MULTIPLE ENZYME SYSTEMS 



mediate IRMP. It is equally probable that X-CHO (active 

 formyl donor compound) has a much lower K^ (higher affinity) 

 for enzyme E2 than it has for E3 and that the equilibrium of E^ 

 is toward IRMP. Then it would be necessary to have a large 

 concentration of X-CHO to satisfy E3 and to pull IRMP through 

 the carboxamidine compound to AMP. 



A consideration of the role of enzyme saturation and the 

 rate of the reacdon may be profitable in examining the reason for 

 accumulation of intermediates in a reaction sequence. It is 

 not always clear why such a serendipitous accumulation should 

 occur. Naturally it could be that a compound accumulates 

 because an enzyme is limiting as a result of its being less active or 

 being present in lower concentration than the preceding en- 

 zymes in the sequence. In at least one case there is evidence 

 that the accumulation of an intermediate results from the con- 

 ditions usually present in multi-enzyme systems which are op- 

 erating in a steady state. That is, under conditions which do 

 not allow saturation of the enzymes the relative rates of the re- 

 actions in question may be considerably different from the rates 

 which obtain at saturation. In the synthesis of hypoxanthine 

 by pigeon liver preparations (12) it has been established that 

 inosine-5 '-phosphate is an intermediate. Under certain con- 

 ditions this compound accumulates in the system. The over-all 

 reaction system may be considered diagrammatically : 



glycine \ 



sflutamine . ,. ta^ti 



•1 \. u ^ ) ^ intermediates > IMF > 



ribose-phosphate 



+ other precursorsj inosine ^ ' HX 



Whereas IMP accumulates in the system it is not because the 

 reaction IMP — > inosine cannot adequately handle the quantity 

 of IMP formed. This enzyme apparently is not saturated by 

 the IMP and is not able to form inosine rapidly under these cir- 

 cumstances. However, after the IMP reaches a given concen- 

 tration, the enzyme is able to convert it to inosine at a rate which 

 is equal to the rate of synthesis, and accordingly a constant level 

 of IMP results. A graph describing such results is shown in 



547 



