HEXOKINASES 



381 



Rat intestinal mucosa hexokinase is inhibited by glucose-6-P but only 

 about one-tenth as readily as the brain enzyme (Sols, 1956). The hexokinase 

 of Schistosoma is strongly inhibited by glucose-6-P when glucose or mannose 

 is the substrate, but fructose phosphorylation is unaffected (Bueding and 

 MacKinnon, 1955). Ascites tumor hexokinase behaves like the brain enzyme 

 and the K, for glucose-6-P is 0.4 mM (McComb and Yushok, 1959). Thus 

 inhibition of various hexokinases by glucose-6-P has been observed, but the 

 original observation that the yeast enzyme is resistant cannot as yet be 

 explained. 



Inhibition by D-Glucosamine and Derivatives 



Glucosamine (2-amino-D-glucose) is phosphorylated by brain hexokinase 

 (Harpur and Quastel 1949) and it was postulated by Quastel and Cantero 

 (1953) that it might be carcinostatic through ATP depletion. However, it 

 also competitively inhibits glucose phosphorylation and any carcinostatic 

 activity it possesses would be more likely related to this. Maley and Lardy 

 (1955) thus attempted to find a more potent inhibitor among the A^-acylated 

 derivatives and were quite successful, as shown in the accompanying tabu- 

 lation. Furthermore, these derivatives are not phosphorylated. 



Ki (mM) 



OH 



NH, 



CHoOH 



NH— CO 



O 



Q-D-Glucosamine 



iV- Benzoyl- o-D -glucosamine 



Before considering the nature of this inhibition, let us examine other 

 hexokinases to determine how widespread is the susceptibility. The fructo- 



