Unraveling the complexity of flux regulation:: A new method demonstrated for nutrient starvation in Saccharomyces cerevisiae
Unraveling the complexity of flux regulation:: A new method demonstrated for nutrient starvation in Saccharomyces cerevisiae
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DOI：
10.1073/pnas.0509831103
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发表时间：
2006-02-14
影响因子：
11.1
通讯作者：
Westerhoff, HV
中科院分区：
文献类型：
--
作者：
Rossell, S;van der Weijden, CC;Westerhoff, HV
一个重要的问题是代谢通量在多大程度上受基因表达或代谢调节的调节。这个问题有两个不同的方面：（i）通过途径中的各个步骤的通量的局部调节和（h）这种局部调节对途径通量的影响。我们开发了监管分析，以解决前一方面的所有步骤的途径。我们展示了酿酒酵母如何通过其个别糖酵解和发酵酶调节通量的问题时，面临营养饥饿的方法。调节被定量地分解为（J）最大酶活性（V-max，称为分级调节）的变化和（h）酶与代谢的其余部分的相互作用的变化（称为代谢调节）。在一个单一的途径，通过各个步骤的流量的调节从完全分层到完全代谢。现有的范式的流量调节（如单和多位点调制和专门的代谢调节）进行了测试的一个完整的途径和伪造的一个重要的模式生物的主要途径。我们提出了一种更微妙的通量调节机制，不同的酶具有不同的作用，即，“领导.....追随者”或“保守派”，后者试图阻止通量的变化。这项研究使得这种微妙的，所以典型的生物系统，易于实验，并邀请有关的驱动器和制约因素的问题重新制定代谢通量调节。
An important question is to what extent metabolic fluxes are regulated by gene expression or by metabolic regulation. There are two distinct aspects to this question: (i) the local regulation of the fluxes through the individual steps in the pathway and (h) the influence of such local regulation on the pathway's flux. We developed regulation analysis so as to address the former aspect for all steps in a pathway. We demonstrate the method for the issue of how Saccharomyces cerevisiae regulates the fluxes through its individual glycolytic and fermentative enzymes when confronted with nutrient starvation. Regulation was dissected quantitatively into (J) changes in maximum enzyme activity (V-max, called hierarchical regulation) and (h) changes in the interaction of the enzyme with the rest of metabolism (called metabolic regulation). Within a single pathway, the regulation of the fluxes through individual steps varied from fully hierarchical to exclusively metabolic. Existing paradigms of flux regulation (such as single- and multisite modulation and exclusively metabolic regulation) were tested for a complete pathway and falsified for a major pathway in an important model organism. We propose a subtler mechanism of flux regulation, with different roles for different enzymes, i.e., "leader.....follower," or "conservative," the latter attempting to hold back the change in flux. This study makes this subtlety, so typical for biological systems, tractable experimentally and invites reformulation of the questions concerning the drives and constraints governing metabolic flux regulation.