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Bioen 599 F, Autumn 2000 Bioengineering Principles of Physiology |
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Lecture Material and Notes Week 4, Lecture 11: Analysis
of control and regulation in metabolic networks Lecture theme and outline: In this lecture we explore a framework for studying the control and regulation of metabolic networks in a quantitative way. The power of this framework is that it allows us to understand what happens on the level of the whole system in terms of the kinetic and thermodynamic properties of the individual enzyme catalyzed reactions that constitute the system. · A general definition of metabolic regulation · Metabolic function at the systems level · Metabolism as a system of coupled supply and demand blocks · Rate characteristics of supply and demand - the steady state · Quantifying control of flux and concentration - control coefficients · Relating control to the properties of the supply and demand - elasticity coefficients · Dissecting elasticity coefficients - kinetic and thermodynamic contributions · Putting it all together - the regulatory designs of the Stellenbosch organism and of a typical ATP-ADP couple Papers and Reviews: The first reading reprints the basic and classic work by Kacser and Burns with comments on advances made in the ensuing 21 years. It details the original developments of the ideas presented in the lecture 1. Kacser, H., Burns, J.A. and Fell, D.A. (1995) The control of flux: 21 years on. Biochem. Soc. Trans. 23, 341-366. (http://www.sun.ac.za/biochem/KBF95.pdf) The second is an up to date outline and summary of the principles involved. 2. Hofmeyr, J.-H.S. and Cornish-Bowden, A. (2000) Regulating the cellular economy of supply and demand. FEBS Lett. 476, 47-51. (http://www.sun.ac.za/biochem/FEBS_23792.pdf) The third paper analyses yeast as a supply-demand problem, shows that ethanol production is only increased by increasing the ATPase flux, and is a paradigm for thinking about mammalian systems including muscle: 3. Hofmeyr, J.-H.S. (1997) Anaerobic energy metabolism in yeast as a supply-demand system. In New Beer in an Old Bottle: Eduard Buchner and the Growth of Biochemical Knowledge (Cornish-Bowden, A., ed) pp. 225-242. Universitat de València, Valencia. (http://www.sun.ac.za/biochem/buchner.pdf) The other papers give additional background and examples: 4. Hofmeyr, J.-H.S. and Cornish-Bowden, A. (1991) Quantitative assessment of regulation in metabolic systems. Eur. J. Biochem. 200, 223-236. 5. Hofmeyr, J.-H.S. (1995) Metabolic regulation: a control-analytic perspective. J. Bioenerg. Biomembranes 27, 479-490. (http://www.sun.ac.za/biochem/JBB95.pdf)
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Contact the instructor at: kushmeri@u.washington.edu
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