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 o f intermediates. Control is analysed by adding inhibitors or activator s that work within single blocks and measuring intermediates and fluxe s, or by adding new branches and measuring changes in flux. The approa ch is experimentally and conceptually simple, and provides a complete but coarse description of control in complex metabolic systems that ar e not easily accessible using other approaches. This paper gives an ov erview of the method, its equations and their derivations. It discusse s the ways the approach has been used in organelles and cells to ident ify the sites of action of effecters, to measure the distribution of c ontrol by blocks of reactions, and to measure regulation by effecters. (C) 1996 Academic Press Limited.