The cell-bag of enzymes or network of channels?

Everyone who has taken a biochemistry course since 1950 has been told during the course, "The cell is not a bag of enzymes." To the extent that our teachers explained this statement, it meant that, even though most enzymes are soluble proteins, the cytoplasm is not simply a highly concentrated protein solution bathing a set of organelles. Investigations of membranous enzyme assemblies, such as the respiratory chain, and of tightly bound complexes, such as pyruvate dehydrogenase, have shown some advantages that flow from juxtaposition of enzymes catalyzing sequential reactions, e.g., efficient catalysis of multistep sequences, rapid metabolic adjustments to environmental changes within a cell, efficient regulation of metabolic pathways, and so forth. If the cell is not a bag of enzymes, what is it? New experimental approaches in the past decade have suggested a high degree of organized structure within regions of cells that do not readily reveal such organization when viewed by conventional techniques, such as electron microscopy. Evidently, protein-protein interactions play large roles in stabilizing such structures (7), a concept flowing naturally from several observations about protein biology and biochemistry. First, intracellular protein concentrations are far higher (up to 350 mg/ml) than the concentrations at which enzymes are usually studied, for example, in assays of enzyme activity. Weak protein associations that might maintain organized intracellular structures could well disappear at the far lower protein concentrations with which enzyme kineticists work in vitro. Second, evolution seems to have conserved not only functional sites of protein molecules but also structural features that might determine the abilities of proteins to associate with one another. McConkey (13) showed that two-dimensional gel electrophoresis of human and hamster proteins reveals at least 50% congruence between the two patterns, as if molecular size and surface distribution of charged amino acid residues had been retained across the evolutionary gulf separating these species. Third, molar concentrations of many enzymes in vivo are quite high. Srivastava and Bernhard (20) assembled data indicating that in rabbit muscle cells, concentrations of the glycolytic enzymes are higher than the intracellular concentrations of the substrates for those enzymes. This suggested that at any instant most of the intracellular content of a particular intermediate is enzyme bound and is perhaps undergoing direct transfer from one enzyme to the next. Indeed, Ovaidi (14) has suggested that intracellular enzyme complexes are stabilized by "dynamic" interactions, in which two enzymes are bound by their joint affinity for an intermediate that is being transferred from one enzyme to the next in a metabolic