124 1. MALONATE 



carboxylation, whereas the first equation assumes no external oxalacetate 

 source. If the inhibition on succinate oxidase is complete and glucose is 

 oxidized completely in the control, we may calculate the inhibitions for the 

 situations where in the presence of malonate the glucose is transformed into 

 the various oxidation products: to succinate with external oxalacetate 

 source (33%), to succinate in a closed system (58%), to acetate (67%), 

 to pyruvate (83%), and to lactate (100%). Of course, experimentally it is 

 probably impossible to achieve a complete cycle block with malonate, so 

 that the inhibitions will usually be less than the theoretical. These calcula- 

 tions also assume that the rate of glucose disappearance is not altered by 

 the inhibition. The degree of inhibition, therefore, even under these simple 

 conditions, will vary a good deal, depending on the terminal product of 

 glucose metabolism and thus on the enzymes and pathways occurring in 

 the cells under consideration. Actually, it is likely that various substances 

 will accumulate during glucose metabolism, and not only those given above 

 but others into which these substances can be metabolized. 



A strong inhibition of the oxygen uptake related to glucose metabolism 

 probably indicates the participation of the cycle in the oxidation, at least 

 when the malonate concentration is not unreasonably high. Thus, in the 

 instances shown in the tabulation and selected at random of inhibition of 



glucose respiration, one would conclude that the role of the cycle is impor- 

 tant, but no information on the exact mechanism or on the fate of glucose 

 in the presence of malonate may be obtained. However, in the cases of brain 

 mince and yeast, fumarate is unable to overcome the inhibition, so that 

 some doubt is introduced even into this interpretation. The inhibition of 

 the glucose oxygen uptake in parasitized erythrocytes is very similar to 

 that for the oxygen uptake associated with pyruvate oxidation, as expected 

 if the cycle is the terminal pathway for glucose metabolism. On the other 

 hand, there have been many reports that malonate, even at high concentra- 

 tions, does not inhibit the glucose respiration at all, and in these instances 

 little can be concluded because of the possibility that malonate does not 

 penetrate and that an adaptation of the glucose utilization occurs. The 



