METABOLISM OF MALEATE 311 



Porphyrin Synthesis 



Fiimarate at 10 mM augments porphyrin synthesis in chicken erythro- 

 cytes incubated with 70 mM glycine, but 10 mM maleate inhibits 88% 

 (Granick, 1958). Since an active cycle is required for the formation of 

 succinyl-CoA to condense with glycine in the initial step of porphyrin syn- 

 thesis, one might immediately surmise that the inhibition is possibly on 

 a-ketoglutarate oxidase. The synthesis of (5-aminolevulinate by guinea pig 

 liver mitochondria incubated with glycine and citrate is inhibited 44% by 

 10 mM maleate (Granick and Urata, 1963), so that a definite effect on 

 the early stages of synthesis is clear. However, the exact site for the in- 

 hibition is not clear. Granick and Urata suggested cis-aconitase as the 

 sensitive enzyme, but I know of no direct evidence that this enzyme is 

 affected by maleate (see Table 2-2). Inasmuch as maleate at 10 mM would 

 certainly inhibit a-ketoglutarate oxidase to some extent, even in liver, 

 during a 2 hr incubation, this might also be considered as the site of action. 

 The (5-aminolevulinate synthetase itself may well be susceptible to maleate 

 but has not been tested directly. 



Cysteine Metabolism in Entamoeba and E. Coli 



The formation of RgS and COg from glucose and cysteine under anaerobic 

 conditions by Entamoeba histolytica, probably an important pathway in 

 this organism, involves the formation of a labile sulfur compound (possibly 

 /5-thiopyruvate) by reaction of cysteine with pyruvate, the release of HgS 

 from this intermediate, and the reduction of the cystine formed by 3-phos- 

 phoglyceraldehyde to restore the cysteine. The formation of HgS is inhib- 

 ited 46% and of COg 14% by 20 mM maleate (Kun et al, 1955). Although 

 a number of enzymes participate in this system, possibly maleate reacts 

 directly with cysteine or /?-thiopyruvate, the production of HgS being af- 

 fected more than the release of COj. In E. coli, cysteine is metabolized to 

 H2S and ammonia, and Tamiya (1954) postulated an oxidative deamination 

 involving /?-thiopyruvate as an intermediate. Maleate at 5 mM has no ef- 

 fect on this pathway. Although the concentration here is less than in the 

 work with Entamoeba, the results make it less likely that maleate reacts 

 with cysteine or /^-thiopyruvate with sufficient rapidity to account for the 

 former inhibition. 



METABOLISM OF MALEATE 



The possible utilization of maleate has always been a complicating factor 

 in studying metabolic inhibition by this substance in tissues. Much work 

 has shown that fumarate can be readily utilized, whereas maleate generally 

 is not, although definite metabolism of maleate has been demonstrated in 



