9. COMPARATIVE BIOCHEMISTRY OF GLYCOLYSIS
415
Rapid regeneration of ATP, and thus a possible deficiency in ADP, may
occur also through oxidative phosphorylations (see Section II, C).
From the foregoing, it is evident that the maintenance of a proper
balance between the concentrations of ATP and of ADP must be of
considerable importance in determining the rate of glycolysis in the
intact cell.
C. THE PASTEUR EFFECT
In a great variety of cells, glycolysis is reduced in the presence of
air. The mechanisms involved in this inhibition of carbohydrate utilization by oxygen, first described by Pasteur, have proved extremely elusive to experimental analysis (30, 31).
Since lactic acid, produced during glycolysis, can be resynthesized
to glycogen or to glucose by the use of oxidative energy, respiration may
produce an apparent decrease in carbohydrate utilization. Therefore, although aerobiosis may not decrease glycolysis necessarily, more carbohydrate would be present in the cell under aerobic than under anaerobic
conditions. (32). Probably other factors play a more important role in
producing the Pasteur effect.
Aerobic metabolism may result in a deficiency of ADP and (or) of
inorganic phosphate. Oxidative phosphorylations generate the formation
of ATP from ADP and inorganic phosphate. If the latter were in limited
supply, glycolysis would be inhibited because of the required participation of inorganic phosphate in the oxidation of glyceraldehyde-3-phosphate to 2,3-diphosphoglycerate (Reaction 6). It has been pointed out
above (Section II, B) that glycolysis can be inhibited because of a
deficiency of ADP as a phosphate acceptor from 2,3-diphosphoglycerate
(Reaction 7) and from phosphopyruvate (Reaction 10). The possibility of such a mechanism is indicated by the observations that compounds which uncouple oxidative phosphorylations (e.g., dinitrophenol)
and thereby increase the availability of inorganic phosphate and of
ADP, reduce or even abolish the Pasteur effect (33-36). Furthermore,
addition of mitochondria to a reconstructed system consisting of purified enzymes and coenzymes of glycolysis results in a marked reduction
of glucose uptake and of lactic acid formation. This is associated with a
decrease in ADP and in inorganic phosphate (37, 38). Therefore, competition between mitochondrial and glycolytic enzymes for limiting
amounts of ADP and of inorganic phosphate can result in an inhibition
of glycolysis.
On the other hand, using brain extracts as a source of glycolytic
enzymes, Aisenberg et dl. (39) have reported that inhibition of glycolysis by mitochondria is not associated with a depletion of ADP or of
415
Rapid regeneration of ATP, and thus a possible deficiency in ADP, may
occur also through oxidative phosphorylations (see Section II, C).
From the foregoing, it is evident that the maintenance of a proper
balance between the concentrations of ATP and of ADP must be of
considerable importance in determining the rate of glycolysis in the
intact cell.
C. THE PASTEUR EFFECT
In a great variety of cells, glycolysis is reduced in the presence of
air. The mechanisms involved in this inhibition of carbohydrate utilization by oxygen, first described by Pasteur, have proved extremely elusive to experimental analysis (30, 31).
Since lactic acid, produced during glycolysis, can be resynthesized
to glycogen or to glucose by the use of oxidative energy, respiration may
produce an apparent decrease in carbohydrate utilization. Therefore, although aerobiosis may not decrease glycolysis necessarily, more carbohydrate would be present in the cell under aerobic than under anaerobic
conditions. (32). Probably other factors play a more important role in
producing the Pasteur effect.
Aerobic metabolism may result in a deficiency of ADP and (or) of
inorganic phosphate. Oxidative phosphorylations generate the formation
of ATP from ADP and inorganic phosphate. If the latter were in limited
supply, glycolysis would be inhibited because of the required participation of inorganic phosphate in the oxidation of glyceraldehyde-3-phosphate to 2,3-diphosphoglycerate (Reaction 6). It has been pointed out
above (Section II, B) that glycolysis can be inhibited because of a
deficiency of ADP as a phosphate acceptor from 2,3-diphosphoglycerate
(Reaction 7) and from phosphopyruvate (Reaction 10). The possibility of such a mechanism is indicated by the observations that compounds which uncouple oxidative phosphorylations (e.g., dinitrophenol)
and thereby increase the availability of inorganic phosphate and of
ADP, reduce or even abolish the Pasteur effect (33-36). Furthermore,
addition of mitochondria to a reconstructed system consisting of purified enzymes and coenzymes of glycolysis results in a marked reduction
of glucose uptake and of lactic acid formation. This is associated with a
decrease in ADP and in inorganic phosphate (37, 38). Therefore, competition between mitochondrial and glycolytic enzymes for limiting
amounts of ADP and of inorganic phosphate can result in an inhibition
of glycolysis.
On the other hand, using brain extracts as a source of glycolytic
enzymes, Aisenberg et dl. (39) have reported that inhibition of glycolysis by mitochondria is not associated with a depletion of ADP or of