394 



2. ANALOGS OF ENZYME REACTION COMPONENTS 



the C-l/C-6 ratio in brain slices remains the same when ghicose uptake is 

 reduced to one third by 2-DG (Tower, 1958). 



Since hexose uptake into cells is often coupled with phosphorylation, 

 one would expect 2-DG to inhibit this uptake by suppressing kinase activity 

 directly or indirectly. Lymph node cells treated with 2-DG until 2-DG-6-P 

 is formed and then washed free of 2-DG do not accumulate glucose, fructose, 

 or mannose, and lactate formation is markedly reduced (Helmreich and 

 Eisen, 1959). The uptake of glucose into chick embryo hearts is 35-45% 



ISO 



0, FORMED 



30 



60 



90 



(2-06) 



120 



mM 



Fig. 2-12. Effects of 2-DG on the glucose metabolism in Ehrlich ascites carcinoma 

 cells. Glucose-u-C* was 10 mM. Control for residual glucose taken from nonincubated 

 flasks with no 2-DG. Experiments 2 and 4 were averaged. (Data from Christensen 



et ah, 1961.) 



reduced by 40 mM 2-DG (Modignani and Foa, 1963) and into carrot slices 

 is reduced to about the same degree by 10 mM 2-DG, this inhibition not 

 being overcome by increase in glucose concentration (Grant and Beevers, 

 1964). 2-DG interferes with galactose uptake into mouse strain L cells but 

 not potently {K^ = 7.2 niM) (Maio and Rickenberg, 1962). It is quite likely 

 that these inhibitions are exerted predominantly by 2-DG-6-P. On the 

 other hand, the accumulation of a-methylglucoside, which is transported 

 into E. coli by the glucose carrier, is well inhibited by 1-DG, poorly by 

 6-DG, and not at all by 3-DG (Hagihira et al, 1963). Apparently 2-DG 

 is not as potent an inhibitor here as 1-DG. 



Another mechanism by which 2-DG could alter carbohydrate uptake and 

 metabolism is by changing the levels of Pj, ADP, and ATP, since the rates 



