EFFECTS OF MALONATE ON LIPID METABOLISM 



143 



Table 1-25 



Effects of 5 mM Malonate on the Oxidation of Fatty Acids in Rat Liver 



Slices " 



" Slices incubated 1 hr with carboxyl-labeled fatty acids shown in Table 1-24 at 

 38° and pH 7.1. The data from the five fatty acids were averaged to indicate the 

 general effects of malonate. (From Geyer et al., 1950 b.) 



CO— fragments are believed to enter the cycle. The CHgC^* o_/— CHaC^^ 

 00" ratio in acetoacetate will depend on the rates of production and utili- 

 zation of these two fragments. As pointed out, these two types of 2-carbon 

 fragment may be only convenient designations for two reactive forms of 

 acetyl-CoA. Malonate is assumed to increase the formation of acetoacetate 

 by condensation of randomized fragments of the — CHaC^^O — type, so 

 that the ratio rises. The extra acetoacetate formed over the control when 

 malonate is present does indeed exhibit a ratio of unity for hexanoate and 

 octanoate oxidation (Geyer et al., 1950 b). If malonate does this by blocking 

 the cycle, a preferential accumulation of — CH2CO — fragments would occur, 

 and a greater proportion of the acetoacetate would be formed from them. 

 The effect of malonate on acetoacetate accumulation will depend on the 

 pathway of fatty acid oxidation in the uninhibited tissue and, hence, on the 

 experimental conditions. For example, Witter et al. (1950) found that 3 mM 

 malonate inhibits acetoacetate formation from hexanoate 4% and 10 mM 

 malonate inhibits 9% in suspensions of washed particles from rat liver. 

 However, hexanoate is quantitatively converted to acetoacetate in the con- 

 trols, presumably because no cycle intermediates, are present to form oxal- 

 acetate for condensation of the acetyl-CoA units. Under such circumstances 

 malonate would not be expected to increase acetoacetate and the small 

 inhibitions must be attributed to actions directly on the helix. The rela- 

 tionship between acetoacetate formation in malonate-inhibited systems 

 and the presence of cycle intermediates was illustrated and discussed by 

 Cheldelin and Beinert (1952). 



