i 1. PERSPECTIVES OF METABOLIC INHIBITION 



SO abnormal as to resist our efforts at correction, we may desire to kill 

 them in order that they will not disturb the normal cells and cause eventual 

 dissolution of the organism, and again one looks towards a specific attack 

 on those fundamental differences that distinguish pathological cells from 

 normal ones. Recent work along these lines in carcinostasis would seem to 

 justify this approach. Furthermore, foreign cells may enter the organism 

 and endanger its survival, and here too one must examine the differences 

 between these invading cells and the tissue cells, the different flows of 

 energy, to progress intelligently in the development and use of agents de- 

 signed to block the vulnerable processes in the intruders. Much of modern 

 therapy depends upon such specific inhibition and almost every inhibitor 

 group to be discussed has been used in some way in diseased states. 



It may be worthwhile to outline briefly the importance of enzyme inhi- 

 bitors in certain fields of investigation. The enzymologist attempts to un- 

 derstand in ever greater detail the intimate mechanisms of enzyme action 

 so that he will have deeper insight into the energetic basis of living processes. 

 Inhibitors have played a major role in the mapping of enzyme reactions in 

 both time and space. Organic chemists use group-specific reagents to iden- 

 tify the groups in unknown compounds. Likewise, the use of substances 

 reacting specifically with protein groups provides a means of characterizing 

 the chemical pattern of the enzyme surface and, particularly if these sub- 

 stances interfere markedly with the catalyzed reactions, evidence is obtained 

 that the reacted groups are part of the active center, that region of the 

 enzyme primarily responsible for the activation of the substrate. We shall 

 have ample opportunity to see how successful such procedures have been 

 in elucidating the topography of these regions and hence in aiding our un- 

 derstanding of the kinetic mechanisms by which biologically important 

 compounds are transformed. The biochemist thus frequently applies inhi- 

 bitors to the study of isolated and purified enzymes as part of the program 

 of characterization, and certainly this is one of the most fascinating aspects 

 of biology on the molecular level. 



The study of molecular interactions in biological systems has been re- 

 tarded by the deficiency of accurate data and by the inherent complexities 

 of the forces that are involved, but the importance of this subject will 

 certainly necessitate an increasingly vigorous combined attack on these 

 problems by physicists, chemists, and biologists. The most significant inter- 

 actions are between proteins and various substances — inorganic ions, hor- 

 mones, lipids, drugs, nucleotides and nucleic acids, and dyes — or between 

 different proteins. Almost all of cellular activity involves such interactions. 

 There is much need for more work on the quantitative aspects of these 

 interactions and for accurate studies of purified systems. The interactions 

 of inhibitors with enzymes present one excellent system for such study 

 and the results of inhibition often allow the over-all energies of the interac- 



