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PMID: 20393576 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

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

Molecular systems biology ·Vol. 6 ·2010-04-13 ·Pages 356

Fendt SM, Buescher JM, Rudroff F, Picotti P, Zamboni N, Sauer U

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.

MeSH Terms
Down-Regulation Enzymes/genetics,metabolism Gene Expression Profiling Gene Expression Regulation, Fungal Homeostasis Metabolic Networks and Pathways Models, Biological Reproducibility of Results Saccharomyces cerevisiae/genetics,metabolism Saccharomyces cerevisiae Proteins/genetics,metabolism Systems Biology/methods Transcription Factors/genetics,metabolism
Chemicals
Enzymes GCR2 protein, S cerevisiae Saccharomyces cerevisiae Proteins Transcription Factors
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Fendt Sarah-Maria
Institute of Molecular Systems Biology, ETH Zurich, Zurich, Switzerland.
Buescher Joerg Martin
Rudroff Florian
Picotti Paola
Zamboni Nicola
Sauer Uwe
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Article Info
Journal
Molecular systems biology
Abbr.
Mol Syst Biol
ISSN
1744-4292
DOI
10.1038/msb.2010.11
Published
2010-04-13
Pages
356
Language
English
Region
England
NLM ID
101235389
PMCID
PMC2872607
Subset
IM
External Links
PubMed source DOI: 10.1038/msb.2010.11 PMC Full Text View journal details
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