334 2. ANALOGS OF ENZYME REACTION COMPONENTS 



Glutamate Transaminases 



This enzyme apparently possesses two cationic groups properly separated 

 to interact with glutamate and the other dicarboxylates, because it is inhib- 

 ited best by glutarate of all the saturated dicarboxylates, as shown in the 

 accompanying tabulation (aspartate =1.7 mM and a-ketoglutarate = 6.7 

 mM) (Jenkins et al., 1959). This is one instance in which the «-methyl 

 analog has no affinity for the enzyme. Very similar results were obtained 



Inhibitor (40 mM) 



Malonate 



Succinate 



Glutarate 



Adipate 



Piraelate 



Suberate 



Maleate 



a-Methylaspartate 



a-Methylglutaniate 



by Velick and Vavra (1962), glutarate inhibiting the most potently of the 

 saturated dicarboxylates; from their values for K, one can calculate that 

 glutarate is bound 0.85 kcal/mole more tightly than succinate, and 0.32 

 kcal/mole more tightly than adipate. Of the three phthalates, o-phthalate 

 is the most inhibitory {K^ = 5 mM), m-phthalate intermediary (K^ = 8 

 mM), and j^-phthalate the least active {K, = 10 mM). The results of the 

 studies above were obtained on pig heart transaminase, and from the lim- 

 ited data reported by Goldstone and Adams (1962) it would appear that 

 the enzyme from rat liver is different in that glutarate is about 10 times 

 more potent than maleate as an inhibitor. The alanine:a-ketoglutarate 

 transaminase from rat liver is inhibited moderately and competitively by 

 certain amino acids, such as leucine and valine, and also by maleate, but 

 no data were given for comparison with the aspartate: a-ketoglutarate trans- 

 aminase (Segal et al., 1962). Fluorooxalacetate inhibits the latter enzyme 

 from heart competitively with respect to oxalacetate (and to a-ketoglutarate 

 and aspartate when the reverse reaction is run), K^,, being 3.5mMforof- 

 ketoglutarate and 0.5 mM for aspartate, and /f, being 0.1 mM (Kun et 

 al., 1960). It is also slowly transaminated to fluoroaspartate which likewise 

 inhibits the enzyme. 



