896 METABOLISM OF THE CANCER CELL 12 



III. PROTEINS AND AMINO ACIDS 



(a) Composition 



The readers attention is directed to the following reviews relative to protein 

 and amino acid composition of malignant tissues: Toennies (1947), Stern and 

 Willheim, chapter II (1943), Greenstein (1954, 1956) and Biserte (1953). The 

 compositional pattern of the proteins that constitute an integral part of all cells 

 or tissues undoubtedly play an important role in the function and destiny of the 

 organism. Up to this time, however, the biochemist has been vmable to discover 

 any such pattern of amino acids in proteins or any molecular features of these 

 macromolecules that would in any way characterize the proteins of normal or 

 neoplastic tissues. We may reasonably expect that the complex nucleoproteins 

 may be involved in malignant transformation and in the behavior of the cancerous 

 cell. This aspect will be further considered in a subsequent section. Also, some 

 important advances have been made in studying the immunological properties 

 of proteins derived from normal and neoplastic tissues (see Chapter 11). 



A striking resemblence of overall amino acid composition of a variety of nor- 

 mal and neoplastic tissues was noted by Sauberlich and Baumann (1951). In- 

 cluded in this study were analyses for the total concentration of each of 1 2 amino 

 acids of many normal tissues from different species and also of fibrosarcomas, 

 carcinoma and hepatomas. This approach did not reveal either quantitative or 

 qualitative differences that may occur in the individual proteins of these tissues. 



However, the application of end group and sequential amino acid analysis, as 

 employed by Sanger, Du Vigneaud and others, may reveal significant composi- 

 tional differences between protein components of normal and neoplastic tissues. 



Hydrolysates of mouse tumor and embryo were analyzed for amino acid con- 

 tent by Boman (1952). Lysine, taurine and tyrosine were reported to be present 

 in carcinoma but not in embryonic tissue. Also, more glycine, valine, serine and 

 alanine were found in carcinoma than in the embryonic tissue. Amino acid analy- 

 ses were carried out by starch column and paper chromatography on unhydrolyzed 

 and hydrolyzed alcoholic extracts of sarcomas and skeletal tissues of rats (Seibert 

 et al., 1954a). Several difTerences were noted between the normal and neoplastic 

 tissue extracts, of which the most significant was the free amino nitrogen which 

 constituted approximately 60% of the total nitrogen in extracts of tumor tissue 

 and 20% of the total nitrogen in the extracts from normal tissue. 



Several investigations have been made on the free amino acid patterns in normal 

 and neoplastic tissues. Lymphosarcomas have higher concentrations of alanine, 

 glycine and proline than normal lymphatic tissues (Kit and Awapara, 1953), but 

 aspartic acid and glutamine were lower in tumor than in the normal tissues. 

 Smith and Rossi (1954) also found that lymphosarcomas have a higher concentra- 

 tion of alanine and glycine. Taurine was also present in high concentration in 

 tumors, however proline, aspartic acid, serine and threonine occurred in lower 

 concentrations. Taurine, alanine and triiodothyronine, according to Christensen 

 et al. (1954) were present in high concentrations in Ehrlich mouse ascites carcino- 

 ma following in vitro incubation. Roberts and Borges (1955), and Roberts and 

 Tanaka (1956) concluded that the pattern of free amino acids in Yoshida ascites 



