Extraneous Agents and Cell Metabolism 101 



liver are therefore expected to be ketogenic. This is in fact 

 the case. Malonate, which prevents the conversion of succinate 

 to oxaloacetate, or ammonium chloride which diverts the 

 metabolism of a-ketoglutarate to glutamate are both ketogenic 

 (Recknagel and Potter, 1951; Krebs and Kornberg, 1956). 



Effects of extraneous agents on cell activities depending 



on energy supply 



What has been said so far all refers to the reactions supply- 

 ing energy. Another group of metabolic processes depends 

 on a supply of energy which must generally be available in the 

 form of ATP. To these belong all synthetic processes, (especi- 

 ally the formation of macromolecules from basic units), 

 active transport of solutes, active movement and chemical 

 processes associated with other specific functional activities 

 of the cells. Very little is so far known about the nature of 

 the enzymes concerned with these aspects of metabolism ; it is 

 not possible in this field to draw up schemes similar to those 

 representing the energy-supplying reactions. 



However, one general feature appears to be shared by 

 many extraneous agents which interfere with processes 

 depending on energy. Although it may not be possible to 

 define the chemical reactions which are obstructed, many 

 effects can be explained by the assumption that the interfering 

 agent is chemically similar to a physiological agent, and that 

 owing to this similarity it occupies the physiological site, thus 

 displacing the physiological agent from its normal position. 

 To quote examples, this mechanism may account for : 



(1) The growth inhibition by sulphonamides (which occupy 

 the position of ^-aminobenzoic acid) and by other anti- 

 metabolites like aminopterin (an antifolic acid agent), 6- 

 mercaptopurine (an antipurine agent) and halogen-substituted 

 phenylalanine derivatives (antiphenylalanine agents in pro- 

 tein synthesis). 



(2) The anticoagulant effects of dicoumarol which interferes 

 with the conversion of vitamin K into prothrombin. 



