96 S. S. COHEN 



In intact animals the enzjone produces a fall of 50 % in the content of ENA 

 in Landschutz ascites tumor and effects a general slowing down of tumor 

 growth. On isolated tumor cells RNAase frequently produces an initial 

 apparent increase of RNA and protein, which is subsequently followed by 

 cell degradation. 



iv. Inhibition of Protein Synthesis. Protein metabohsm is influenced by 

 energy production; indeed, the nature of the couphng of these activities is at 

 the core of our problem. When the rat is fed a high protein diet, there is a 

 linear relationship between change in body weight and the amount of energy 

 source, i.e., carbohydrate or fat in the diet (Munro and Naismith, 1953). 

 When the synthesis and secretion of specific proteins, e.g., lipase and ribo- 

 nuclease, are studied in pigeon pancreas sUces in physiological saline, it is 

 found that the formation of these enzymes is abohshed by anaerobiosis, or 

 by a compomid imcouphng oxidative phosphorylation, e.g., 2, 4-dinitrophenol 

 (Schucher and Hokin, 1954). Secretion of the enzymes may be stimulated 

 without affecting synthesis. 



As might be expected, an exogenous source of amino acids will stimulate 

 protein production in a synthesizing tissue. A mixture of all the amino acids 

 is usually more stimulatory than are single amino acids or limited mixtures 

 of these. In certain systems one may study the removal of single exogenous 

 amino acids from the environment and their concentration within the cells. 

 As studied in Ehrlich mouse ascites cells, the concentration of glycine is also 

 strongly inhibited by anoxia, cyanide, and dinitrophenol (Christensen and 

 Riggs, 1952). Comparable phenomena have been observed in bacteria by 

 Gale (1953). 



A deficiency of a single essential amino acid will inhibit protein synthesis. 

 In the presence of the required amino acid, amino acid analogs wiU serve to 

 prevent protein synthesis. Thus, 5-methyl tryptophan wiU block tryptophan 

 utihzation in animals (Gordon and Jackson, 1935), plants (Kessler, 1956), 

 and bacteria (Fildes and Rydon, 1947; Cohen and Fowler, 1947) and inhibit 

 protein synthesis in general. 



Three classes of amino acid analogs may be recognized. These are: 



1 . Analogs, such as 5-methyl trj^tophan, which do not replace tryptophan 

 and block protein synthesis. 



2. Compounds, such as ^-fluorophenylalanine, which are incorporated into 

 protein instead of phenylalanine and tjrrosine and severely affect protein 

 specificity and function (Munier and Cohen, 1956). 



3. Compounds, such as selenomethionine, which replace methionine in 

 proteins, e.g., /3-galactosidase, but have only a relatively slight effect on 

 protein specificity and function (Cohen, G. N., and Cowie, 1957). 



The inhibitory effects of some antibiotics on protein synthesis will be 

 discussed in later sections. 



