EFFECTS OF MALOXATE ON GLUCOSE METABOLISM 131 



determined by C-l/C-6 ratios, which are increased to vakies between 4 

 and 125. A similar situation has been encountered in sheep thyroid shoes 

 (the results of three experiments are averaged in the accompanying tabu- 

 lation) (Dumont, 1961). The formation of C^^Oofrom glucose-6-C^* is inhibit- 



Ci*0, Control Malonate 100 mM 



ed strongly, whereas that from ghicose-1-C^^ is scarcely affected. This, of 

 course, indicates an almost complete block of the cycle, which is not sur- 

 prising at this high malonate concentration, but it also suggests a greater 

 participation of the pentose-P pathway in the presence of malonate. These 

 results are perhaps more understandable in the light of the glycolytic 

 inhibitions by high malonate concentrations discussed in the previous 

 section. Quite different results were obtained in electrically stimulated rat 

 ventricle strips (see accompanying tabulation) in which the pentose-P 



Ci^O, Control Malonate 5.6 mM 



pathway is presumably not important, malonate at this concentration 

 having little effect on glucose utilization (Rice and Berman, 1961). It is 

 possible that higher concentrations of malonate would produce changes 

 such as observed with other tissues. However, this concentration of mal- 

 onate is quite effective in modifying ventricular function. 



An indirect mechanism for the acceleration of the pentose-P pathway by 

 malonate may involve the levels of NADP and ATP in the tissues. The oxida- 

 tive decarboxylation of glucose-6-P to initiate this pathway requires NADP, 

 the concentration of which may be changed due to the action of malonate on 

 the cycle. Also the phosphorylation of fructose-6-P in the Embden-Meyerhof 

 pathway requires ATP, the level of which may be reduced by high concen- 

 trations of malonate. However, little is known about the control of the 

 pentose-P pathway and further experiments are needed to elucidate its 



