tailieunhanh - Báo cáo khoa học: Quantitative modeling of triacylglycerol homeostasis in yeast – metabolic requirement for lipolysis to promote membrane lipid synthesis and cellular growth

Triacylglycerol metabolism inSaccharomyces cerevisiae was analyzed quan-titatively using a systems biological approach. Cellular growth, glucose uptake and ethanol secretion were measured as a function of time and used as input for a dynamic flux-balance model. | ễFEBS Journal Quantitative modeling of triacylglycerol homeostasis in yeast - metabolic requirement for lipolysis to promote membrane lipid synthesis and cellular growth Jurgen Zanghellini1 Klaus Natter2 Christian Jungreuthmayer3 Armin Thalhammer1 Christoph F. Kurat2 Gabriela Gogg-Fassolter2 Sepp D. Kohlwein2 and Hans-Hennig von Grunberg1 1 Institute of Chemistry University of Graz Austria 2 Institute of Molecular Biosciences University of Graz Austria 3 Trinity Center of Bioengineering Trinity College Dublin Ireland Keywords dynamic flux-balance analysis lipid metabolism Saccharomyces cerevisiae systems biology triacylglyceroldegradation Correspondence J. Zanghellini Institute of Chemistry University of Graz HeinrichstraBe 28 A-8010 Graz Austria Fax 43 316 380 9850 Tel 43 316 380 5421 E-mail These authors contributed equally to this work Received 11 July 2008 revised 5 September 2008 accepted 9 September 2008 Triacylglycerol metabolism in Saccharomyces cerevisiae was analyzed quantitatively using a systems biological approach. Cellular growth glucose uptake and ethanol secretion were measured as a function of time and used as input for a dynamic flux-balance model. By combining dynamic mass balances for key metabolites with a detailed steady-state analysis we trained a model network and simulated the time-dependent degradation of cellular triacylglycerol and its interaction with fatty acid and membrane lipid synthesis. This approach described precisely both qualitatively and quantitatively the time evolution of various key metabolites in a consistent and self-contained manner and the predictions were found to be in excellent agreement with experimental data. We showed that during pre-loga-rithmic growth lipolysis of triacylglycerol allows for the rapid synthesis of membrane lipids whereas de novo fatty acid synthesis plays only a minor role during this growth phase. Progress in triacylglycerol hydrolysis directly correlates with an