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

被引:130
作者
Fendt, Sarah-Maria [1 ,2 ,3 ]
Buescher, Joerg Martin [1 ,4 ]
Rudroff, Florian [1 ]
Picotti, Paola [1 ]
Zamboni, Nicola [1 ,3 ]
Sauer, Uwe [1 ,3 ]
机构
[1] ETH, Inst Mol Syst Biol, CH-8093 Zurich, Switzerland
[2] Life Sci Zurich PhD Program Syst Biol Complex Dis, Zurich, Switzerland
[3] Competence Ctr Syst Physiol & Metab Dis, Zurich, Switzerland
[4] Life Sci Zurich PhD Program Mol Life Sci, Zurich, Switzerland
基金
美国国家科学基金会;
关键词
design principle; metabolic network; metabolomics; proteomics; transcriptome; GLYCOLYTIC GENE-EXPRESSION; SACCHAROMYCES-CEREVISIAE; TRANSCRIPTIONAL REGULATION; MASS-SPECTROMETRY; LINEAR TREATMENT; YEAST; FLUX; GROWTH; MUTANTS; PATHWAY;
D O I
10.1038/msb.2010.11
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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. Molecular Systems Biology 6: 356; published online 13 April 2010; doi:10.1038/msb.2010.11
引用
收藏
页数:11
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