The fluxes through glycolytic enzymes in Saccharomyces cerevisiae are predominantly regulated at posttranscriptional levels

The fluxes through glycolytic enzymes in Saccharomyces cerevisiae are predominantly regulated at posttranscriptional levels
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DOI:
10.1073/pnas.0707476104
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发表时间:
2007-10-02
影响因子:
11.1
通讯作者:
Bakker, Barbara M.
Bakker, Barbara M.
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Daran-Lapujade, Pascale;Rossell, Sergio;Bakker, Barbara M.

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代谢通量可以“分层”调节,例如,通过基因表达的变化调节酶的能力(V(max))和/或通过酶与底物、产物或变构效应物的“代谢”相互作用。在本研究中,开发了一种方法来剖析分层调节的转录,翻译,蛋白质降解和翻译后修饰的贡献。该方法应用于酵母在缺氧和苯甲酸消耗其ATIP的情况下,通过单个糖酵解酶对通量的调节。代谢调节在很大程度上促成了糖酵解酶通量的近10倍变化。这一贡献从50%到80%不等,取决于糖酵解步骤和所测试的培养条件。在50-20%的通量分级调节中,转录起次要作用,而蛋白质合成或降解的调节是最重要的。这些也贡献了75-100%的蛋白质水平调节。
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.