146 GENERAL BIOCHEMISTRY 



Non-competiiive inhibition occurs when addition of substrate does 

 not reverse the effect of tlie iniiibitor even tiiougli tire reaction of 

 inhibitor and enzyme is reversible. There are at least two mechanisms 

 by which this situation can arise. First, 



E + I ^ EI 



EI + S ±^ SEI 



Here the inhibitor combines with the enzyme at some point other 

 than the enzymatically active site, allowing the substrate to take its 

 normal position. However, the inhibitor exerts at a distance enough 

 influence to block the formation of products. The addition of more 

 substrate has little effect on the rate, and there is no competition 

 between enzyme and inhibitor. 



Another type of non-competitive inhibition occurs when the in- 

 hibitor reacts with the enzyme-substrate complex 



ES + I ±1; ESI 



to prevent the formation of products. Again the increase in substrate 

 concentration has little effect on the catalytic rate in the presence of 

 the inhibitor. Finally, inhibition can occur when 



S + I ^ SI 



and this equilibrium also leads to the non-competitive type. 



Much work on enzyme inhibition has been carried on merely as a 

 study of the nature of the phenomenon. But in the process something 

 has been learned about the nature of the reactive sites of certain 

 enzymes. In addition, there is much practical interest in such studies 

 because many of the antibiotics are thought to be enzyme inhibitors. 

 This medically important class blocks key enzyme reactions in patho- 

 genic organisms when administered in doses too small to be harmful 

 to the animal concerned. 



A few effective inhibitors for enzymes have turned out to be proteins 

 themselves. A protein from soybean prevents the proteolytic action 

 of trypsin and is thus called trypsin inhibitor. Although trypsin 

 normally catalyzes the hydrolysis of proteins, it does not attack this 

 one, probably because the inhibitor possesses no exposed peptide bonds 

 of the types susceptible to trypsin. The inhibitor and enzyme do, 

 however, form a stable complex preventing the enzyme from combin- 

 ing with molecules of substrate protein. 



