INTRODUCTION «> 



system that is able to reproduce typical metabolic reactions in vitro ^ 

 is discovered, the way will be open for experimental study. The chemical 

 compounds involved in each step of the process can be isolated in pure 

 form, and the effect of removing them from the system or replacing 

 them at various concentrations can be observed. The catalysts (enzymes 

 and coenzymes) which make the whole process possible can similarly be 

 studied one at a time, and, in general, each step can be subjected to 

 detailed examination. It is in this way that much of our knowledge 

 of metabolism has been acquired. 



A still newer technique, which promises to be of major significance in 

 unraveling the chemistry of metabolism, is based on the use of isotopes. 

 The widespread use of this method was made possible by the atomic 

 energy development. Eventually, this may well prove to have been 

 one of the most constructive and valuable results of that program. Iso- 

 topes of the common elements — C, H, 0, N, S, P, and others — are used 

 as metabolic "tracers" by incorporating <^e or more of them into some 

 substance normally involved in metabolism. The "labeled" metabolite 

 is then administered to the test organism. After a suitable interval the 

 distribution of the isotope in the various tissues or tissue components 

 of the organism is determined. Thus if a rat is fed glycine containing 

 N^^ in the amino group, and the purine compounds in the animal's tissues 

 are later found to contain N^^ in comparable amounts, it may be con- 

 cluded that glycine is concerned in the biosynthesis of purines, and 

 specifically that one of the nitrogen atoms in the purine ring came from 

 the amino group of glycine. Other examples of the use of isotopes 

 will be encountered throughout the text. 



Information about metabolic processes can also be obtained by block- 

 ing some particular process and then searching for a way to remove the 

 block. The desired effect can be obtained, for example, with antimetab- 

 olites, substances so similar to certain normal metabolites that they 

 get in the way of the latter but yet are unable to carry out their func- 

 tions. Again, it is often possible to produce mutants of lower organisms 

 {e.g., the mold, Neurospora) , which lack the power to carry out certain 

 metabolic reactions. In such cases it has frequently been observed that 

 the effect [e.g., gro^\i:h failure) of the block may be removed by ad- 

 ministering some apparently unrelated chemical. This indicates that 

 the counteracting agent may be the substance normally formed by the 

 blocked reaction. As an illustration, suppose an organism needs substance 

 A to serve as a catalyst for the transformation of B into C: 



B " C 



An antimetabolite of A would probably inhibit the growth of this organ- 

 ism, but this inhibition would be counteracted by C. 



^ In vitro means, literally, in glass and implies occurring outside an.v living thing. 



