310 



6. INTERACTIONS OF INHIBITOES WITH ENZYMES 



marked dependence of catalytic activity upon the spatial configuration 

 and the effects of various groups on the strength of binding, but also show 

 that the effect of a certain group on the energy of interaction varies with 

 its orientation with respect to the rest of the molecule. For example, 

 introducing three fluorine atoms into the acetyl group of or-iV-acetyltyro- 

 sinamide increases somewhat the affinity of the enzyme for the L-isomer 

 substrate but decreases the affinity for the D-isomer inhibitor. In estab- 

 lishing the effects of such group alterations one must thus take the total 

 configuration into account. 



%inh 



Fig. 6-21. Inhibition of amine oxidases by diamidines as influenced by 

 the number of — CHj — groups in the inhibitor. (From Blaschko and 

 Himms, 1955.) Ciu've 1: guinea pig hver, tyi-amine. (I) = 1 mM; curve 

 2: pig liver, tyramine, (I) = 0.2 mM; curve 3: cat liver, tyramine, 

 (I) = 0.2 mM; curve 4: ox serum, spermine, (I) = 0.005 mil/. 



{(l) Effect of group cJianges on type of action. When simple group additions 

 or replacements are made in an inhibitor, it may not be certain that the 

 observed change in inhibition is due to an altered effect on a single en- 

 zyme system. Determination of the res]uratory inhibition produced by 

 the halogen-acetates illustrates this well. The change in inhibition charac- 

 teristics when a fluorine atom replaces an iodine or bromine atom might 



