DISTRIBUTION OF INHIBITORS IN PLANTS 405 



Correlation of Enzyme Inhibition with Tissue Distribution 



In some cases a specific effect on an enzyme in a particular tissue may 

 be correlated with a high concentration of the inhibitor in that tissue. The 

 inhibition of renal succinic dehydrogenase by mercurials, without alteration 

 of this enzyme in other tissues, can certainly be related to the specific 

 accumulation of mercurial in the kidney tubular cells (Handley and Lavik, 

 1950). When chlormerodrin-Hg-°^ is administered to rats or dogs, the 

 kidney /plasma ratios run from 50-1300 while in all other tissties examined 

 the tissue /plasma ratio is less than unity (Giebisch and Dorman, 1958). 

 Indeed, there may be a correlation between the mercurial concentration 

 in the proximal and distal segments, and the degree of inhibition of succinic 

 dehydrogenase in these regions (Cafruny and Farah, 1956; Cafruny et al., 

 1955). 



The inhibition of cholinesterase by diisopropylfluorophosphate in various 

 tissues parallels the concentration of the inhibitor as determined by P^^ 

 analysis (Jandorf and McNamara, 1950). The time curve for the inhibi- 

 tion of erythrocyte cholinesterase follows closely the curve for P^^ concentra- 

 tion over 3 weeks, but in the plasma the P^^ decreases rapidly although 

 the cholinesterase remains inhibited for some time (this is probalby due 

 to the very small amount of P^- attached to plasma cholinesterase, the 

 larger nonbound P^^ having left the blood rapidly). A similar situation has 

 been reported for the inhibition of monoamine oxidase l)y iproniazid in 

 rats (Hess et al., 1958). The inhibitor enters brain, muscle, and liver rapid- 

 ly and the monoamine oxidase is inhibited completely almost at once. 

 However, the iproniazid concentration in these tissues falls off rapidly 

 (within 20 hr) but the inhibition persists for 3 to 6 days or longer. The 

 results for liver are shown in Fig. 8-2. The explanations suggested were: 

 (1) the enzyme may be irreversibly destroyed by the inhibitor and activity 

 does not return until new enzyme is synthesized, or (2) the inhibitor may 

 be irreversibly incorporated into the enzyme (the enzyme concentration 

 in the tissue being so low that attached inhibitor would not be detected), 

 or (3) the continuing inhibition may be due to some degradation product 

 of the inhibitor. For iproniazid the explanation is not known but DFP is 

 partially incorporated into the cholinesterase molecule. Reversible mono- 

 amine oxidase inhibitors, such as harmaline, show a more normal behavior, 

 in that enzyme inhibition ceases with the disappearance of the inhibitor 

 from the tissue. 



DISTRIBUTION OF INHIBITORS IN PLANTS 



Certain aspects of inhibitor distribution are quite similar for both the 

 higher plants and animals but special factors of importance only to plants 

 must be considered. There is regrettably little information from analyses 



