272 ENZYMES 



Specificity 



In the study of digestion (Chap. 12) it is noted that fat-splitting en- 

 zymes are without effect on carbohydrates or proteins. Neither does an 

 enzyme that hydrolyzes one of the latter attack fats. Even the common 

 disaccharides require different enzymes to effect their hydrolysis. Spe- 

 cificity is frequently due to type of linkage rather than to individual 

 compounds, as is evidenced by the fact that trypsin digests various pro- 

 teins that differ markedly in composition and size of molecule. Further- 

 more, emulsin, which causes hydrolysis of many ^-glucosides, has no 

 effect on the isomeric a-glucosides ; the reverse is true of maltase. 



Inhibition 



Enzymes are inhibited by a variety of conditions, which have already 

 been indicated under factors affecting activity. In the present discussion 

 attention is focused on the types of inhibition that can be obtained with 

 chemical reagents. There are two main types: competitive and noncom- 

 petitive. If, for example, succinic dehydrogenase is inhibited by malonate 

 {i.e., a soluble salt of malonic acid) , a substance which is similar in struc- 

 ture to succinate (the normal substrate of this enzyme), the inhibition 

 can be competitively reversed by increasing the substrate concentration. 

 This means that the amount of inhibition produced depends primarily 

 on the relative amounts of malonate and succinate present. On the 

 other hand, if this enzyme is inhibited by quinone, for example, the 

 activity cannot be restored by an increase in succinate concentration. 

 This is termed noncompetitive inhibition. These phenomena can be 

 visualized if one considers that the enzyme surface has specific points of 

 attachment which fit snugly against groups of the substrate molecule. 

 If an inhibitor is used that is so similar in structure to the substrate that 

 it also can fit into the "mold" on the enzyme surface, it can compete 

 with the substrate for position. However, if an agent is used that changes 

 the enzyme in some way, the substrate can no longer attach to the surface 

 regardless of the amount used. The relation between substrate and in- 

 hibitor then becomes noncompetitive. 



Various inhibitors have been used successfully for the study of met- 

 abolic reactions. If it is desired to study the conversion of a-keto- 

 glutarate to succinate in the presence of other enzymes of the Krebs cycle 

 (see Chap. 13) , one can prevent the further metabolism of succinate by 

 the addition of malonate. For additional examples concerned with vita- 

 mins, see p. 256. 



Some drugs are known to exert their action by inhibition of enzymes. 

 For example, eserine, an alkaloid (C15H21N3O2) that stimulates the 

 parasympathetic nervous system, inhibits the enzyme choline esterase 



