Systems biology metabolic modeling

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Levering, J., Musters, M.W.J.M., Bekker, M., et al. (2012) Role of phosphate in the central metabolism of two lactic acid bacteria - a comparative systems biology approach Modelling glycolysis of lactic add bacteria. FEBS J 279, 1274-1290. 

Bugrim A, Nikolskaya T, Nikolsky Y. Early prediction of drug metabolism and toxicity systems biology approach and modeling. Drug Discov Today 2004 9 127-35. 

Nonetheless, the construction of explicit kinetic models allows a detailed and quantitative interrogation of the alleged properties of a metabolic network, making their construction an indispensable tool of Systems Biology. The translation of metabolic networks into ordinary differential equations, including the experimental accessibility of kinetic parameters, is one of the main aspects of this contribution and is described in Section III. 

Bottom-up systems biology does not rely that heavily on Omics. It predates top-down systems biology and it developed out of the endeavors associated with the construction of the first mathematical models of metabolism in the 1960s [10, 11], the development of enzyme kinetics [12-15], metabolic control analysis [16, 17], biochemical systems theory [18], nonequilibrium thermodynamics [6, 19, 20], and the pioneering work on emergent aspects of networks by researchers such as Jacob, Monod, and Koshland [21-23]. 

These two complementary systems allow the bacterial cell to metabolize lactose in response to two stimuli. Switching on the expression of the lac operon requires both the absence of glucose and the presence of lactose. This series of switches allows complex expression patterns to be built up from simple components. For this reason, the lac system is a model for other, apparently more complex, biological control systems, such as hormone action or embryonic development. 

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