230 



1. MALONATE 



Pathways of Malonate Metabolism in Microorganisms 



An analysis of the pathways of malonate oxidation was made simultane- 

 ously in the laboratories of Hayaishi and Rittenberg between 1953 and 1955. 

 The work was done on Pseudomonas fluorescens, a soil isolate capable of 

 utilizing malonate as the sole carbon source, and adapted to malonate by 

 culture in 27-33 nvM malonate media. Hayaishi (1953) observed that the 

 decarboxylation of malonate requires ATP and CoA and postulated that 

 malonate must first be activated, probably to malonyl-CoA. Using partially 

 purified extracts from Pseudomonas, it was shown that malonate is quanti- 

 tatively converted to COg and acetate, no other products being detectable 

 chromatographically. The proposed scheme (1-7) may be represented as 

 follows (Hayaishi, 1954, 1955 a): 



Malonate 



Acetate 



Malonate 



(1-7) 



Acetyl — CoA 



The cyclic process thus involves the transfer of CoA back and forth be- 

 tween the acetyl and malonyl groups. Wolfe et at. (1954) also ruled out the 

 direct decarboxylation to acetate by showing a dependence on ATP and 

 CoA, and in later work (Wolfe et al., 1954 b, 1955; Wolfe and Rittenberg, 

 1954) proposed the following scheme (1-8) based mainly on chromatographic 

 analyses of intermediates and products: 



Acetate + Malonyl-diCoA- 



Malonate 



ATP + CoA 



t 

 Malonyl - CoA 



Acetyl - CoA 



>■ 



(1-8) 



The principal difference between the two schemes is the participation of 

 malonyl-diCoA. Hayaishi's results do not exlude it but provide no evidence 

 for it, while Wolfe et al. claim to have detected it chromatographically. 

 Although the decarboxylation of malonate is characterized by AF = — 7 

 kcal/mole, the activation energy is presumably so high that the more com- 

 plex mechanisms above are necessary. The malonate decarboxylase and 



