132 1. MALONATE 



role during malonate inhibition. Nothing is known of the possible direct 

 effects of malonate on the pentose-P pathway. The production of C^^Og 

 from ribose-l-C^* is inhibited strongly by malonate in heart homogenates 

 (Jolley et al., 1958) and it is believed that ribose is metabolized in this 

 pathway, but the inhibition may reflect an action on the cycle. It is inter- 

 esting that fluoroacetate does not inhibit C^^Og formation very potently, 

 except at very high concentrations, so that some direct effect on ribose meta- 

 bolism is possible. The results of the experiments discussed above would 

 argue against this. D-Xylose and D-ribose-5-P are oxidized through se- 

 doheptulose-7-P in extracts of Pseudomonas hydrophila and this is not af- 

 fected by malonate at 20 mikf (Stone and Hochster, 1956). 



The only investigation of the effects of malonate on the general distri- 

 bution of C^^from labeled glucose is that of Romberger and Norton (1961) in 

 potato tuber slices incubated with uniformly labeled glucose for 3 hr (Table 

 1-19). The situation in this tissue is complex inasmuch as fresh slices do not 

 metabolize glucose appreciably, whereas 36-hr-old slices oxidize it quite 

 rapidly. In the aged tissue, CO2 production is inhibited 92% by 50 mM mal- 

 onate at pH 5, while the formation of CO2 in fresh tissue is stimulated 28%. 

 In the fresh tissue, they suggest that CO2 is formed mainly in the pentose-P 

 pathway and little through the Embden-Meyerhof sequence, but glycolysis 

 contributes more and more with time, so that the marked inhibition by 

 malonate in aged tissue is not surprising. The synthesis of sucrose accounts 

 for over half of the labeling from glucose-u-C^* and this is inhibited only 

 11% by malonate. After 3-hr incubation, however, one can deduce little 

 about the initial attack on glucose. It may be mentioned in this connection 

 that in Acetobacter xylmum, where the sole product of glucose assimilation 

 is cellulose, malonate at 10 mM does not inhibit the formation of cellulose. 

 Laties (1964) has investigated this problem in detail and found that dif- 

 ferent methods of aging result in metabolically different potato slices, 

 in that some exhibit a malonate-sensitive and some a malonate-resistant 

 respiration. In the malonate-sensitive slices the formation of C^^Og from 

 labeled glucose is almost completely abolished by malonate, whereas in the 

 malonate-resistant slices there is little effect by malonate on the production 

 of C^^Og. There is a similar correlation with respect to the effects of malonate 

 on glucose uptake. Since dinitrophenol does not interfere with glucose 

 uptake, one can eliminate depression of ATP formation by malonate as 

 responsible for the inhibition of the uptake in sensitive slices. Laties con- 

 sidered the possibility that increased citrate levels might inhibit phos- 

 phofructokinase, but the mechanism is not yet well understood. 



Effects of Tissue Age on the Response of Glucose Metabolism to Malonate 



We have seen above that aging of potato slices increases their sensitivity 

 to malonate with respect to glucose oxidation. It might be expected that 



