INHIBITORS STRUCTURALLY RELATED TO MALONATE 235 



a novel reaction was discovered, namely, the interconversion of methyl- 

 malonate and succinate. The enzyme, which has been called a methyl- 

 malonyl-CoA isomerase, catalyzes the reaction: 



Methylmalonyl-CoA :^ succinyl-CoA 



and has been purified from ox liver (Stern and Freidman, 1960) and Pro- 

 fionihacterium shermanii (Wood and Stjernhohn, 1961; Stjernholm and 

 Wood, 1961). At equilibrium the ratio (succinyl-CoA)/(methylmalonyl-CoA) 

 is 10.5 (pH 7 and 25°). This reaction functions in both the oxidation and 

 formation of propionate. Another reaction of importance in propionate 

 metabolism is 



Methylmalonyl-CoA + pyruvate :^ propionyl-CoA + oxalacetate 



It is catalyzed by methylmalonyl-oxalacetate transcarboxylase, whereby a 

 carboxylation may be effected without the intervention of COg or the ex- 

 penditure of energy to activate COg. It may finally be noted that the feed- 

 ing of malonate to dogs leads to a marked excretion of methylmalonate in 

 the urine (Thomas and Stalder, 1958). This does not necessarily mean that 

 the methylmalonate is formed from malonate, since malonate inhibits the 

 interconversion of methylmalonyl-CoA and succinyl-CoA very strongly 

 (Flavin et al., 1955). 



INHIBITORS STRUCTURALLY RELATED TO MALONATE 



The inhibition of succinate dehydrogenase by various dicarboxylate ions 

 was treated earlier (page 34). Maleate will be dealt with in Chapter III-2 

 and oxalate will be discussed in Volume IV. Inhibitors related to malonate 

 will also be found in the following chapter on analogs. It then remains to 

 take up the esters of malonate, hydroxy malonate, and those compounds 

 in which the carboxylate groups have been replaced by other anionic groups. 

 As mentioned previously, there is often confusion in the nomenclature; we 

 shall adopt the following (using the ethyl derivatives as examples): 



COO" Et^ /COO" 



Et— Hc:" . /C^ _ 



coo Et COO 



Ethylmalonate Diethylmalonate 



/COO /COO— Et 



HgC Hz^s, 



^COO— Et ^COO — Et 



Malonic Malonic 



monoethyl ester diethyl ester 



