Biochemical systems theory

Although the importance of a systemic perspective on metabolism has only recently attained widespread attention, a formal frameworks for systemic analysis has already been developed since the late 1960s. Biochemical Systems Theory (BST), put forward by Savageau and others [142, 144 147], seeks to provide a unified framework for the analysis of cellular reaction networks. Predating Metabolic Control Analysis, BST emphasizes three main aspects in the analysis of metabolism [319] (i) the importance of the interconnections, rather than the components, for cellular function (ii) the nonlinearity of biochemical rate equations (iii) the need for a unified mathematical treatment. Similar to MCA, the achievements associated with BST would warrant a more elaborate treatment, here we will focus on BST solely as a tool for the approximation and numerical simulation of complex biochemical reaction networks. 

M. A. Savageau, Biochemical systems theory and metabolic control theory 1. Fundamental similarities and differences. Math. Biosci. 86, 127 145 (1987). 

T. C. Ni and M. A. Savageau, Application of biochemical systems theory to metabolism in human red blood cells. Signal propagation and accuracy of representation. J. Biol. Chem. 271... 

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]. 

Savageau, M. A. (1991b). Biochemical systems theory operational differences among variant representations and their significance. J. Theoret. Biol. 151, 509-530. 

Sorribas, A. Savageau, M. A. (1989a). A comparison ofvariant theories of intact biochemical systems 1 Enzyme-enzyme interactions and biochemical systems theory. Math. Biosci. 94, 161-193. Sorribas, A. Savageau, M. A. (1989b). A comparison of variant theories of intact biochemical systems 2 Flux oriented and metabolic control theaies. Math. Biosci. 94,195-238. 

Sorribas, A. Savageau, M. A, (1989c). Strategies for representing metabolic pathways within biochemical systems theory reversible pathways. Math. Biosci. 94,239-269. 

D. Biochemical Systems Theory and Nutrient-Response Analysis of Data on Three Dietary Proteins Conclusions... 

The object of metabolic control theory is to provide a sound mathematical foundation for the quantitative estimation of the role played by individual enzymes on the control of flux through a metabolic pathway and also the control exerted by individual enzymes on the concentration of intermediate metabolites in the pathway. The general principles of metabolic control theory and biochemical systems theory can be visualized by considering the simple metabolic pathway in Fig. 6. The numbers above the arrows... 

Metabolic control analysis Kinetic modeling Biochemical systems theory Cybernetic modeling... 

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