A Control Analysis of Metabolic Regulation
Why is it that many of the classical ideas of metabolic regulation have been so difficult to reconcile with metabolic control analysis? A major reason seems to be a difference in the questions asked by the two approaches. Analysis of metabolic control asks how changes in parameters affect variables1,2 (for recent review see Ref. 3). Analysis of metabolic regulation asks how changes in metabolite concentrations or functions of metabolite concentrations affect variables4. Although at first sight there seems to be little difference between these questions, deeper study shows that there is an important difference. From a systems point of view parameters are constant quantities, and some metabolites that act as regulators, e.g. hormones, are often parameters of metabolic systems. Nevertheless, many of the metabolites classically regarded as regulators are themselves variables, so that the question of metabolic regulation often concerns the effect of one variable on another, e.g., of the concentration of a feedback inhibitor on the flux through its pool. The latter type of question has up to now been avoided in control analysis; here we will show how it can be answered.
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