Quantitative modeling of triacylglycerol homeostasis in yeast - metabolic requirement for lipolysis to promote membrane lipid synthesis and cellular growth

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...

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Bibliographic Details
Published in:European journal of biochemistry 2008-11, Vol.275 (22), p.5552-5563
Main Authors: Zanghellini, Jürgen, Natter, Klaus, Jungreuthmayer, Christian, Thalhammer, Armin, Kurat, Christoph F, Gogg-Fassolter, Gabriela, Kohlwein, Sepp D, von Grünberg, Hans-Hennig
Format: Article
Language:English
Subjects:
Biochemistry
Cell Growth Processes
dynamic flux-balance analysis
Ethanol - metabolism
Fatty Acids - biosynthesis
Glucose - metabolism
Homeostasis
Kinetics
Lipid Metabolism
Lipids
Lipolysis - physiology
Membrane Lipids - biosynthesis
Metabolism
Models, Biological
Saccharomyces cerevisiae
Simulation
systems biology
Systems Biology - methods
triacylglycerol degradation
Triglycerides - metabolism
Yeast
Yeasts - metabolism
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Summary: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-logarithmic 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 increase in cell size, demonstrating the importance of lipolysis for supporting efficient growth initiation.
ISSN:1742-464X
0014-2956
1742-4658
1432-1033
DOI:10.1111/j.1742-4658.2008.06681.x