154 



1. MALONATE 



Control 



Malonate 20 mM 



that malonate is converted to oxalosuccinate via malonyl-CoA. The oxalo- 

 succinate might function in the NAD- and NADP-dependent isocitrate 

 dehydrogenase systems to form a transhydrogenase so that NADPH is 

 the eventual donor for the formation of glutamate, oxalosuccinate acting 

 catalytically. Such studies show how complex the effects of malonate on 

 amino acid metabolism can be. The oxidation of certain amino acids pro- 

 ceeds via an initial transamination followed by degradation of the deaminat- 

 ed acids. The oxidation of y-aminobutyrate is completely inhibited by 

 1 n\M malonate in rat brain mitochondria (Sacktor et al., 1959) but in 

 Bacillus pvmilus is not affected even by 40 mM malonate (Tsunoda and 

 Shiio, 1959). Whether the former inhibition is the result of an indirect 

 suppression of transamination by cycle block or a direct effect on the oxi- 

 dative pathway of this amino acid is not known. 



iV-Acetylaspartate occurs at a relatively high concentration in mamma- 

 lian and avian brain, increasing rapidly after birth. Its formation involves 

 direct acetylation of aspartate and the brain has little ability to metabolize 

 this substance. When acetate-1-C^* is injected intracerebrally, some of the 

 C^* is later found in A^-acetylaspartate (Jacobson, 1959). The injection of 

 malonate with the acetate reduces the incorporation of the C^* about 50%. 

 The injection of acetate depresses the level of total A^-acetylaspartate and 

 malonate counteracts this. These effects are quite complex and difficult to 

 interpret. The concentration of malonate injected was high (1.34 M) and 

 could have caused a severe fall in ATP so that acetate activation prior to 

 acetylation would be depressed. The rise in ^V-acetylaspartate seen with 

 malonate might have been due to a cycle block counteracting the effect 

 of the injected acetate, whereby cycle intermediates involved in trans- 

 aminations would be decreased, the level of aspartate being maintained with 

 more aspartate available for acetylation. There are so many pathways 

 associated with aspartate metabolism and acetylation reactions that the 

 final effects of a cycle block are difficult to predict. A good example of the 

 complex effects of malonate on amino acid metabolism is seen in Table 

 1-19, where certain types of amino acid in potato slices increase and other 

 types decrease during incubation with malonate (Romberger and Norton, 

 19C1). 



