Top Down Metabolic Control Analysis

In the top down approach to metabolic control analysis, reactions are grouped together into a few large blocks connected by a small number of intermediates. Control is analysed by adding inhibitors or activators and work within single blocks and measuring intermediates and fluxes, or by adding new branches and measuring changes in flux. The approach is experimentally and conceptually simple, and provides a complete, but coarse description of control in complex metabolic systems that are not easily accessible using other approaches. This paper gives an overview of the method, its equations and their derivations. It discusses the ways the approach has been used in organelles and cells to identify the sites of action of effectors, to measure the distribution of control by blocks of reactions, and to measure regulation by effectors.