60 A SYMPOSIUM ON RESPIRATORY ENZYMES 



with the Pasteur effect through work done by Ostern and Mann (29). 

 They found that the addition of adenosine triphosphate (ATP) to 

 mashed muscle depressed aerobic glycolysis and raised the Meyer- 

 hof Quotient from 2.2 to 4. Later Lennerstrand (30) discussed the 

 possibility that with aerobic over-phosphorylation of adenylic acid 

 (Ad), the ratio ATP: Ad might become too high to permit adenylic 

 acid to function effectively as a transmitter in fermentation. 



A scheme based on the recent development of the biochemistry of 

 phosphate turnover has been presented and discussed in detail else- 

 where (3). Figure 3 is taken from this paper. The upper cycle, re- 

 volving clockwise, represents anaerobic glycolysis; the lower cycle, 

 revolving counter-clockwise, represents aerobic resynthesis. It ap- 

 pears that the clockwise run of the glycolytic cycle depends on the 

 outflow of the energy-rich phosphate created in the reaction. An 

 actual reversal of the cycle back to the aldehyde stage may occur 

 when through the aerobic influx of new energy-rich phosphate 

 the carboxyl-bound phosphate in 1,3-diphosphoglyceric acid (Ph- 

 glyceryl-Ph) cannot be removed. 



In the Meyerhof-Warburg equilibrium reaction, as the diagram 

 shows, inorganic phosphate is bound when the reaction proceeds to 

 the right and is set free when it proceeds to the left. Therefore in- 

 organic phosphate concentration can become a rate-determining 

 factor. Meyerhof et al. (31) and Belitzer (32) have pointed out that 

 in muscle the increased concentration of inorganic phosphate 

 through creatinephosphate breakdown should be regarded as the 

 cause of the release of metabolic activity due to stimulation. Along 

 similar lines, Johnson (33) recently suggested that the lowering of 

 inorganic phosphate concentration might be a possible cause of 

 aerobic inhibition of glycolysis. Inorganic phosphate concentration 

 seems, however, to be high in most cells except in resting muscle, 

 where most of the phosphate is bound to creatine. Phosphate is 

 generally considered to be the intracellular anion. How much of 

 this is really free phosphate and how much is labile phosphate 

 broken down by chemical manipulations remains to be determined 

 (34). 



In our opinion, the value of such schemes is limited because they 

 disregard controlling factors in the cell which undoubtedly must 

 regulate the routes of phosphate turnover— that is, the synthesis as 

 well as the breakdown of intermediates. The Pasteur effect cannot 

 be due merely to an "open" equilibrium; it must be due to specific 

 transmitter systems. Evidence for this is the fact that the 'linkage" 



