Global metabolic changes following loss of a feedback loop reveal dynamic steady states of the yeast metabolome.

@article{citeulike:937429, abstract = {Metabolic enzymes control cellular metabolite concentrations dynamically in response to changing environmental and intracellular conditions. Such real-time feedback regulation suggests the global metabolome may sample distinct dynamic steady states, forming "basins of stability" in the energy landscape of possible metabolite concentrations and enzymatic activities. Using metabolite, protein and transcriptional profiling, we characterize three dynamic steady states of the yeast metabolome that form by perturbing synthesis of the universal methyl donor S-adenosylmethionine (AdoMet). Conversion between these states is driven by replacement of serine with glycine+formate in the media, loss of feedback inhibition control by the metabolic enzyme Met13, or both. The latter causes hyperaccumulation of methionine and AdoMet, and dramatic global compensatory changes in the metabolome, including differences in amino acid and sugar metabolism, and possibly in the global nitrogen balance, ultimately leading to a G1/S phase cell cycle delay. Global metabolic changes are not necessarily accompanied by global transcriptional changes, and metabolite-controlled post-transcriptional regulation of metabolic enzymes is clearly evident.}, address = {Center for Systems and Synthetic Biology, University of Texas, 1 University Station, A4800, Austin, TX 78712-0159, USA; Institute for Cellular and Molecular Biology, University of Texas, 1 University Station, A4800, Austin, TX 78712-0159, USA.}, author = {Lu, Peng and Rangan, Anupama and Chan, Sherwin Y. Y. and Appling, Dean R. R. and Hoffman, David W. W. and Marcotte, Edward M. M. }, citeulike-article-id = {937429}, doi = {10.1016/j.ymben.2006.06.003}, issn = {1096-7176}, journal = {Metab Eng}, keywords = {allostery, regulation}, month = {June}, number = {1}, pages = {8--20}, posted-at = {2007-08-09 06:35:01}, priority = {5}, title = {Global metabolic changes following loss of a feedback loop reveal dynamic steady states of the yeast metabolome.}, url = {http://dx.doi.org/10.1016/j.ymben.2006.06.003}, volume = {9}, year = {2006} }

TY - JOUR ID - citeulike:937429 L3 - citeulike-article-id:937429 TI - Global metabolic changes following loss of a feedback loop reveal dynamic steady states of the yeast metabolome. JF - Metab Eng VL - 9 IS - 1 SP - 8 EP - 20 AD - Center for Systems and Synthetic Biology, University of Texas, 1 University Station, A4800, Austin, TX 78712-0159, USA; Institute for Cellular and Molecular Biology, University of Texas, 1 University Station, A4800, Austin, TX 78712-0159, USA. SN - 1096-7176 N2 - Metabolic enzymes control cellular metabolite concentrations dynamically in response to changing environmental and intracellular conditions. Such real-time feedback regulation suggests the global metabolome may sample distinct dynamic steady states, forming "basins of stability" in the energy landscape of possible metabolite concentrations and enzymatic activities. Using metabolite, protein and transcriptional profiling, we characterize three dynamic steady states of the yeast metabolome that form by perturbing synthesis of the universal methyl donor S-adenosylmethionine (AdoMet). Conversion between these states is driven by replacement of serine with glycine+formate in the media, loss of feedback inhibition control by the metabolic enzyme Met13, or both. The latter causes hyperaccumulation of methionine and AdoMet, and dramatic global compensatory changes in the metabolome, including differences in amino acid and sugar metabolism, and possibly in the global nitrogen balance, ultimately leading to a G1/S phase cell cycle delay. Global metabolic changes are not necessarily accompanied by global transcriptional changes, and metabolite-controlled post-transcriptional regulation of metabolic enzymes is clearly evident. KW - allostery KW - regulation AU - Lu, Peng AU - Rangan, Anupama AU - Chan, Sherwin AU - Appling, Dean AU - Hoffman, David AU - Marcotte, Edward PY - 2006/06/30/ UR - http://dx.doi.org/10.1016/j.ymben.2006.06.003 ER -