The Nature and Diversity of Catalytie Proteins 



89 



rnent of resistance to antibiotics and to anticancer agents. Three means 

 of development of resistance appear probable, as follows: 



1. Gradual or sudden changes in key properties of an enzyme or 

 enzyme system. 



2. Changes in enzyme concentrations leading to altered routes of 

 utilization of former lethal syntheses. 



3. Exclusion of the agents from sensitive sites by permeability, 

 binding, or other changes. 



Comparative studies on highly purified enzymes from normal and 

 resistant tumor cells or bacterial cells have been extremly limited. 



Gene Region Governing PAB -enzyme 



I HI I I Mil II! II ll 111 DNA 1 



J V 



DNA fine 

 structure 

 controls 

 protein fine 



structure 



PAB-enzyme protein 



FIG. 9. Genetic control of fine structure of enzyme system using p-aminobenzoate 



(40). 



In an important paper some years ago, Kubowitz and Ott (41 > found 

 purified lactate dehydrogenase from normal muscle and from the 

 Jensen sarcoma arising from muscle to be closely similar if not 

 identical in catalytic and immunologic properties. With further study 

 of the biochemistry of cancer, an appreciation has developed that 

 cancer cells, like bacterial cells, show a remarkable and deadly ability 

 to adapt to their environment. Recent reviews, such as that of 

 Anderson and Law (42 ) , may be consulted for a summary of various 

 findings. The data point unmistakably to the conclusion that resistance 

 can arise from change in the properties of certain enzymes, although 

 in no instance to our knowledge has proof of such a change been 

 documented with a purified enzyme. Some examples where a change 

 in properties of key enzymes is strongly indicated include the 



