The Pasteur effect in rat jejunum and the influence of nematode infections.

1. The Pasteur effect was shown after 15 min but not after 30 min incubation of jejunal rings from normal rats. 2. During 15-30 min incubation, the rate of anaerobic lactate production decreased, while aerobic lactate production remained unchanged. Thus oxygen was necessary to maintain the functional integrity of the tissue during this period. 3. After infection with either Nematospiroides dubius or Nippostrongylus brasiliensis, the Pasteur effect could not usually be shown, mainly due to a reduced rate of anaerobic lactate production. 4. The possible relationship of the loss of the Pasteur effect to the immune response is discussed.     

Mathematical model for carbohydrate energy metabolism. Mechanism of the Pasteur effect

The simple mathematical model based on the stoichiometric structure of carbohydrate metabolism and the only allosteric regulation presented, i. e. activation of phosphofructokinase by AMP, was used to study the mechanism of the Pasteur effect, e. g. interrelationship of glycolysis, the Krebs cycle and H-transporting shuttles at varying rates of oxidative phosphorylation and ATPase load. It was shown that the mechanism of the Pasteur effect is based on the presence of two negative feed-back mechanisms in carbohydrate metabolism, namely by the level of ATP in glycolysis and by the level of mitochondrial NADH in the Krebs cycle and H-transporting shuttles. It was also shown that the value and sign of the Pasteur effect depend on the level of ATPase load. The role of this phenomenon in stabilization of ATP in the cell is discussed. The effects of changes in the allosteric properties of phosphofructokinase and low activity of H-transporting shuttles on the Pasteur effect was studied. It was shown that the low values of the pasteur effect in tumour tissues are mainly determined by an insufficient activity of oxidative phosphorylation.     

History of the Pasteur effect and its pathobiology

Summary Long before the mechanism of fermentation was understood,Pasteur discovered an important regulatory phenomenon of carbohydrate metabolism. He observed that yeast consumes more sugar anaerobically than aerobically. This so-called Pasteur effect has been subject of many controversies and an analysis of the development of the concepts has been presented. Among the key errors made in the early evaluations was to emphasize the control of end product formation rather than of hexose utilization.The Pasteur phenomenon as understood at present is a complex coordinated control mechanism which operates at several levels. The basic phenomenon is a competition between glycolysis and oxidative phosphorylation for the available ADP and inorganic phosphate. Superimposed are allosteric controls of hexokinase (glucose-6-phosphate) and of phosphofructokinase (ATP). However, in some cells glucose-6-phosphate is not an inhibitor of hexokinase and ATP levels do not change significantly during transition from aerobic to anaerobic conditions. It is therefore clear that other secondary allosteric effectors such as inorganic phosphate play a significant role. The major conclusion is that there are multiple and different control mechanisms participating in the Pasteur effect in different cells.A loss of control in tumor cells gives rise to a high aerobic glycolysis. The history and possible significance of this in malignancy is described.     

Glycolysis and respiration in yeasts. The Pasteur effect studied by mass spectrometry.

Simultaneous and continuous measurements of changes in CO2 and O2 concentrations in glucose-metabolizing yeast suspensions by mass spectrometry enabled a study of the Pasteur effect (aerobic inhibition of glycolysis) in Saccharomyces uvarum and Schizosaccharomyces pombe. A different control mechanism operates in Candida utilis to give a damped oscillation after the anaerobic-aerobic transition. The apparent Km values for respiration of the three yeasts were in the range 1.3-1.8 microM-O2. The apparent Km values for O2 of the Pasteur effect were 5 and 13 microM for catabolite-repressed and derepressed S. uvarum respectively and 7 microM for Sch. pombe. These results are discussed with respect to currently accepted mechanisms for the control of glycolysis.     

Role of phosphate in the regulation of the Pasteur effect in Saccharomyces cerevisiae

The occurrence of the Pasteur effect in Saccharomyces cerevisiae in several conditions has been examined. In these conditions measurements of a series of metabolites potentially involved in the regulation of the effect were performed. These included, among others, adenine nucleotides, citrate, fructose 2,6-bisphosphate and phosphate. Only phosphate changed in a consistent way, increasing in anaerobiosis when the Pasteur effect occurred. It is concluded that, with the available data, only phosphate may be considered as a regulator of the Pasteur effect in this microorganism.