title: 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 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.
authors.affiliation: Institute of Molecular Systems Biology, ETH Zurich, Zurich, Switzerland.
authors.forename: Sarah-Maria
authors.initials: SM
authors.lastname: Fendt
authors.forename: Joerg Martin
authors.initials: JM
authors.lastname: Buescher
authors.forename: Florian
authors.initials: F
authors.lastname: Rudroff
authors.forename: Paola
authors.initials: P
authors.lastname: Picotti
authors.forename: Nicola
authors.initials: N
authors.lastname: Zamboni
authors.forename: Uwe
authors.initials: U
authors.lastname: Sauer
mesh_terms: D015536:Down-Regulation; D004798:Enzymes / Q000235:genetics / Q000378:metabolism*; D020869:Gene Expression Profiling; D015966:Gene Expression Regulation, Fungal; D006706:Homeostasis; D053858:Metabolic Networks and Pathways; D008954:Models, Biological; D015203:Reproducibility of Results; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism; D049490:Systems Biology / Q000379:methods*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D004798:Enzymes; C076228:GCR2 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors
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