232 1. MALONATE 



of malonyl-CoA has been found in Clostridium kluyveri (Vagelos, 1960). 

 In bush bean {Phaseolus vulgaris) leaves, incubation with malonate-2-C^* 

 leads to labeled citrate, isocitrate, and malate, indicating a pathway through 

 acetyl-CoA and the cycle (Young and Shannon, 1959). Malonate is incor- 

 porated in isolated spinach chloroplasts at about half the rate for acetate, 

 much of the label appearing in lipids (Mudd and McManus, 1964). 



Metabolism of malonate was first described in the dog by Pohl (1896), 

 who found that only a fraction of the malonate administered to the animals 

 can be recovered in the urine. This subject was not taken up again until 

 1950 and since that time much has been learned of how the body deals 

 with malonate, and of the role of malonate and its derivatives in normal 

 metabolism. It would appear from the limited data that about 30% of 

 the administered malonate is metabolized (Lifson and Stolen, 1950; Busch 

 and Potter, 1952 a). However, the rate of oxidation is relatively slow and 

 in rabbits represents less than 2% of the total respiration (Wick et al., 

 1956). The rate of oxidation may be in part limited by the transfer from 

 the extracellular space into the tissues, since this is slow. 



Various mammalian tissues can decarboxylate malonate and utilize the 

 acetate formed. This has been investigated most completely in rat tissue 

 slices by Nakada et al. (1957), who determined the 0^*0, arising from mal- 

 onate-1-C^^ during 1 hr incubation at pH 7.4, the total concentration of 

 malonate being 5 xnM (see accompanying tabulation). Kidney, liver, and 



Tissue Added C^* as Qi^Oa (%) 



Kidney 27.0 



Liver 18.0 



Heart 15.2 



Diaphragm 6 . 8 



Spleen 1 . 7 



Brain 1 . 5 



Lung 1 . 



Testis 0.6 



heart are particularly active, and the tissues show a wide range of decar- 

 boxylative ability, part of which may be due to different rates of penetra- 

 tion. The variation of malonate oxidation with concentration is shown in 

 Fig. 1-22 for rat kidney slices, and an inhibition of its own metabolism is 

 seen at concentrations above 5 vaM. The inhibition of acetate- 1-C^* oxida- 

 tion is shown for comparison. The relative rates of activation of malonate, 

 succinate, and glutarate by several tissues were determined by measuring 

 the rates of formation of hydroxamic acid from hydroxylamine during the 



