CHAPTER 9 



INHIBITION IN CELLS AND TISSUES 



The previous chapters have been primarily concerned with inhibition 

 of enzymes isolated from cells and studied in artificial media. When at- 

 tention is turned to inhibition in intact living cells or whole animals, many 

 new problems are presented as a result of the increased organization and 

 complexity of the metabolic systems acted upon. Information obtained 

 on isolated enzymes is valuable at the enzyme level and inhibition studies 

 have contributed to our knowledge of the nature of active sites and enzyme 

 mechanisms. However, the most important aspects of enzyme inhibition 

 are the elucidation of the metabolic events and pathways in cells and or- 

 ganisms, the determination of the relationship between cell function and 

 metabolism, and the use of inhibitors to alter specifically certain processes 

 or depress selectively the growth of cells invading the organism. The full 

 importance of inhibitors as tools in biochemical, physiological, and clini- 

 cal research is manifested only when the inhibitors are applied to living 

 systems. The basic knowledge gained from isolated enzymes must be ex- 

 tended to these enzymes when they are integral units of the organized met- 

 abolic complex. The basic question immediately arises: what is the rela- 

 tion between inhibition observed on an isolated enzyme and the inhibition 

 of that enzyme in the cell? When the characteristics of a particular inhi- 

 bition are known from studies of the pure enzyme — the effect of inhibitor 

 concentration on the degree of inhibition, the type of inhibition, the rate 

 of inhibition, the reversibility, the various constants — one may inquire 

 as to how reliable these characteristics are when applied to the living cell. 

 Many important correlations and conclusions from the use of inhibitors 

 depend on the assumption that extra- and intracellular inhibitions are 

 similar or indeed identical. One would prefer to believe that what happens 

 outside the cell may actually happen within, but the matter is more com- 

 plex than has been generally assumed and there are now reasons for sug- 

 gesting that a well-balanced pessimism is not inappropriate. The statement 

 by Davenport (1956) well expresses the modern more realistic attitude: 

 "Only the most fortunate combination of circumstances will allow one to 

 relate quantitatively the action of an enzyme in an extract and its activ- 

 ity in the intact cell." 



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