II CARBOHYDRATES AND LIPIDS 887 



the formation of protein in Ehrlich carcinoma cells, reported that the oxidative 

 metabolism was blocked by KCN or NaN3, while the glycolytic process was 

 blocked by the elimination of glucose. When the respiratory processes alone were 

 active the rate of assimilation of radioactive methionine into the proteins was 

 approximately half of that observed when the glycolytic process was active. 



These observations regarding respiration and glycolysis in neoplastic cells repre- 

 sent a small proportion of the investigations that have been carried out in this 

 important area. From the seemingly unending list of publications the impression 

 may be gained that an explanation for the high glycolytic activity of tumors 

 should be readily available. Upon closer examination of these experimental results 

 it soon becomes apparent that a really concerted effort is lacking. The investiga- 

 tions encompass a wide range of tumors — animal and human, ascites and solid types, 

 variations in methods and other variables, making the task of critical correlation 

 or proper evaluation extremely difficult. Indeed, many of these findings appear to 

 be completely isolated. A thorough understanding of the methods and the par- 

 ticular systems employed is an essential prerequisite for the planning of studies 

 to establish or to build upon existing concepts. 



The literature generally supports the concept of a high anaerobic and aerobic 

 glycolysis in cancerous cells. Also there seems to be little doubt that the glycolytic 

 pathway in tumors follows the established Embden-Meyerhof scheme for normal 

 tissues. Most investigators are in agreement that this glycolytic pathway may 

 account for 60-90% of the COj that is derived from the glucose utilized in 

 tumors. A majority of the findings point to a rather uniform metabolism for malig- 

 nant tissues. Certainly this glycolytic pattern is of significance in the origin or 

 the subsequent growth of tumor cells. In attempting to account for or explain this 

 metabolic difference in too general terms, much of the real significance of these 

 important findings has been overshadowed. The concept of a faulty or impaired 

 respiration in tumor cells has little meaning in terms of specific reactions or com- 

 ponents of the cells. The available evidence would indicate that all of the enzymes 

 as well as the intermediate components involved in the complete breakdown of 

 glucose are present in the cancerous cell. Factors that may account for this differ- 

 ence include : disturbance in electron transport, differences in membrane perme- 

 ability between normal and cancerous cells thereby limiting the exchange and 

 availability of essential metabolites, relative differences in the concentration of 

 specific enzymes or cofactors in tumor cells such as cytochrome, cytochrome 

 oxidase etc., the relation of lipid oxidation to the overall metabolic pattern, and 

 finally, the possibility of the inherent response of malignant cells to the hormones 

 of the pituitary, adrenal, pancreas, and thyroid glands which virtually control 

 the various steps of carbohydrate metabolism. Further discussion of these important 

 areas of glucose and lipid metabolism will appear in subseqvient sections. 



Recently, Potter (1956) has proposed a concept of respiratory enzyme balance 

 to replace that of a faulty respiration. The respiration of the tumor is geared to the 

 synthesis of the many essential constituents of growth. This includes the many 

 phosphorylative reactions and the formation of the constituents of the nucleic 

 acids. Potter relates respiratory balance to the biosynthesis of deoxyribonucleic and 

 and ribonucleic acids as presented in Fig. i. 



Literature p. gig 



