Regulatory Mechanisms in Carbohydrate Metabolism

The inhibition of glycolysis by respiration (Pasteur effect) and the inhibition of respiration by glycolysis (Crabtree effect) represent nonhormonal regulatory mechanisms of cellular metabolism. Some of the previous work on these phenomena in intact cells will be reviewed in subsequent papers (1, 2) together with a report on recent experimental work on ascites tumor cells. The difficulty of obtaining broken cell preparations which exhibit a Pasteur effect has led to the view that this phenomenon is dependent to some degree on the structural integrity of the tissue. However, in 1950, Meyerhof and Fiala (3) demonstrated a Pasteur effect in sonically disrupted yeast. The slight inhibition of glycolysis observed under aerobic conditions was released upon addition of an uncoupler of oxidative phosphorylation such as p-nitrophenol. Terner (4, 5) demonstrated, in homogenates of rat or guinea pig mammary gland, a Pasteur effect which was released by p-nitrophenol or by high concentrations of adenosine 5-phosphate. Aisenberg, Reinafarje and Potter1 reported on a Pasteur effect in a cell-free system consisting of a glycolyxing brain extract and respiring rat liver mitochondria (6, 7). Interactions between lactic dehydrogenase, pyruvate kinase and mitochondria were studied by Von Korff and Twedt (8). Observations on a reconstructed system of glycolysis and respiring mitochondria exhibiting a Pasteur effect and a Crabtree effect were reported from this laboratory (9, 10). Many theories have been proposed for the mechanism of the Pasteur effect (cJ 11, 12). In recent years, however, a number of ‘investigators (13-18) have emphasized the importance of the intracellular levels of inorganic phosphate and adenine nucleotides in the regulation of glycolysis and oxidative phosphorylation. It was proposed that the Pasteur and Crabtree effects may be due to a competition between the oxidative phosphorylation and glycolytic systems for cofactors such as inorganic phosphate and adenine nucleotides. In order to explore the kinetic aspects of such a competition and the effect of the concentration of enzymes and coenzymes, a reconstructed system was devised. This system was composed