EFFECTS OF MALONATE ON GLUCOSE METABOLISM 127 



uptake of glucose is unaffected (Ackermann, 1951). An example of a marked 

 inhibition was reported for guinea pig brain slices, glucose utilization being 

 reduced by 10 mM malonate in both normal and K+-stimulated slices (see 

 accompanying tabulation) (Tsukada and Takagaki, 1955). It may be ob- 



served that the amount of lactate formed per glucose consumed is increased 

 by malonate, but some of the lactate must be derived from other sources 

 than glucose. It is difficult to understand the discrepancy between these 

 results and those obtained later on the same tissue (Takagaki et al., 1958), 

 where a slight stimulation of glucose utilization by 10 mM malonate was 

 reported. There are so many different results obtained relative to the utili- 

 zation of glucose that it often appears each organism or tissue exhibits a 

 characteristic pattern of response. Malonate at 40 mM has relatively little 

 effect on the uptake of glucose by brain and kidney slices, depressing it 

 slightly in the former and perhaps accelerating it in the latter, but reduces 

 the C^^Og formed from uniformly labeled glucose 79% and 52%, respective- 

 ly, the O2 uptake being suppressed comparably (Cremer, 1962). Since much 

 less of the glucose goes to amino acids and proteins in the presence of mal- 

 onate (Cremer, 1964), it is likely that here there is an accumulation of 

 certain cycle intermediates, such as succinate, and of lactate. Succinate is 

 normally formed and released into the medium by Trypanosoma cruzi. 

 It is formed aerobically through both the glycolytic pathway and the cycle, 

 and by CO2 fixation; some must be metabolized through the cycle since 

 malonate elevates the succinate level even further (Bowman et al., 1963). 

 The uptake of glucose is increased almost 20% by malonate but there is no 

 change in C^^Oo formation, most of the excess glucose probably appearing 

 as succinate, acetate, and related anions. 



Direct Effects on the Glycolytic Pathways 



There is no evidence that any enzyme of the Embden-Meyerhof glycolytic 

 pathway is significantly inhibited by malonate at concentrations below 20 

 mM (Table 1-12), although some of the enzymes have never been investigat- 

 ed. Several of the enzymes in this pathway require Mg++, or a related cation. 



