期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 104, 期 40, 页码 15753-15758出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0707476104
关键词
gene-expression cascade; glycolysis; posttranscriptional regulation; regulation analysis; systems biology
资金
- Biotechnology and Biological Sciences Research Council [BB/C008219/1] Funding Source: Medline
- Biotechnology and Biological Sciences Research Council [BB/C008219/1] Funding Source: researchfish
Metabolic fluxes may be regulated hierarchically, e.g., by changes of gene expression that adjust enzyme capacities (V(max)) and/or metabolically by interactions of enzymes with substrates, products, or allosteric effectors. In the present study, a method is developed to dissect the hierarchical regulation into contributions by transcription, translation, protein degradation, and posttranslational modification. The method was applied to the regulation of fluxes through individual glycolytic enzymes when the yeast Saccharomyces cerevisiae was confronted with the absence of oxygen and the presence of benzoic acid depleting its ATIP. Metabolic regulation largely contributed to the approximate to 10-fold change in flux through the glycolytic enzymes. This contribution varied from 50 to 80%, depending on the glycolytic step and the cultivation condition tested. Within the 50-20% hierarchical regulation of fluxes, transcription played a minor role, whereas regulation of protein synthesis or degradation was the most important. These also contributed to 75-100% of the regulation of protein levels.
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