54 



INTERMEDIARY METABOLISM AND GROWTH 



but are highly characteristic for a given tissue (Roberts and Frankel, 1949; Kit, 

 1953; Kit and Awapara, 1954). Following a prolonged fast, a decrease is observed 

 in the concentrations of amino acids related to the glycolytic and tricarboxylic 

 acid cycle intermediates and an increase in some of the essential amino acids (Kit 

 and Awapara, 1954; Wu, 1954). However, the relative constancy of the free 

 amino acid concentration of most tissues is noteworthy. 



The patterns of the free amino acids of tumors differ from those of related normal tissues 

 in several respects. The concentrations of free alanine, glycine, and proline are rather high 

 in neoplastic tissues although the concentrations of ethanolaminephosphate, aspartate and 

 glutamine may be rather low (Roberts and Frankel, 1949; Kit and Awapara, 1953). The 

 interesting observation has been made that although the glutamine pool is low in growing 

 tumor tissues, this pool increases to the level found in normal tissues when the tumors 

 undergo regression (Roberts and Tanaka^ 1956). The low concentrations of glutamine in 

 tumors may reflect a high rate of utilization of the latter substance in anabolic processes. 

 Likewise, the glycine pool of tumor tissue may be high due to the fact that the beta carbon 

 of the glycine precursor, serine, is utilized at a considerably faster rate than the glycine 

 moiety. The high concentration of alanine is in all probability related to the rapid aerobic 

 glycolysis of tumors. 



The concentration of the essential amino acids has been measured in various 

 animal tissues (Schurr et al., 1950; Solomon et al., 1951). These amino acids and 

 proline are generally found in concentrations ranging from about 0.2-1.5 [jimol/g 

 wet weight of tissue. The concentration of free methionine is very low. On the 

 other hand, the concentrations of glutamic, aspartic, glycine, serine, alanine, 

 glutamine, ethanolamine phosphate, glutathione, and taurine are usually much 

 higher, and in some cases may be as high as seven micromoles per gram wet weight 

 of tissue, y-aminobutyric acid occurs at relatively high levels in brain tissue, while 

 low levels of glycerolphosphorylethanolamine are also frequently encountered in 

 tissue extracts. 



2. Amino acid relationships 



Information as to the metabolic relationships among the amino acids and between 

 the amino acids and intermediates of glycolysis and the tricarboxylic acid cycle 

 may best be illustrated by citing the experiments of Abelson and coworkers (Abel- 

 son, 1954; Abelson and Vogel, 1955). E. coli cells or yeast cells were grown 

 in the presence of glucose-''*C, ''^CO:, or some other labelled substrate. At the 

 end of the experiment, the cell proteins were hydrolyzed and the radioactivity of 

 each of the amino acids was determined. In parallel experiments, exogenous 

 unlabelled amino acids or other metabolites were added to the culture medium. 

 Certain of the exogenous amino acids, depressed the incorporation of the labelled 

 glucose or carbon dioxide into related amino acids. The results obtained provide a 

 measure of the relative utilization of competing exogenous and endogenous amino 

 acids. For example, in the presence of non-labelled exogenous aspartate, the in- 

 corporation of labelled glucose into the following amino acids of £. coli cell protein 

 is depressed : aspartate, threonine, isoleucine, methionine, and lysine. There was 

 also a lesser reduction of the incorporation of label into the glutamic acid and 

 proline of the protein. One may thereby infer that a metabolic relationship exists 



