130 1. MALONATE 



intermediates in dog muscle as described above for rat muscle, but in ad- 

 dition there is an inhibition of the accumulation of fructose-l,6-diP, so 

 that some inhibition of a proximal step in glycolysis seems likely. Of the 

 four enzymes involved previous to fructose-l,6-diP, only phosphogluco- 

 mutase is sensitive to malonate, 40% inhibition being produced by 60 mM 

 malonate and 76% inhibition by 120 mM malonate. Thus a secondary site 

 for the inhibition of glycolysis is likely. Other mechanisms may be involved 

 in intact muscle cells. 



Effects on the Distribution of C" from Labeled Glucose 



If glucose is metabolized exclusively by the Embden-Meyerhof glycolytic 

 pathway and no initial decarboxylation of glucose or the hexose phosphates 

 occurs (as it would if the pentose-P pathway were operative), malonate 

 should depress the formation of C^'^Og from glucose-1-C^* and glucose-6-C^* 

 equally. However, if the pentose-P pathway is important, malonate should 

 decrease the formation of C^^Og from glucose-6-C^* relatively more than from 

 glucose-1-C^*, and hence increase the C-l/C-6 ratio. The difference between 

 the C^'^Oo formed from these precursors is often taken as a measure of the 

 activity of the pentose-P pathway; this may not be strictly true because 

 every hexosephosphate which is decarboxylated may not pass through the 

 pentose-P pathway completely, but it is certainly the best evidence for 

 the relative importance of these two pathways. 



Experiments of this type were performed with slices of various tissues 

 from the rat (van Vals et al., 1956). The specific activities of the C^^Og 

 formed from C-1 and C-6-labeled glucose are essentially the same in the 

 controls, indicating the pentose-P pathway to be unimportant (see ac- 

 companying tabulation). Malonate increases the C-l/C-6 ratios, which was 



C-l/C-6 ratio 

 Tissue 



Control Malonate 30 mM 



taken as evidence for a malonate-induced appearance of the pentose-P 

 pathway, although it would account for only a small fraction of the glucose 

 oxidized. In the lung and various mouse tumors, in which the pentose-P 

 pathway is operative normally (C-l/C-6 rations between 1.4 and 5.6), 

 malonate further augments the importance of the pentose-P pathway as 



