Analysis of Metabolic Control:- The Control Coefficient Quantifies the Effect of a Change in Enzyme Activity on Metabolite Flux through a Pathway
Quantitative data obtained as described in Figure 15–33 can be used to calculate a flux control coefficient, C, for each enzyme in a pathway. This coefficient ex presses the relative contribution of each enzyme to set ting the rate at which metabolites flow through the pathway—that is, the flux, J. C can have any value from 0.0 (for an enzyme with no impact on the flux) to 1.0 (for an enzyme that wholly determines the flux). An en zyme can also have a negative flux control coefficient. In a branched pathway, an enzyme in one branch, by drawing intermediates away from the other branch, can have a negative impact on the flux through that other branch (Fig. 15–34). C is not a constant, and it is not intrinsic to a single enzyme; it is a function of the whole system of enzymes, and its value depends on the concentrations of substrates and effectors. When real data from the experiment on glycolysis in a rat liver extract (Fig. 15–33) were subjected to this kind of analysis, investigators found flux control coefficients (for enzymes at the concentrations found in the extract) of 0.79 for hexokinase, 0.21 for PFK-1, and 0.0 for phosphohexose isomerase. It is not just fortuitous that these values add up to 1.0; we can show that for any complete pathway, the sum of the flux control coefficients must equal unity.
FIGURE 15–34 Flux control coefficient, C, in a branched metabolic pathway. In this simple pathway, the intermediate B has two alternative fates. To the extent that reaction B → E draws B away from the pathway A → D, it controls that pathway, which will result in a negative flux control coefficient for the enzyme that catalyzes step B → E. Note that the sum of all four coefficients equals 1.0, as it must.
