INHIBITORS OF CAEBOHYDRATE METABOLISM 411 



Yeast glucose-6-P dehydrogenase is inhibited competitively by glucos- 

 amine-6-P but in this case the affinity for the inhibitor is not as great 

 as for the substrate {K,,, = 0.058 mM, and K^ = 0.72 mM) (Glaser and 

 Brown, 1955). Neither mannose-6-P nor N-acetyl-D-gkicosamine-6-P inhi- 

 bits. Phosphate inhibits the yeast enzyme rather weakly but it is competitive 

 with respect to NADP. The enzyme from Prototheca zopfii, however, is inhi- 

 bited 13% by 0.07 mM phosphate, 43% by 0.14 mM, and 70% by 0.7 

 mM (glucose-6-P = 3 mM and NADP = 0.67 mM) (Ciferri, 1962). There 

 needs to be much more study of the inhibition of such enzymes if we are 

 to understand the controlling factors of carbohydrate metabolism. 



Phosphopentose Isomerases 



The phosphoribose isomerase of alfalfa is j^otently inhibited by 5-phospho- 

 ribonate and much less so by a variety of related substances (as shown in 

 the accompanying tabulation) (Axelrod and Jang, 1954). Since ribose-5-P 



was 2.5 mM, the 5-phosphoribonate is bound more tightly. However, even 

 19 mM 5-phosphoribonate does not inhibit the growth of Leuconostoc mes- 

 enteroides or Lactobacillus arabinosus in glucose medium; this could mean 

 that the pentose phosphate pathway is not necessary for growth of these 

 organisms or that the inhibitor does not penetrate readily. The Ophiodon 

 elongatus muscle enzyme is also inhibited by 5-phosphoribonate but less 

 potently (28% inhibition at 0.5 mM and 45% at 5 mM) (Tarr, 1959). 



The phosphoarabinose isomerase of Propionibacterium pentosaceum is not 

 inhibited by D-ribose, D-xylose, D-arabinose, L-arabinose, ribose-5-P, and 

 glucose-6-P at 10 times the concentration of arabinose-5-P (Volk, 1960), 

 and the phosphopentose isomerase of EcJiinococcus granvlosiis hydatid cysts 

 is not inhibited by glucose, fructose, glucosamine, glucose-6-P, fructose- 

 6-P, and mannose-6-P at 4 mM (Agosin and Aravena, 1960). However, the 

 latter enzyme is inhibited 51% by 1.2 mM dihydroxyacetone-P and 54% by 

 4 mM dihydroxyacetone, so that conditions favoring accumulation of these 

 substances might suppress the alternate pentose-P pathway, which could 

 be important in the results obtained with iodoacetate or D-threose-2,4-diP. 



