VOL. 4 (1950) GLYCOLYSIS IN PHARMACOLOGY I39 



Any abnormal cell, invading organism or abnormal metabolic event in the body 

 involving or using carbohydrate opens itself to this mode of attack, namely, to find 

 a chemical substance which will block or modify its use of carbohydrate but not affect 

 the use of carbohydrate by the normal cells of the host. In this manner the abnormal 

 cells or invading organisms can no longer use sugar for energy purposes and thus are 

 destroyed. Abnormal metabolism of carbohydrate may also be checked or diverted into 

 normal pathways in a similar manner. Since the carbohydrate is generally oxidized 

 by the invading organisms, two possibilities are available for blocking by enzymatic 

 inhibitors; a) in the oxidative chain and b) in the glycolytic system. In the cancer field, 

 for example, if an agent could be found which will block the use of glucose either by 

 oxidation or by glycolysis in the rapidly growing cells, growth would cease since these 

 cells depend mainly on the metabolism of glucose for their growth. Therefore, there 

 should be a constant search for compounds which inhibit glycolysis or the oxidation of 

 various sugars. Such a search may some day be rewarded with a differential inhibitor 

 which will block sugar utilization in the cancerous cell and not in the normal cell. Such 

 inhibitors have been found already for certain invading organisms and may well be 

 found for the cancer cell. A review of some of the literature in this field up to 1938 

 has been made by Gemmill^". 



Quinine and Atabrine: During the war, Evans and his associates made a very 

 intensive study of quinine and atabrine on glycolysis. This group demonstrated that 

 the glycolysis of the malarial parasite was similar to that of the phosphorylating gly- 

 colysis of yeast and muscle^^. Following these observations the effects of quinine and 

 atabrine were investigated^^ on this system from malarial parasites, yeast and mam- 

 mahan muscle. Atabrine inhibited hexokinase activity and the lactate dehydrogenase 

 in the parasite preparations. Both quinine and atabrine inhibited the yeast hexokinase 

 while quinine was inhibitory to the phosphorylase and the phosphoglucomutase from 

 rabbit's muscle. Lactate dehydrogenase from beef heart was very susceptible to atabrine 

 action. However, from the concentrations needed to inhibit these enzymes in the gly- 

 colytic systems, these authors concluded that the therapeutic site of inhibition is 

 probably in the oxidative cycle unless there is a possibility of a high concentration of 

 these drugs localizing inside the parasite cell. Bovarnick, Lindsay, and Hellerman" 

 attribute the inhibitory action of atabrine on the oxidation of glucose to an interference 

 of phosphorylation which is essential before glucose may be oxidized by the malarial 

 parasite. 



Naphthoquinones: There has been considerable attention given to the naphtho- 

 quinones in pharmacology in recent years. In addition to the discovery that vitamin K 

 has a naphthoquinone nucleus, these compounds have been investigated for their 

 antimalarial^*, fungicidaP^, antitubercular^^, and antibacterial actions^'. Some of the 

 naphthoquinones have the power to inhibit mitosis which makes them of interest from 

 the standpoint of tumor growth^^. Naphthoquinones inhibit acid formation in the saliva 

 which may aid in the prevention of tooth decay^^. 



Considerable work has been done to explain the action of naphthoquinones on a 

 possible enzymatic site. Wendel^o has described an inhibition of the oxygen uptake 

 and the use of carbohydrate in red blood cells parasitized with a malarial parasite. 

 Ball, Anfinsen, and Cooper^^ have made an extensive study of the inhibition of 

 oxygen uptake and have come to the conclusion that the inhibitory site is between cyto- 

 chrome c and b in the chain of respiratory enzymes. Bueding, Peters, and Waite^^ 

 References p. 142 j 143. 



