CELLULAR METABOLISM 



107 



this complex formation awaits clarification of the structure of proteins, 

 since it is probably the protein moiety which combines with the sub- 

 strate. The substrate to be oxidized must fit quite closely to the side 

 chains of the protein molecule where combination occurs. No lock, how- 

 ever, remains immune to the prying of false keys ; and substances with 

 chemical structure close to that of the substrate will compete for union 

 with the protein, thus affecting the activity of the enzyme. This is 

 strikingly demonstrated by the inhibition of acetate oxidation by fluoro- 

 acetate discovered in animal tissues (Bartlett, Ahrens, and Barron 

 [14]) and in yeast (Kalnitsky and Barron [42]). In yeast, acetate 

 oxidation, completely inhibited by monofluoroacetate, was not affected 

 at all by the other halogen acids, bromo-, iodo-, chloro- acetic acids, as 

 well as by trifluoroacetic acid (Table I). This inhibition is due to compe- 



TABLE I 



Effect of Halogen Acetates on the Oxidation of Acetate by Baker's Yeast. 



pH, 6.2, Temp. 25°. Acetate concentration, o.oi M ; halogen acetate, o.ooi 



M. 



tition of fluoroacetate with acetate in the protein of the enzyme, for 

 inhibition occurs in the first step of acetate metabolism, namely citric 

 acid formation (Table II). Of all these acids it is monofluoroacetic acid 

 which approaches most closely in size acetic acid, as the interatomic 

 distance between C and F (1.41 A) is only 0.32 A more than the inter- 

 atomic distance between C and H. An increase in the interatomic distance 

 of 0.35 A as in C and CI (1.76 A) was enough to avoid penetration of 

 the halogen acid into the space reserved for acetic acid in the protein 



