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Bioen 599 F, Autumn 2000 Bioengineering Principles of Physiology |
Lecture Material and Notes Week 4, Lecture 10: Structural
and kinetic modeling in metabolic networks Lecture theme and outline: In this lecture we show how computer modeling can be used to increase our insight into the functioning of metabolic reaction networks. We distinguish between structural models on the one hand, which only take into account the stoichiometry of the network (i.e. how the different reactions interconvert the substrates, intermediates, and products), and kinetic models, which include kinetic information for each reaction. · Metabolic stoichiometry and its analysis · The nullspace of the stoichiometric matrix · Elementary flux modes and flux analysis · Parameters and variables in metabolic systems · Kinetic modeling: time-dependent dynamics · Kinetic modeling: steady state and control analysis Software programs available Suggested reading: Papers and Reviews: three papers are distributed 1. Schuster, S., Dandekar, T., & Fell, D.A. (1999) Trends Biotechnol. 17, 53-60. 2. Schuster, S., Fell, D.A., & Dandekar, T. (2000) Nature Biotechnol. 18, 326-332. 3. Mendes, P. (1997) Trends Biochem. Sci. 22, 361-363. Two give additional background; #4 reports on one of the first scientific meetings where the biotechnology community and metabolic control community exchanged insights. 4. Mendes, P., & Kell, D.B. (1997) Trends Biotechnol. 15, 6-7.#5 gives a details analysis of glycolysis in a trypanosome in which there was good correspondence with in vitro enzyme activity and in vivo fluxes. A follow-up appeared in PNAS 97: 2087-2092 (2000) 5. Bakker, B.M., Michels, P.A.M., Opperdoes, F.R., & Westerhoff, H.V. (1997) J. Biol. Chem. 272, 3207-3215.
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Contact the instructor at: kushmeri@u.washington.edu
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