EFFECTS OF MALONATE ON LIPID METABOLISM 137 



10 raM malonate (Blakley, 1952). The rate of oxidation of decanoate by 

 Serratia marcescens is also not affected by 10 mM malonate, although 

 20 m.M inhibits somewhat (Waltman and Rittenberg, 1954). Geyer and 

 Cunningham (1950) stated that their data indicated no inhibition directly of 

 octanoate oxidation in liver by 5 mM malonate (this work will be discussed 

 in greater detail later). 



On the other hand, Lehninger and Kennedy (1948) reported that 10 mil/ 

 malonate stronglj' inhibits octanoate oxidation in particulate suspensions, 

 from rat liver. Not only is the respiration from the oxidation inhibited 

 but the utilization of octanoate is almost completely suppressed. The ad- 

 dition of malate or oxalacetate reduces the inhibition only partially, the 

 utilization of octanoate still being inhibited around 70%. It may be noted 

 that the total Mg+"'" concentration in these experiments was 0.25 mM, 

 which is quite low, so that malonate could have inhibited by depletion of 

 this cofactor. An interesting point is that the strain of rats used is very 

 important, since 10 mM malonate inhibits octanoate oxidation 25% in 

 preparations from livers of Sprague-Dawley rats, but in preparations made 

 from a heterogeneous stock colony 2 mM malonate inhibits 50-75%. 

 Such differences in strain behavior may explain some of the discrepancies in 

 the reports on malonate inhibition. Weinhouse et al. (1949) found that 

 20 mM malonate almost completely blocks the oxidation of octanoate in rat 

 liver slices and that fumarate only partially overcomes this, suggesting to 

 them that malonate must have some action other than on succinate oxidase. 

 In several instances malonate has been found to inhibit the oxygen uptake 

 from fatty acid oxidation very potently. Butyrate respiration in peanut 

 mitochondria is inhibited 75% by 6 mM malonate and the formation of 

 C^^Og from butyrate-l-C^* is depressed even more strongly (Stumpf and 

 Barber, 1956). Malonate at 10 mM inhibits the oxidation of octanoate by 

 carp liver mitochondria 80% (Brown and Tappel, 1959). In suspensions of 

 particulates from desert locust thorax, butyrate oxidation is inhibited 70% 

 by malonate at concentrations as low as 1 mM and maximally 85% (Meyer 

 et al., 1960). The oxidation of octanoate- 1-C^* and myristate-1-C^* by sub- 

 cellular particles from the lateral line of the rainbow trout, as measured 

 by the C^^Oj released, is reduced 95% by 10 mM malonate (Bilinski and 

 Jonas, 1964). One of the most sensitive systems is found in the oxidation of 

 linolenate in liver mitochondria of vitamin E-deficient chicks, 0.25 mM 

 malonate inhibiting 40% (Kimura and Kummerow, 1963). These examples 

 must be interpreted as indicating either a direct or an indirect inhibition 

 of the helix by malonate. Finally, it was stated by Mudge (1951), on the basis 

 of unpublished experiments, that malonate inhibits fatty acid oxidation 

 more strongly than succinate dehydrogenase in kidney particulate prepa- 

 rations. The possibility of effects on the helix must therefore be entertained 

 on the basis of our present knowledge. 



