390 2. ANALOGS OF ENZYME REACTION COMPONENTS 



ing importance of each enzyme, and it was pointed out that it is very dif- 

 ficult to assess the effects of such analogs in adult liver. 



Most of the emphasis recently has been placed on the inhibition of 

 phosphoglucose isomerase by 2-DG-6-P. This inhibition is competitive on 

 the enzyme from rat kidney (Wick et al., 1957), rat muscle (Ferrari et al., 

 1959), and ascites cells (Nirenberg and Hogg, 1958). The inhibition is reas- 

 onably potent (see tabulation for kidney enzyme) and it would be quite 



Glucose-6-P 2-DG-6-P 



{mM) (mM) 



% Inhibition 



I 0.5 9 



1 1 24 



0.5 1 79 



easy for the 2-DG-6-P concentration to become greater than the glucose-6-P 

 concentration in cells, especially as the former is usually not metabolized 

 and accumulates. The inhibition of the skeletal muscle enzyme is very simi- 

 lar. Unfortunately the inhibitions of 6-phosphofructokinase and aldolase 

 by 2-DG-6-P have not yet been adequately examined, so one is left with 

 phosphoglucose isomerase as the site of the primary block, the conclusion 

 of Wick et al. (1957). However, another possible site for inhibition is the 

 membrane transport system for glucose, as suggested by the work of Kipnis 

 and Cori (1959), and this might be by either 2-DG or 2-DG-6-P. Furthermore, 

 Nirenberg and Hogg (1958) reported that the metabolism of fructose-1,6- 

 diP is blocked by 2-DG-6-P and stated that some inhibition must occur 

 after the phosphofructokinase step (which could be on aldolase). Other 

 inhibitions on enzymes metabolizing glucose but not on the main glycolytic 

 pathway may be mentioned. Rat liver microsomal glucose-6-phosphatase 

 is inhibited weakly by 2-DG (Hass and Byrne, 1960), HeLa cell glucose-6-P 



