Metabolic control analysis 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. 

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]. 

Metabolic control analysis (MCA) is a specialized theory that is concerned with particular sensitivity coefficients, elasticity coefficients and control coefficients. These coefficients tell us how a steady state of a biochemical system shifts in response to perturbation in enzyme activities or external (clamped) substrate concentration [53, 209],... 

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

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