Unraveling the complexity of flux regulation: A new method demonstrated for nutrient starvation in Saccharomyces cerevisiae Export

@article{rossell2006, abstract = {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 (ii) 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 (i) changes in maximum enzyme activity (Vmax, called hierarchical regulation) and (ii) 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. 10.1073/pnas.0509831103}, author = {Rossell, Sergio and van der Weijden, Coen C. and Lindenbergh, Alexander and van Tuijl, Arjen and Francke, Christof and Bakker, Barbara M. and Westerhoff, Hans V.}, citeulike-article-id = {2403509}, citeulike-linkout-0 = {http://dx.doi.org/10.1073/pnas.0509831103}, citeulike-linkout-1 = {http://www.pnas.org/cgi/content/abstract/103/7/2166}, citeulike-linkout-2 = {http://view.ncbi.nlm.nih.gov/pubmed/16467155}, citeulike-linkout-3 = {http://www.hubmed.org/display.cgi?uids=16467155}, day = {14}, doi = {10.1073/pnas.0509831103}, journal = {Proceedings of the National Academy of Sciences}, keywords = {mdb-thesis, metabolic-control-analysis, regulation, transcription, translation}, month = {February}, number = {7}, pages = {2166--2171}, posted-at = {2009-02-03 10:24:49}, priority = {2}, title = {Unraveling the complexity of flux regulation: A new method demonstrated for nutrient starvation in \emph{Saccharomyces cerevisiae}}, url = {http://dx.doi.org/10.1073/pnas.0509831103}, volume = {103}, year = {2006} }

TY - JOUR ID - rossell2006 L3 - citeulike-article-id:2403509 N2 - 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 (ii) 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 (i) changes in maximum enzyme activity (Vmax, called hierarchical regulation) and (ii) 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. 10.1073/pnas.0509831103 IS - 7 JF - Proceedings of the National Academy of Sciences EP - 2171 TI - Unraveling the complexity of flux regulation: A new method demonstrated for nutrient starvation in \emph{Saccharomyces cerevisiae} VL - 103 SP - 2166 KW - mdb-thesis KW - metabolic-control-analysis KW - regulation KW - transcription KW - translation AU - Rossell, Sergio AU - van der Weijden, Coen AU - Lindenbergh, Alexander AU - van Tuijl, Arjen AU - Francke, Christof AU - Bakker, Barbara AU - Westerhoff, Hans PY - 2006/02/14/ UR - http://dx.doi.org/10.1073/pnas.0509831103 ER -