HEXOKINASES 385 



it impossible to determine the type of inhibition; actually some decrease 

 in the inhibition with increasing glucose was observed. As would be expected, 

 glucosone does not produce a Crabtree effect but blocks it (Yushok and 

 Batt, 1957). The inhibition of glucose fermentation in yeast depends on the 

 pH and the buffer system present (Hudson rnd Woodward, 1958). At pH 

 6.5 in phosphate buffer an inhibition of 73% of the anaerobic fermentation 

 of glucose was found at (glucosone) /(glucose) = 2, whereas no effect was 

 found at pH 3.5-4.5. The fermentation and phosphorylation of fructose are 

 inhibited more readily than with glucose, due to the higher ^,„ for fructose, 

 and the inhibitions are completely competitive with K^ for glucosone around 

 0.061 mM. Marked inhibition of anaerobic glycolysis in rat tissues by glu- 

 cosone was noted, brain being much more sensitive than tumor tissue; in 

 brain complete inhibition occurs with (glucosone)/(glucose) = 0.0067. The 

 susceptibility of brain glycolysis to glucosone is certainly much greater than 

 of any hexokinase studied and possibly there is an additional site of action. 

 In any event, these results provide sufficient explanation for the central 

 toxic actions of glucosone. Despite the fact that glucosone can be formed 

 in certain organisms (e. g., molluscan crystalline styles and red algae) and 

 can be metabolized in streptococci and mammals, it would appear that it 

 is not an important substance in intermediary metabolism and is not gen- 

 erally on the pathway for the synthesis of glucosamine (Becker and Day, 

 1953; Topper and Lipton, 1953; Dorfman et at., 1955; Bean and Hassid, 

 1956). There is thus no evidence that glucosone can participate in the reg- 

 ulation of carbohydrate metabolism, but the high susceptibility of brain 

 glycolysis suggests that one should withhold final judgment until the ab- 

 sence of glucosone in the body under various conditions has been demon- 

 strated. 



Inhibition of Phosphafructokinase by Cycle Intermediates 



The phosphofructokinase from sheep brain is quite potently inhibited by 

 certain cycle intermediates (see accompanying tabulation) (Passonneau and 

 Lowry, 1963). Although this is not strictly analog inhibition, it is worth 



