436 9. INHIBITION IN CELLS AND TISSUES 



have important bearings on competitive inhibition studies. It is actually 

 not known if these differences are due to the altered environment of the 

 enzyme when isolated or whether it is a true structural variation between 

 the enzymes in the two states. One factor of importance is probably the 

 existence of the enzyme at one of the numerous cell interphases. Catalase 

 can be adsorbed onto artificial interphases to give states from complete 

 activity to complete inactivity (Fraser et al., 1955). It has been suggested 

 that catalase in normal yeast cells exists in a partially unfolded condition 

 at some oil/water boundary, since extraction could increase the activity 

 manyfold. On the other hand, in some cases, extraction from the cell could 

 lead to partial unfolding or denaturation by contact of the enzyme with 

 substances from which it is normally separated. It is also conceivable that 

 an inhibitor within the cell could either directly or secondarily alter these 

 structural conditions so that the activity of an enzyme might change 

 without a direct attack being made upon it. The lipoprotein nature of 

 some enzymes within the cell may favor the stability of active struc- 

 tures and any dissociation of such complexes would change the properties 

 of the enzyme. 



TYPES OF INHIBITION UNIQUE TO ORGANIZED 



SYSTEMS 



Inhibitors may alter cell metabolism or function in a variety of ways 

 not possible in the simple isolated enzyme preparation. Sometimes the whole 

 cell is not necessary for these more complex types of inhibition, but in all 

 cases it requires the participation of several enzymes or a structurally or- 

 ganized metabolic system. It is not profitable at the present time to treat 

 such inhibitions by a completely quantitative approach because too many 

 unjustified assumptions must be made, but a semiquantitative formula- 

 tion may be useful in showing what experimental data are needed for a 

 more rigorous treatment. 



The True Enzyme Inhibitor Is Formed Metabolically from the Added 



Substance 



The substance presented to the cells may not itself be an enzyme inhi- 

 bitor but is chemically transformed through the mediation of the cell en- 

 zymes into an inhibitor. The substance from which the inhibitor is formed 

 will be called the precursor. This phenomenon is commonly designated as 

 lethal synthesis, an expression coined by Peters for the metabolism of 

 fluoroacetate into fiuorocitrate. Although the result may not be lethal, 

 this terminology is convenient and generally accepted. An excellent dis- 

 cussion of the more general aspects of lethal synthesis has been given by 



