in substrate metabolites and their catalyzing enzymes. These data provide evidence for the hypothesis that reaction rates are jointly limited by enzyme capacity and metabolite concentration. Hence, alteration in one network constituent can be efficiently buffered by converse alterations in the other constituent, implying a passive mechanism to maintain metabolic homeostasis upon perturbations in enzyme capacity.https://doi.org/10.1038/msb.2010.11design principlemetabolic networkmetabolomicsproteomicstranscriptome
spellingShingle Sarah‐Maria Fendt
Joerg Martin Buescher
Florian Rudroff
Paola Picotti
Nicola Zamboni
Uwe Sauer
Tradeoff between enzyme and metabolite efficiency maintains metabolic homeostasis upon perturbations in enzyme capacity
Molecular Systems Biology
design principle
metabolic network
metabolomics
proteomics
transcriptome
title Tradeoff between enzyme and metabolite efficiency maintains metabolic homeostasis upon perturbations in enzyme capacity
title_full Tradeoff between enzyme and metabolite efficiency maintains metabolic homeostasis upon perturbations in enzyme capacity
title_fullStr Tradeoff between enzyme and metabolite efficiency maintains metabolic homeostasis upon perturbations in enzyme capacity
title_full_unstemmed Tradeoff between enzyme and metabolite efficiency maintains metabolic homeostasis upon perturbations in enzyme capacity
title_short Tradeoff between enzyme and metabolite efficiency maintains metabolic homeostasis upon perturbations in enzyme capacity
title_sort tradeoff between enzyme and metabolite efficiency maintains metabolic homeostasis upon perturbations in enzyme capacity
topic design principle
metabolic network
metabolomics
proteomics
transcriptome
url https://doi.org/10.1038/msb.2010.11
work_keys_str_mv AT sarahmariafendt tradeoffbetweenenzymeandmetaboliteefficiencymaintainsmetabolichomeostasisuponperturbationsinenzymecapacity
AT joergmartinbuescher tradeoffbetweenenzymeandmetaboliteefficiencymaintainsmetabolichomeostasisuponperturbationsinenzymecapacity
AT florianrudroff tradeoffbetweenenzymeandmetaboliteefficiencymaintainsmetabolichomeostasisuponperturbationsinenzymecapacity
AT paolapicotti tradeoffbetweenenzymeandmetaboliteefficiencymaintainsmetabolichomeostasisuponperturbationsinenzymecapacity
AT nicolazamboni tradeoffbetweenenzymeandmetaboliteefficiencymaintainsmetabolichomeostasisuponperturbationsinenzymecapacity
AT uwesauer tradeoffbetweenenzymeandmetaboliteefficiencymaintainsmetabolichomeostasisuponperturbationsinenzymecapacity