398 



2. ANALOGS OF ENZYME REACTION COMPONENTS 



of available ATP, this secondarily reducing hexokinase activity, and the 

 uptake of sugars. The greater resistance of aerobic glycolysis and respira- 

 tion to 2-DG, compared to anaerobic glycolysis, may be due in part to the 

 higher ATP levels aerobically. The differential effects on the uptakes of 

 different hexoses (Fig. 2-13) might be explained on the basis of whether a 

 hexose is actively transported or not, and the steady-state rate of its 

 phosphorylation (e. g., galactose metabolism is not depressed as much as 

 that of glucose), and the different affinities of the hexoses for the hexoki- 

 nases. 



20 



15 



10 



5 ■ 



c 0^ 

 (% OF 

 ADDED ) 



10 



15 



20 



[ 2 - DG ) 



Fig. 2-13. Inhibition of hexose oxidation by 2-DG in isolated rat 

 diaphragm. Hexoses were 10 mM. (From Nakada and Wick, 1956.) 



A summary of the sites and mechanisms in the inhibition of carbohydrate 

 utilization by 2-DG would then include: (1) primary competitive inhibition 

 of certain hexokinases by 2-DG, (2) possible direct interference in the ac- 

 tive transport of hexoses into the cell, (3) inhibition of phosphoglucose 

 isomerase by 2-DG-6-P, (4) secondary reduction in transport and hexose 

 phosphorylation through depletion of ATP, and (5) possible inhibitions by 

 2-DG-6-P of glycolytic enzymes not yet examined. 



