388 



2. ANALOGS OF ENZYME REACTION COMPONENTS 



neally, due to erratic absorption from the peritoneum (Ball and Saunders, 

 1958). After subcutaneous administration there is a blood peak at 15 min, 

 after which there is a gradual fall over 6 hr. In human subjects infused 

 intravenously with 50-200 mg/kg of 2-DG over 30-min periods, approxi- 

 mately 30% is excreted in the urine (Landau et al., 1958). 



The pathways of 2-DG metabolism have not been completely worked out. 

 The accompanying scheme shows some of the reactions encountered. The 

 phosphorylation by hexokinase to 2-DG-6-P would seem to be the most 

 important reaction, especially as 2-DG-6-P is not metabolized in most cells 

 and tends to accumulate. HeLa cells can oxidize 2-DG-6-P but much more 

 slowly than glucose-6-P (Barban and Schulze, 1961). Hexokinases for the 



deoxy-disaccharides 



2-deoxy-D-glucose 



6 -deoxy-D-glucono lactone 



^^ 2-deoxy-D-gluconate 



\ 



2-deoxy-D-glucose-6-P »- 2-deoxy-D-gluconate- 6- P 



i \ 



(oxidized) D-mannonate-6-P 



formation of 2-DG-6-P have been found in brain (Sols and Crane, 1953), 

 kidney, intestine, liver (Lange and Kohn, 1961 a), skin (Brooks etal., 1959), 

 diaphragm( Kipnis and Cori, 1959), HeLa cells (Barban and Schulze, 1961), 

 ascites carcinoma cells (McComb and Yushok, 1959; Lange and Kohn, 1961 

 b), and Neurospora crassa (Sols et al., 1960 b). The Michaelis constants for 

 2-DG are usually higher than for glucose (see tabulation) but the rates of 



phosphorylation are often comparable. It is interesting that a strain of 

 HeLa cells resistant to 2-DG has been obtained, and they are defective in 

 hexokinase or contain a hexokinase inhibitor; the phosphorylation rates for 

 2-DG, glucose, fructose, and mannose are all lower than normal (Barban, 

 1961). Resistance is also associated with a 5- to 10-fold increase in alkaline 

 phosphatase activity and this may partly account for the slower rate of 



