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Metabolic Channeling in Organized Enzyme Systems: Experiments and Models

1995; Elsevier BV; Linguagem: Inglês

10.1016/s1569-2558(08)60246-5

1875-5291

Pedro Mendes, Douglas B. Kell, G. Rickey Welch,

Ion channel regulation and function

The intracellular milieu is not a simple, homogeneous, aqueous state: protein concentration is high in eukaryotes, and even higher in prokaryotes and in organelles such as mitochondria, and membrane surfaces are clearly abundant. Evidence gathered with various techniques indicates that the cellular water does not have the same properties as water in dilute aqueous solutions. These findings support the view that classical enzymological studies may not provide sufficiently relevant information for generating a correct understanding of cellular physiology. Cellular organization exists at the molecular level: enzymes aggregate in clusters and in many cases this affects their catalytic activity. Consecutive enzymes in a number of metabolic pathways can channel their common intermediates without release to the “bulk” solution. This process can occur either via stable (static) multienzyme complexes or via short-lived (dynamic) enzyme--metabolite--enzyme complexes. Static complexes are found in anabolic pathways such as amino acid, nucleotide, and protein biosynthesis, where most of the intermediates have no other function or destination in the cell; dynamic complexes occur in amphibolic pathways where there are various flo--bifurcations. Channeling between dynamic complexes of enzymes is in some ways harder to demonstrate since the enzyme--enzyme complexes are not stable and are thus not isolatable. Theoretical developments, and simulations of existing metabolic channeling models, are not abundant. We review such studies and propose how modeling should evolve, the better to match the evolution of physiological experiments from in vitro to in situ to in vivo.