CHAPTER 1 



PERSPECTIVES OF METABOLIC 

 INHIBITION 



Living cells are characterized by a complex and beautifully organized 

 pattern of chemical reactions mediated and directed by enzyme systems. 

 These reactions provide the energy necessary for the various functions of 

 the cell and support the synthesis of material upon which the cell depends 

 for maintenance, growth, and multiplication. One basic way of expressing 

 this pattern is to consider the flow of energy through the cell: the intake of 

 the potential energy resident in prospective substrates, regulated by mem- 

 brane permeability and occasionally by active processes; the release of this 

 energy into utilizable forms during the oxidative degradation of these sub- 

 stances, wherein the energy is fractionated and distributed in smaller units; 

 the transfer of this energy, perhaps through several steps, until it is mani- 

 fested in terms of some evident cellular activity, such as secretion, active 

 transport, impulse conduction, movement or emission of radiation; the 

 partial flow of the energy into the complex compounds synthesized either 

 for primarily structural purposes or for the metabolic and functional sys- 

 tems of the cell, for even the enzymes themselves must be assembled using 

 the energy derived from their catalyzed reactions; and, finally, the inevi- 

 table release of a certain fraction of the energy as heat, since energy transfer 

 and utilization cannot be completely efficient. If one were acquainted with 

 the full pattern of this energy flow and the means by which it is organized, 

 one could be said to understand the nature of life. 



The application of enzyme inhibitors to cells or their aggregates is one of 

 the ways in which the scientist attempts to penetrate into the nature of 

 living material and its transformations. This approach pertains to that class 

 of investigations in which a perturbation is induced in a complex system for 

 the purpose of understanding better the initial normal state. Such a proce- 

 dure must be quantitative to be fully effective. Also the primary pertur- 

 bation produced should be as small as possible, consistent with the sensi- 

 tivity of the methods of measurement, in order to reduce secondary phe- 

 nomena to a minimum. The normal state of a biological system should not 

 be conceived as a vague ensemble of simultaneous processes, but as a per- 

 fect balance of complex chemical and functional activities superimposed 



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