Spectroscopic Evidence of Metabolic Control: Rapid measurements of intracellular events afford new evidence on mechanisms for metabolic control

Abstract

The Pasteur and Crabtree effects demonstrate that changes at the beginning of the metabolic sequence for glucose metabolism give rise to effects at the end, and vice versa. We have presented here three additional responses of the ascites tumor cell suspensions, and presumably more will be uncovered. Each one of these responses is a manifestation of factors in the underlying mechanism that are in the nature of chemical feedback of a linear or nonlinear nature. The metabolic reactions are sufficiently complex that it is unlikely that any single component or step need control metabolism in different types of cells or under all conditions for a particular cell. However, it is due to a favorable circumstance that, in an appropriate type of cell and with the use of a direct intracellular indicator for changes in ADP concentration, we can state that the respiratory metabolism of the ascites tumor cell suspension, as freshly withdrawn from the mouse abdomen, is limited by the intracellular ADP concentration, and that this is why these cells show a predominance of glycolytic over respiratory activity. The response of the metabolism to small and large additions of glucose illustrates aspects of the metabolic mechanism which involve control of endogenous metabolism and compartmentalization of ATP formed in oxidative phosphorylation, the net result being a depression of the respiratory activity. The results of this approach emphasize the importance of chemical assays of localized portions of the living cell in its physiological state.