374 2. ANALOGS OF ENZYME REACTION COMPONENTS 



parent compounds; both facts indicate the importance of polarization of 

 the inhibitor molecule in the field of ionic groups on the enzyme. The ac- 

 tive site has a locus for interaction with the aromatic nucleus, and vicinal 

 to this there is at least one anionic group; the orientation of the inhibitor 

 is determined by the interaction of the polarizable group with a sublocus. 

 Molecules presenting a larger planar area are more inhibitory, and it seems 

 that the site at which the aromatic compounds act is mainly flat, of greater 

 length than breadth, and not straight but curved along the enzyme surface. 

 The different loci involved in the interactions perhaps have different prop- 

 erties; e. g., it was postulated that the active site may be hermaphroditic* 

 in that one locus may be electron-deficient and another electron-rich. 



The chymotrypsin reaction proceeds in two steps, the acetylation of the 

 enzyme: 



EH + AcB z^ (EH— AcB) ^ (EAc-HB) ^ EAc + HB 



and the solvolysis of the acetylchymotrypsin: 



EAc + HOR ^ (EAc-HOR) ^ (EH— AcOR) 5=t EH + AcOR 



The competitive inhibitors tabulated here were shown by Foster (1961) 

 to block the acetylation reaction and not the solvolysis. The inhibition by 

 indole is not strictly competitive (Applewhite et al., 1958). 



The relation of chymotrypsin or a chymotrypsin-like enzyme to hista- 

 mine release and the anaphylactic reaction was examined by Austen and 

 Brocklehurst (1960) in guinea pig lung sensitized to ovalbumin. Inhibitors 

 such as /5-phenylpropionate, indoleacetate, and indolepropionate depress 

 anaphylactic histamine release more than 50% at 2.5 mM, and indole and 

 skatole are effective at 1 mM or below. Antigen apparently activates some 

 proteolytic enzyme necessary for the release of histamine. 



* This terminology connotes an entirely new way of looking at enzyme catalysis. 



