INHIBITORS OF CARBOHYDRATE METABOLISM 407 



Ki is around 0.005 mM (Kahana et al., 1960). Another potent inhibitor that 

 is an intermediate in the pentose-P pathway is erythrose-4-P, for which 

 the K^ is 0.0007- 0.001 mM {K„, for fructose-6-P is 0.08 mM) (Grazi et al, 

 1960). Under conditions that would lead to an accumulation of erythrose- 

 4-P, more glucose-6-P might be diverted into the pentose-P pathway or, 

 if fructose-6-P is being metabolized, a negative feedback effect would be 

 exerted. A third potent inhibitor is glucosamine-6-P (Wolfe and Nakada, 

 1956), which on the T. spiralis enzyme is around 40 times more inhibitory 

 than 6-phosphogluconate, 0.06 mM inhibiting 64% when glucose-6-P 

 is 5 mM (Mancilla and Agosin, 1960). The deamination of glucosamine-6-P 

 in E. coli: 



Glucosamine-6-P -> fructose-6-P :f± glucose-6-P 



thus terminates at fructose-6-P initially because of the inhibition of the 

 second reaction, but eventually disappearance of glucosamine-6-P relieves 

 the inhibition and glucose-6-P is formed, another example of metabolic 

 regulation through inhibition. 



Aldolase 



This enz^Tne splitting fructose- 1,6-diP to glyceraldehyde-3-P and dihy- 

 droxyacetone-P has unfortunately been studied very little from the stand- 

 point of inhibition by hexose or triose phosphates. Yeast aldolase binds sev: 

 eral hexose phosphates quite tightly but splits them very slowly (Richards 

 and Rutter, 1961), as may be seen from the K/s and the relative reac- 

 tion rates (rate with fructose-l,6-diP as 1) in the accompanying tabulation. 



Inhibitor , ', Pielative rate 



(mM) 



Muscle aldolase splits these analogs, niueh more readily. The aldolase from 

 rabbit Ihuscle was found by Herbert et al. (1940) to be competitively 

 inhibited by fructose-6-P (31%), fructose (16.3%), and glucose (5.4%), the 

 percentages being for 20 mM inhibitor and fructose-l,6-diP. The difficulty 

 in interpreting these results lies in our ignorance of the preferred form of 

 the substrate (i. e., a or j3, p>Tanose, furanose, or linear) for the enzyme, 

 and the distribution of the substrates and inhibitors among these forms 

 under the experimental conditions. The values of K^ may be quite misleading 



