Experimental Analysis of Spatiotemporal Organization of Metabolism in Intact Cells: The Enigma of “Metabolic Channeling” and “Metabolic Compartmentation”

Abstract

The organization and control of multienzyme systems in the living cell raises numerous challenging questions. Based on studies of proteinprotein interactions in multienzyme aggregates (Frieden and Nichol, 1981; Welch, 1977) and permeabilized cells (Shannon et al., 1977), several conclusions can be drawn concerning the intracellular behavior of complex metabolic pathways. One of the interesting concepts evolving from such studies is that of “channeling”, i.e. a substrate is channeled between two or more enzymes while it is diffusionally constrained from the bulk phase. Together with hypotheses of “channeling”, “metabolic compartmentation” and interactions of enzymes with cytoskeletal components, there are also differing views as to allosteric controls of multienzyme pathway a Thus, a cell viewed as a multienzyme system represents a complex structure in which the net activity of one enzyme is affected by that of all the enzymes in the system. According to Kacser and Burns (1979), detailed, or even complete, knowledge of an enzyme or all the enzymes in isolation is, therefore, insufficient to determine the role they play when they are embedded in the cell matrix and linked kinetically to each other.