126 1. MALONATE 



tion) and fumarate. It was also shown that the rate of glycogen disappear- 

 ance in muscle brei is stimulated some 35% by malonate. These responses 

 were equated with the Pasteur reaction. Similar effects have been found in 



other tissues more recently. The rates of glucose utilization and of lactate 

 formation in brain slices are stimulated 13% and 44%, respectively, by 

 10 mM malonate (Takagaki et at., 1958), an effect much like that produced 

 by azide. Simultaneously less glucose is oxidized, the increased utilization 

 being diverted to lactate. Ehrlich ascites tumor cells exhibit a more rapid 

 rate of glycolysis when the oxygen tension is reduced and a similar response 

 is seen with malonate (Kvamme, 1957, 1958 d). When fumarate is added 

 to the malonate-blocked cells, glucose utilization and lactate formation are 

 suppressed. Strictly speaking, it is fumarate that gives rise to a Pasteur 

 reaction in the presence of malonate, just as the addition of oxygen does 

 in preparations previously anaerobic. Kvamme obtained data which led him 

 to conclude that this effect is mediated through changes in the concentra- 

 tions of inorganic phosphate and phosphate esters. The relationships 

 between glycolysis and mitochondrial oxidations are particularly well seen 

 in the reconstructed systems of Aisenberg et al. (1957). A supernatant frac- 

 tion from rat liver forms lactate from glucose and the addition of a mito- 

 chondrial suspension suppresses this markedly. Malonate partially prevents 

 this suppression; that is, added to the complete system, lactate formation is 

 increased. This stimulation of glycolysis occurs despite the fact that mal- 

 onate inhibits the glycolytic rate 15.7% in the supernatant fraction. This is 

 a good illustration of how malonate can produce different effects on glucose 

 metabolism, depending on the conditions and the factors controlling gly- 

 colysis. Stimulation of aerobic glycolysis by malonate, and a variety of 

 other inhibitors, is particularly well seen in thymocytes; malonate ac- 

 celerates lactate formation sigmoidally from 3 mM to 100 mM (Araki 

 and Myers, 1963). 



Malonate may have no effect on glucose uptake, or may inhibit it, in 

 other tissues. Chick chorioallantoic membrane infected with influenza 

 virus exhibits a 47.5% reduction in the endogenous respiration in the pre- 

 sence of 6 mM malonate, and the final virus titer drops to zero, but the 



