ANTIBODY AS A SPECIFIC EIS^ZYME INHIBITOR 161 



duced. This structural relationship between the substrate and the 

 inhibitor is the reason for the affinity an inhibitor possesses for the 

 enzyme, and thereby causes the inhibition of the enzyme. In the follow- 

 ing pages the formation of several such specific enzyme inhibitors will 

 be considered. 



1. Pepsin Inhibitor 



It has been shown by Herriott (1938, 1941) that pepsinogen auto- 

 catalytically is transformed into pepsin at pH 4.6; the pepsin formed 

 catalyzes the reaction. During this transformation there are simultane- 

 ously produced certain polypeptides one of which has a powerful 

 inhibiting action on pepsin at pH 5.0-6.0. The inhibitor has been 

 isolated in the form of spheroids which change later on to rosettes of 

 tiny needles. This inhibitor on combining with pepsin between pH 

 5.0 and 6.0 forms a dissociable inhihitor-fe-psin complex. The reversible 

 combination of pepsin vdth the inhibitor follows quantitatively the 

 simple mass law equation. 



The molecular weight of the inhibitor as determined by diffusion 

 and combining equivalence with pepsin lies somewhere between 4000 

 and 10,000. Since 0.000,25 mg. of inhibitor nitrogen is approximately 

 equivalent to 0.0012 mg. of pepsin nitrogen in the inhibitor-pepsin 

 complex the ratio of mg. of inhibitor N to mg. of pepsin N is 1 :4.8, 

 or one molecule of pepsin reacts wdth one molecule of inhibitor. 



This complex dissociates upon dilution and upon acidification (in 

 a manner which appears to be comparable to the dissociation of anti- 

 gen-antibody complex under the same conditions). It does not combine 

 in acid solution. The entire reaction is presented by Herriott as follows: 



Pepsin pH<5.4 Pepsin 



Pepsinogen > Pepsin-Inhibitor < > -f- 



Compound pH>5.4 Inhibitor— >X 



The first reaction from pepsinogen to pepsin-inhibitor compound 

 is catalyzed by pepsin, while the second reaction from the compound 

 to free pepsin and the inhibitor is a reversible dissociation. The third 

 reaction is the destruction of the inhibitor on long standing with pepsin 

 between pH 2.0 and 5.0. 



The pepsin inhibitor is a polypeptide which has basic groups which 

 are exposed, since it is precipitated by many reagents used to precipi- 



