458 



2. ANALOGS OF ENZYME REACTION COMPONENTS 



p-aminophenylalanine act similarly, but anionic polyalanine, poly aspartate, 

 and polyglutamate do not inhibit, indicating purely electrostatic binding. 

 The inhibition disappears at high poly-L-lysine concentrations (Dellert and 

 Stahmann, 1955). Changes in the optical transmittance also occur (Fig. 2- 

 15); that is, low concentrations of inhibitor complex with the enzyme to 

 decrease the solubility, but as the inhibitor concentration rises the com- 



FiG. 2-15. Inhibition of pepsin by polylysine of mean molecular weight 2100 

 at pH 4.7. Transmittance determined at 400 m//. (Data from Dellert and 



Stahmann, 1955.) 



plexes become more soluble. However, the correlation between inhibition 

 and transmittance is such as to suggest that the depression of enzyme ac- 

 tivity is by no means directly related to the aggregate size of the complex. 

 Some have believed that pepsin plays a role in the genesis or maintenance 

 of gastric ulcers and hence have looked for inhibitors that might be affective 

 clinically. Strange to say, they have invariably used macroanions such as 

 heparin, chondroitin sulfate, polyhydromannuronic sulfate, and various pol- 

 ymers formed by condensation of aldehydes with hydroquinonesulfonate 

 (Levey and Sheinfeld, 1954; Marini and Levey, 1955; Heymann et al., 1959). 

 The isoelectric point of pepsin is around 2.8 so the relative effectiveness of 

 macroanions and macrocations might depend on the experimental or phys- 

 iological pH. Although the hydrolysis of casein is inhibited to some extent 

 by these polymers, it is possible that this is due in part or wholly to the 

 formation of complexes with the casein. It has been claimed that chon- 

 droitin sulfate and the polymeric sulfonates reduce the number of ulcers 

 in Shay rats, but it is doubtful if this is related to pepsin inhibition, even 

 if it occurs, and there are other explanations (for example, inhibition of 

 lysozyme, which has also been implicated in ulceration). 



