EFFECTS OF 2-DEOXY-D-GLUCOSE 395 



of hexose phosphorylation and glycolytic breakdown are controlled by these. 

 In brain slices, 10 mM 2-DG causes a 50% fall in creatine-P and almost 

 complete disappearance of the adenosine polyphosphates (Tower, 1958). 

 There is also a diversion of phosphate to the stable 2-DG-6-P so that a cer- 

 tain amount of phosphate is removed from glycolytic participation, as also 

 pointed out by Kiesow (1960 c). Furthermore, 2-DG has been shown to 

 inhibit the incorporation of P/^ into ADP and ATP in ascites carcinoma 

 cells 70% at 10 mM (Greaser and Scholefield, 1960). El'tsina and Beresot- 

 skaya (1962) determined P, and nucleotide levels in tumor cells exposed to 

 11 raM 2-DG and found marked decreases in ATP and ADP (see accompa- 

 nying tabulation). On the other hand, rat liver and kidney slices show no 



significant changes, a difference attributed to variations in the activity 

 and cellular location of hexokinases. McComb and Yushok (1964 a) also 

 reported marked falls in ATP in ascites cells within 12 min after exposure 

 to 2-DG, and a 65% net loss of the cellular adenine nucleotides. The disap- 

 pearance of nucleotides is at least partly accounted for by the phosphory- 

 lation of 2-DG by hexokinase, the formation of AMP mediated by adeny- 

 late kinase, the deamination of AMP to IMP, and the splitting of IMP 

 to inosine by 5 '-nucleotidase (McComb and Yushok, 1964 b). They observed 

 a steady rise in inosine, correlated with a rise and subsequent fall in IMP. 

 Changes in nucleotide levels should affect various phases of metabolism 

 which involve these substances, and this is well seen in the effects of 2-DG 

 on the oxidation of ethanol in yeast (Maitra and Estabrook, 1962). When 

 2-DG is added to previously starved yeast in the presence of ethanol, 

 there is acceleration of respiration and the oxidation of NADPH, accompa- 

 nied by a fall in ATP with an elevation of ADP. This stimulatory phase 

 lasts less than a minute and is followed by a depressed phase characterized 



