SOME COMPLEXITIES OF METABOLIC REGULATION

I have attempted to present a view of metabolic control mechanisms which de-emphasizes the idea that regulation of a metabooic pathway occurs at a single sensitive point. With lipogenesis as an example, I have indicated not only that control is possible at each step in the sequence but each step can be controlled in a variety of ways. Since many metabolites are found to have a large number of different roles, changes in concentration of a single metabolite will have a multitude of metabolic consequences. I have also pointed out that simple chemical interactions between metabolites make it very difficult to assess what change in concentration of an effective species occurs under a given set of conditions. When I related the maximum rates of enzymes of lipogenesis and the overall rate of tissue lipogenesis as well as the maximum rates each of the Krebs cycle enzymes and tissue respiration, it appeared that many steps may be rate-limiting so that control is, from this point of view as well, possible at several points. Before further progress can be made in understanding the basic features of metabolic control in animal cells, at least one important technical development must be made. It will be necessary to measure instantaneous substrate concentration in each compartment of the cell. Then the changes in concentration of a large number of possible effectors can be followed and related to the change in rate of a given metabolic path. It seems to me that one of the characteristics of animal metabolism is the high degree of complexity and its large number of interactions between the various substrates, effectors, and enzymes. It is probably these multiplicities of interactions that enables the tightness and stability of control typical of animal cells. © 1969.