INHIBITION OF ENZYMES 779 



the protector may be relatively ineffective against high concentrations, 

 as in the effects of arginine on the inhibition of its oxidative decarboxylation 

 (see accompanying tabulation) (Van Thoai and Olomucki, 1962). In most 



% Inhibition 



p-MB 



p-MB alone p-M.B + arginine 10 mM 











43 



61 



reports it is difficult to decide if the protection is simply due to a slowing 

 of the rate of inhibition or to a true effect on the final equilibrium inhibi- 

 tion, since measurements are often made over arbitrary time intervals. It 

 is evident that it is easier to slow down an inhibition than to modify its 

 final level; enough substrate, coenzyme, or cofactor to saturate the enzyme 

 substantially will quite markedly slow the reaction of the enzyme with 

 the inhibitor, but the final inhibition need not be significantly changed, 

 particularly with the mercurials which are usually bound tightly, if slowly. 

 Most investigators have noted that although the protectors in Table 7-9 

 are effective when present during the development of the inhibition, they 

 do not reverse the inhibition at all once it has reached a steady level, this 

 apparently indicating that most of the protection results are fundamentally 

 due to a slowing of the rate of inhibition. 



Occasionally two components of the enzyme reaction, forming a ternary 

 complex with the enzyme, protect more than each component alone. This 

 is the situation with malate oxidative decarboxylase, the protections by 

 malate and Mn++, or malate and NADP, being additive; the protections 

 by Mn++ and NADP are not (Rutter and Lardy, 1958). It may also be the 

 case with liver alcohol dehalogenase, ethanol and NAD protecting more 

 than either one alone (Yonetani and Theorell, 1962). In one situation, aspar- 

 tate carbamyltransf erase, neither substrate alone protects, but together they 

 do so quite effectively (Reichard and Hanshoff, 1956). An example of pro- 

 tection by a reversible inhibitor is the reduction in the inhibition of succinate 

 dehydrogenase by p-MB or Hg++ in the presence of oxalacetate (Stoppani 

 and Brignone, 1957). Actually, an effective competitive inhibitor might be 

 expected to protect better than the substrate. 



The information derived from protection experiments is frequently not 

 as reliable as commonly assumed, for reasons to be discussed in Chapter 1, 

 Volume III. The fact that the action of a mercurial is reduced by a sub- 



