148 1. MALONATE 



So far we have considered total fatty acid synthesis. Separation of the 

 different fatty acids from animal tissues in malonate experiments has not 

 been done, but in mycobacteria malonate shifts the incorporation of acetate 

 into the higher fatty acids (Kusunose et al., 1960). The synthesis of total 

 fatty acid is moderately increased and this was attributed to the formation 

 of malonyl-CoA (see accompanying tabulation). Differential effects of mal- 



Acetate-l-C* incorporation 



Fatty acid % Change 



Control Malonate 3.3 mM 



Palmitate 7627 



Stearate 2887 



Arachidate 1144 



Behenate 1089 



Lignocerate 1862 



Total acids 14609 17234 + 18 



onate on the synthesis of short-chain and long-chain fatty acids are also 

 seen in rat liver slices metabolizing octanoate-1-C^* (Lyon and Geyer, 1954). 

 Although the over all effect of malonate on lipid synthesis in a particulate 

 preparation from avocado mesocarp is not marked, the incorporation of 

 acetate is shifted from stearate to oleate (see accompanying tabulation) 



(Mudd and Stumpf, 1961). Although malonate may inhibit the cycle, this 

 may be counteracted by the formation of malonyl-CoA, which dilutes the 

 labeled malonyl-CoA formed from labeled acetate. It is interesting that 

 malonate is formed from acetate in avocado and this may be one regulatory 

 factor in fatty acid synthesis. Malonate has been found in three instances 

 to exert only inhibitory effects on fatty acid synthesis: in cell-free prepara- 

 tions from pigeon liver, 20 mM malonate inhibits the incorporation of 

 acetate into fatty acids 32% (Brady and Gurin, 1952); in various tumor 

 tissues (mammary and testicular carcinomata, and a sarcomatoid ovarian 



