Regulation of Energy Metabolism in Hepatocytes

Control analysis has been applied experimentally to many pathways (Fell, 1992). However, the effort required to measure the elasticity, control and response coefficients makes a full empirical analysis unrealistic in all but rather simple systems. Consequently, most investigations have considered single enzymes or pathways, ignoring interactions with other cellular pathways. The most experimentally accessible way to measure regulation in complex systems like whole cells is to group reactions together into much larger blocks. The control and regulation of a simplified network of blocks that includes all the reactions in the cell can then be analysed. This is known as the top-down (Brand, 1996) or modular (Schuster et al., 1993) approach to control analysis. Top-down approaches have been used either to analyse the reactions in whole cells or organs around a single intermediate (Brand, 1996; Soboll et al., 1998) or to analyse a limited number of reactions around several intermediates (Groen et al., 1982; Kashiwaya et al., 1994). There has been no analysis of the grouped reactions of a whole cell with multiple intermediates. Such an analysis is necessary if we are to quantify and understand the importance of interactions between different major pathways in the cell, because it is only when we include all of the reactions that the full complexity appears. A great strength of control analysis is that it provides the methodology and language to describe this complexity meaningfully.