3. KINETICS OF ENZYME INHIBITION 51 



C. Generalized adsorption onto the protein surface: a relatively nonspe- 

 cific and weak interaction by substances, frequently nonpolar or 

 amphotropic compounds, that associate with the protein side-chains 

 and may interfere with binding of any component. 



D. Denaturation of the protein: an alteration of the basic protein struc- 

 ture, usually by substances reacting with those protein groups re- 

 sponsible for the bonds holding the polypeptide fabric in a specific 

 orientation. 



E. Hydrolysis of apoenzyme: the breaking of peptide bonds in the pro- 

 tein, generally by proteolytic enzymes, giving rise to fragments of 

 the apoenzyme that may be partially or completely inactive. 



(II) Reaction of inhibitor with substrate: the binding or the subsequent trans- 

 formations of the substrate are hindered. 



(III) Reaction of inhibitor with coenzyme: generally the ability of the coen- 

 zyme to participate in the reaction is reduced, although the affinity for 

 the apoenzyme may also be decreased. 



(IV) Reaction of inhibitor ivith activator 



(V) Reaction of inhibitor with enzyme-complex: combination with the enzyme- 

 substrate, enzyme-coenzyme, or enzyme-activator complex, although 

 there is not necessarily a reaction with any of the individual components. 



(VI) Entry of inhibitor into the reaction sequence: the inhibitor may be acted 

 upon by the enzyme so that it undergoes reactions similar to the sub- 

 strate, this reducing the amount of substrate reacted or causing a sub- 

 sequent block if a normal transfer reaction is slowed. 



(VII) Reaction of inhibitor with linking components in an enzyme aggregate: 

 dissociation of enzyme units in a complex system by interaction with 

 substances, perhaps nonprotein in nature, functioning structurally in 

 the spatial orientation of these units. 



It may be noted that the words reaction and interaction as used here and 

 elsewhere in this book do not imply any particular type of relationship 

 between the molecules involved nor limit the forces that are operative. The 

 reaction of an inhibitor with the sites and substances outlined above may 

 be chemical in the sense that electron pair bonds are formed but it is gen- 

 erally not and the term reaction should not be construed as indicating such 

 a chemical reaction. When two molecules enter into a relationship in which 

 their mutual energy levels are altered, these molecules are said to react or 

 interact; whether the relationship is one of greater or less stability depends 

 on the direction of the energy change. The nature of the forces involved 

 will be discussed in Chapter 6; we wish now only to emphasize that no 

 specific forces are implied by the general terms used. 



Visualization at the molecular level of the different types of inhibitor 

 reactions at the enzyme surface is often helpful in distinguishing between 



