CHAPTER 16 



SPECIFICITY OF INHIBITION 



Specificity refers in general to the ability of an inhibitor to affect one 

 process more than others. This concept may be applied to any level of 

 organization. For example, the specificity may refer to species, tissues, 

 different functions, metabolic processes, or enzymes. Many instances of 

 species specificity are known and they are treated in a stimulating manner 

 by Albert in his "Selective Toxicity" (1960). A few examples will serve to 

 illustrate this type of specificity: the suppression or killing of pathogenic 

 organisms with minimal effects on the host (as the selective actions of 

 copper and the dithiocarbamates on fungi parasitic to plants), the killing 

 of certain weeds by dinitro-o-cresol while leaving crop plants unaffected, 

 the ability of urethane and certain naphthoquinones to inhibit tumor cell 

 growth more readily than the growth of normal cells, and the selective 

 effects of mercurials and arsenicals on bacterial and protozoal invaders. 

 Likewise, there are many examples of tissue specificity. The effect of an 

 inhibitor when it is administered to an animal is always selective to some 

 extent, inasmuch as certain organs or functions are altered before others. 

 Noteworthy examples would 1)e the remarkable specificity of alloxan on 

 the pancreatic islet cells, the renal effects of the carbonic anhydrase inhi- 

 bitors and the mercurials, and the central nervous system changes follow- 

 ing fluoroacetate. The cholinest erase and monoamine oxidase inhibitors 

 also show selective effects on those tissues or junctions where these enzymes 

 are functionally important in the determination of the neurohormone con- 

 centrations. Such specificity on the organism or cellular level has been 

 discussed in previous chapters in several connections, so that in the present 

 chapter emphasis will be placed on enzyme specificity. Much of species and 

 tissue specificity depends on the differential distribution of the inhibitors 

 and the presence or absence of the enzymes or metabolic systems attacked. 

 It is now necessary to inquire into the selective actions of inhibitors in 

 situations in which several possibly susceptible enzymes are present and 

 the inhibitors are at uniform concentrations. 



As Albert has pointed out, specificity of metabolic disturbance is well 

 documented and yet much of the trend during the past decades has been 

 to demonstrate a fundamental similarity in the enzymes and metabolic 



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