Constraints in the Application of Control Analysis to the Study of Metabolism in Hepatocytes
In recent years it has been argued that quantitative methods are essential for providing new insights into the nature of the living state (Kacser, 1983). A number of mathematical approaches have evolved to meet these demands for quantitative methodologies (Heinrich & Rapoport, 1974; Savageau, 1976; Kacser & Burns, 1979), and of these, control analysis has perhaps attracted the greatest attention. Although its advent has been greeted enthusiastically by many theorists, who see it as an ideal way to quantify the regulatory role of the enzymes of a metabolic pathway, but this analytical method has not yet been widely embraced by experimentalists, because of the difficulties encountered in applying it to complex cellular systems. The work that we shall report in this chapter will illustrate some of these difficulties. The cell system we have used for our studies is the isolated hepatocyte preparation, and we shall present some representative examples from the many hundreds of experiments we have performed in this area.
KeywordsControl Analysis NADH Dehydrogenase Glycolytic Flux Lactate Accumulation Adenine Nucleotide Translocase
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