期刊
MOLECULAR SYSTEMS BIOLOGY
卷 6, 期 -, 页码 -出版社
WILEY
DOI: 10.1038/msb.2010.11
关键词
design principle; metabolic network; metabolomics; proteomics; transcriptome
资金
- Competence Center for Systems Physiology and Metabolic Diseases
- EU [LSHG-CT-2006-037469]
- FWF Schrodinger Stipendium
- intra-European Marie Curie Fellowship
- Direct For Biological Sciences
- Div Of Biological Infrastructure [0805648] Funding Source: National Science Foundation
- Division of Computing and Communication Foundations
- Direct For Computer & Info Scie & Enginr [832824] Funding Source: National Science Foundation
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
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