348 2. ANALOGS OF ENZYME REACTION COMPONENTS 



K^ (mi/) 



Inhibitor 



Benzoate 



Salicylate 



^-Aminosalicylate 



p-Arainobenzoate 



p-Nitrobenzoate 



Aniline 



Phenol 



m-Aminophenol 



p-Nitrophenol 



2,4-Dinitrophenol 



2,6-Dinitrophenol 



2,4,6-Trinitrophenol — 0.64 0.012 



crystallized the complex of apoenzyme, FAD, and benzoate, and found 

 equimolar amounts of each component present. 



It would be interesting to have more data on the effects of these inhibitors 

 on L-amino acid oxidases. Benzoate inhibits the L-amino acid oxidases 

 from rat kidney (Blanchard et al., 1944) and snake venom (Zeller and Maritz, 

 1945), but does not inhibit the enzyme from Neurospora even at 10 niM 

 (Burton, 1951 b). 



Benzoate on Other Enzymes and Metabolism 



The endogenous ammonia formation and respiration of rat kidney slices 

 are inhibited 52% and 66%, respectively, by 25 mM benzoate (Herner, 

 1944). One might assume that the former might be attributed to inhibition 

 of amino acid oxidases, but this is unlikely because benzamide, phenyl- 

 acetate, and /?-phenylpropionate are even more potent inhibitors than 

 benzoate. The deamination of various l- and D-amino acids in kidney is, 

 however, strongly inhibited by benzoate, at least in part competitively. 



The inhibition of respiration by benzoate was first observed by Grif- 

 fith (1937) in slices and minces of various tissues in the presence of glucose, 

 but no analysis of the site of action has been published, although in con- 

 nection with recent studies on the salicylates some effects on mitochondria 

 have been investigated. Benzoate inhibits the oxidations of citrate, a- 

 ketoglutarate, and succinate in rat kidney homogenates but is invariably 

 less active than salicylate (E. H. Kaplan et al., 1954); and neither the Og 

 uptake nor the P : ratio is affected markedly in rat liver mitochondria, 

 although salicylate uncouples strongly (Brody, 1956). Endogenous phosphor- 



