In this article we will discuss about the inhibition of glycolysis by oxygen.
Some controls, particularly hormonal, are carried out on glycolysis. We will examine here only the effect of oxygen known as the Pasteur effect because Pasteur was the first scientist to observe that in yeast, glucose was less rapidly consumed in aerobiosis than in anaerobiosis.
In other words, the introduction of oxygen brings about a decrease of the rate of glycolysis. The advantage of this phenomenon is obvious when one examines the energy balances as was just done above, and when one knows the high energy’ balance of aerobic oxidation to CO2 + H2O: since in aerobiosis a much greater number of molecules of ATP are formed per molecule of glucose, the cells need use less glucose to meet their energy requirements. While the advantages of the Pasteur effect are obvious, the mechanisms involved are far from clear.
We will now review some of the existing hypotheses:
1) First of all, it is possible — in some cases at least — that the phenomenon is more apparent than real, because in presence of oxygen, a very large proportion of lactic acid formed can be reconverted into glucose (as mentioned above), which decreases consumption of glucose.
2) An allosteiic regulation takes place at the level of phosphofructokinase. This enzyme is activated by AMP and Pi (available in anaerobiosis) and inhibited by ATP (formed in aerobiosis at the cost of ADP and Pi).
If one considers that the ultimate objective of glycolysis followed by the Krebs cycle is the production of ATP, and that phosphofructokinase is the first enzyme of this metabolic pathway (which is justified because the previous enzyme, phosphohexo-isomerase does not act solely in glycolysis), it may be said that inhibition of phosphofructokinase by ATP is a case of feedback inhibition, where the first enzyme of the metabolic pathway is inhibited by the final product.
In reality, the phenomena are even more complex, because one must take into consideration the inhibiting effect — on phosphofructokinase – of citric acid which can also be considered as a final product of glycolysis, because — as will be seen in the following — it is formed at the beginning of the Krebs cycle.
Furthermore, fructose-1, 6-bisphosphatase (enzyme acting like phosphofructokinase, but in the direction of neoglucogenesis) is on the contrary inhibited by AMP. Thus, in anaerobiosis, the increase in AMP concentration has an activating effect on glycolysis and an inhibiting effect on neoglucogenesis whereas in aerobiosis the increase in ATP concentration inhibits glycolysis and favours neoglucogenesis.
It appears that the regulation of enzymatic activity, especially in the case of phosphofructokinase, is the most important factor of the control of glycolysis. However, in order to show the complexity of this problem, we will mention 3 more hypotheses which have been advanced.
3) In aerobiosis, ADP and Pi are utilized to form ATP during the oxidation of pyruvate to CO2 + H2O). But, these three reactions of glycolysis — those catalyzed by glyceraldehyde-3-℗-dehydrogenase, phosphoglycerate kinase and pyruvate kinase — have precisely Pi or ADP as substrate.
It was therefore suggested that there is a possibility of a competition, for ADP and Pi between respiration (i.e. the mitochondrial oxidations-reductions) and glycolysis, although these 2 processes take place in different cellular compartments.
4) Some enzymes of glycolysis, particularly glyceraldehyde-3-℗- dehydrogenase, the acting mechanism of which has been explained in some more details, contain — SH groups required for catalytic activity. An oxidation of these groups in aerobiosis would cause an inhibition of glycolysis.
5) Glucose-6-℗ can — instead of entering the pathway of glycolysis — be oxidized to 6-phosphogluconic acid (the pathway of pentose-phosphates, see fig. 4-39); this oxidation favoured in aerobiosis, would tend to divert a part of glucose from glycolysis.
It is possible that several of these mechanisms contribute to the Pasteur effect. There exists a reverse phenomenon: in presence of high glucose concentrations, cellular respiration is inhibited: this is the Crabtree effect.