Ill 



PROTEINS AND AMINO ACIDS 899 



Zamecnik et al. (1951) concluded that there were no qualitative differences in the 

 metabolic pathway followed by neoplastic and normal tissues. Their findings did 

 indicate that the synthetic activities in tumors were directed more towards protein 

 formation and cellular growth rather than glycogen formation or storage. 



Studies involving the uptake of ■'^P have indicated that a phosphoprotein frac- 

 tion may be involved in the metabolism of normal and malignant cells (Griffin 

 et al., 1 951; Mclndoe and Davidson, 1952; Albert and Johnson, 1954). Kennedy 

 and Smith (1954) incubated Ehrhch ascites cells with inorganic ^^p. The specific 

 activity of the phosphoprotein residue as obtained by the Schneider procedure 

 did not differ appreciably from the acid insoluble fraction. Phosphoserine, iso- 

 lated from the hydrolyzed phosphoprotein fraction, did have a very high specific 

 activity. This high activity may be indicative of the utilization by the protein of the 

 phosphate energy of ATP. 



[c) Amino acid tnetabolism 



The attention of the reader is again directed to the chapter on intermediary 

 metabolism (Chapter i). This provides an excellent background for the 

 known metabolic pathways involving the amino acids. Extensive investigations 

 have been made in this area and the present discussion will of necessity be limited 

 to those studies involving malignant tissues or cells. Mention should be made of 

 the widespread application of radioisotopes and it will become increasingly ap- 

 parent that most investigators have utilized labeled amino acids or related me- 

 tabolites in the course of their studies. 



Busch and Baltrush (1954) injected acetate- i-^'^C intravenously into normal 

 rats and rats bearing carcinoma. One min, after injection of the labeled acetate 

 the glutamate, aspartate and succinate accounted for 33-75% of the total radio- 

 activity present in the normal body tissues and only 4-6% of the activity present 

 in the carcinoma tissue. Kit (1955) has carried out studies on the conversion of 

 acetate-2-''*C to glycine by cell suspensions of Gardner lymphosarcomas and 

 several normal tissues. The total radioactivity of glycine in tumor tissues exceeded 

 that of normal tissues and also several other tumors by a factor of eight. The Gard- 

 ner lymphosarcoma utilized this pathway to a considerably greater extent than 

 other studied tissues. In a subsequent study, Kit and Graham (1956) incubated 

 spleen or lymphosarcoma with glucose-''*C or acetate-2-^'*C. The free serine and 

 glycine of the tumor were highly labeled while the corresponding amino acids of 

 spleen contained little radioactivity. The formation of these two amino acids was 

 also investigated with glycerol- i-'^^C. After incubation with this labeled com- 

 pound, the free and protein bound serine and glycine of lymphosarcoma were 

 three to five times as radioactive as that of the splenic cells. The free and protein 

 bound aspartate and glutamate of the spleen were 2-6 times as radioactive as 

 that of tumors. At least 80% protein radioactivity of the tumor was due to glycine 

 and serine and less than 10% to glutamate and aspartate. Only 35% protein radio- 

 activity of the spleen was due to glycine and serine and approximately 50% to 

 aspartate and glutamate. These results are in agreement with those of Busch and 

 Baltrush (1954) and indicate the general inability of tumors to synthesize aspar- 

 tate and glutamate. 



Literature p. yig 



