STIMULATION OF METABOLISM BY INHIBITORS 



453 



more obvious ways in which stimulation could be produced will now be 

 considered briefly. 



I. Remotxd or inactivation of some inhibiting substance. This tyjje of stimu- 

 lation probably is more frequently observed in disintegrated cell prep- 

 arations and extracts because the breakdown of the normal organization 

 may expose an enzyme to substances from which it is usually separated. 

 The only well-established cases involve the removal of an inhibitory metal 

 ion. Thus chelating agents, such as EDTA or o-phenanthroline, or substan- 

 ces forming complexes with metal ions, such as cyanide, have been shown 

 to increase the activity of certain enzymes by removing traces of heavy 

 metal ions from the medium. Yet, because of this same ability to combine 

 with metal ions, these agents can simultaneously inhibit other enzymes 

 or eventually even the enzyme activated. Ions such as Ca"^"^ and Mg"^"*" 

 may also be involved and the effects of inhibitors such as EDTA or malo- 

 nate can sometimes be partially attributed to the reduction of the con- 

 centration of these ions. It is easy to stimulate ATPase activity with mal- 

 onate when either Ca"^"^ or Mg"^"^ is unfavorably high. 



The conditions necessary for stimulation when only one enzyme is pre- 

 sent are given by Reiner (1959, p. 173). The reactions are: 



S -f E — ES -^ E + P K, 

 Ii -f E - EI, K, 



I2 + E — EI2 A% 



I: + I2 ^ IJ. K,, 



If the amount of either inhibitor bound to enzyme is neglected, the reaction 

 rate is given by: 



F„,(S) 



Vi = 



(S) + K, 



1 + 



di) , (I. 



K, 



K, 



(9-10) 



where the free inhibitor concentrations are: 



di) 

 (I2) 



{Ii)t 



1 + [{h)IK,,] 





(9-11) 



(9-12) 



Ii will be assumed to be the inhibiting substance present with the enzyme 

 and I2 the inhibitor added; it is the possible stimulation by Ig we are now 



