goo METABOLISM OF THE CANCER CELL 12 



Further evidence has been presented by Rabinowitz et al. (1955) that glycolysis 

 can supply energy for the incorporation of amino acids into the proteins of tumors. 

 The incorporation of radioactive leucine, valine, lysine, phenylalanine and 

 methionine into proteins of Ehrlich ascites carcinoma was supported anaerobically 

 under conditions of active glycolysis. Nyhan and Busch (1956) added labeled 

 glutamate to systems containing slices of liver, kidney or Walker 256 carcinoma. 

 Specific activities of tumor, kidney and liver proteins were 63, 39 and 27 CPM/mg, 

 respectively, in unsupplemented systems; 117, 39 and 24 CPM/mg respectively, 

 when these systems were supplemented with o. 006 ^\/ glucose. In systems containing 

 L-lysine-U-''*C the ratio of specific activities of tumor, kidney and liver was 

 7.5:1.7:1 compared with ratios of 2.4:1.4:1 with labeled glutamate. The oxida- 

 tion of glutamate in the tumor was suppressed by glucose, but enhanced the 

 protein labeling. The uptake of histidine is coupled with the glycolytic splitting 

 of glucose according to Negelein (1952). Slices transplanted rat tumor had an 

 uptake of L-histidine of almost ten times that of normal liver. D-Histidine was 

 taken up at only 20% of that observed for the L-isomer. The in vitro formation of 

 amino acids from labeled glucose in normal mouse tissues, rat thymus, rabbit 

 appendix, several lymphosarcomas, Ehrlich ascites tumor and mouse melanoma 

 was investigated by Kit and Graham (1956a). High levels of radioactivity were 

 attained in the free glycine, serine and alanine of the lymphomas and the ascites 

 tumor. Also of interest was the relatively high activity of the alanine and the low 

 activity of serine in the melanomas. Radioactivity of the glycine and serine of the 

 normal tissues was considerably below that of the tumors. Kit (1955a) has pro- 

 posed the following mechanism for the biosynthesis of glycine and serine in lym- 

 phosarcomas : 



acetate > oxalacetate < > pyruvate 



I 



glucose -^ hexose phosphate < > phosphogluconate 



t 

 ribose ■ 



serine < phosphoserine < '- phosphohydroxypyruvate 



i 

 glycine 



The conversion of acetate-2-''*C to glycine was inhibited by glucose, serine, 

 fluoride and malonate. Some labeling of glycine was obtained when ribose- '"^C 

 was added to the system. 



Further observations have been made with respect to the uptake of amino acids 

 by normal and cancerous tissues (Roberts and Tanaka, 1956; Christensen and 

 Henderson, 1952; Heinz, 1954; Riggs et al., 1954; Rutman et al., 1954; Reid et al., 

 1952). Muller (1953) found that transplanted rat tumors exhibited high uptake of 

 histidine, serine and asparagine. Intermediate uptakes were noted for glycine, 

 alanine, threonine and phenylalanine while glutamic acid and arginine were 



