412 2. ANALOGS OF ENZYME REACTION COMPONENTS 



Glucose-6-Phosphatase 



The hydrolysis of glucose-6-P in rat liver preparations (probably microso- 

 mal) is inhibited by glucose with a K^ around 29 mM (Langdon and Weak- 

 ley, 1957). This inhibition is noncompetitive with respect to glucose-6-P, 

 and it was postulated by Segal (1959) that the glucose competes with the 

 second substrate, water, for its site; the transfer of phosphate could occur 

 either to water or another molecule of glucose. If this is true, incorporation 



(1) Enzyme + glucose-6-P -^ enzyme-gIucose-6-P 



(2) Enzyme-glucose-6-P :^ enzyme-P + glucose 



(3) Enzyme-P + water ^ enzyme + Pt 



(4) Enzyme-P + glucose 5=^ enzyme-glucose-6-P 



of C^* from glucose-C^* into glucose-C^'*-6-P should occur and this was dem- 

 onstrated. It was shown that with the appropriate rate constants the re- 

 actions (l)-(4) (reaction (4) is of course the reverse of (2) and is included to 

 visualize competition between water and glucose) lead to noncompetitive 

 kinetics. A study of the inhibition of this incorporation by Hass and Byrne 

 (1960) showed that glucose is the most potent inhibitor of various sugars 

 tested. 



Miscellaneous Inhibitions 



Numerous other analog inhibitions of enzymes involved in carbohydrate 

 utilization have been reported, some of which have been summarized in 

 Table 2-21. These inhibitions along with those previously discussed point 

 to many mechanisms for the control of glucose metabolism. The complex 

 interplay between all the sugars and their phosphorylated derivatives with 

 respect to the inhibition of various enzymes in the different available path- 

 ways must always be borne in mind in work on intact cells. Many of these 

 enzymes are also inhibited to varying degrees by inorganic phosphate; hence 

 the level of phosphate can also be a regulating factor. Enzymes inhibited 

 by phosphate include phosphodeoxyribomutase, phosphoribose isomerase, 

 phosphoglucose isomerase, triosephosphate isomerase, glucose-6-P dehydro- 

 genase, enolase, glyceraldehyde-3-P dehydrogenase, phosphorylase, trans- 

 aldolase, transketolase, glucose-6-phosphatase, and ribulose-P carboxylase. 

 In many instances appreciable inhibition is exerted by 5-20 niM phosphate. 

 An interesting study of phosphate inhibition of transaldolase was made by 

 Bonsignore et al. (1960) in which the following reactions were examined: 



Fructose-6-P + glyceraldehyde -> glyceraldehyde-3-P + fructose 

 Sedoheptulose-7-P + glyceraldehyde-3-P -> fructose-6-P + erythrose-4-P 



Phosphate inhibits the first reaction competitively with respect to fruc- 



