CHAPTER 2 



THE KINETICS OF ENZYME REACTIONS 



An enzyme reaction occurs on the surface of a protein molecule, at a re- 

 gion where the arrangement of the polypeptide chains has placed particular 

 groups in such a pattern that the substrate molecule is not only bound but 

 altered in a manner conducive to reaction. This reaction may be intramole- 

 cular or, more commonly, with another molecule also bound to the enzyme, 

 to form a new substance or substances. Groups other than of polypeptide 

 origin and bound to the protein may, of course, participate in the catalysis 

 in certain instances. The fundamental process is the formation of temporary 

 complexes of the reacting molecules with the protein or its accessory groups 

 at a special region or active center. One is interested in these complexes and 

 the nature of the active center in inhibition studies because most enzyme 

 inhibitors interfere with the formation or breakdown of such complexes by 

 combining either with the active center directly or with adjacent regions 

 of the enzyme. The over-all reaction catalyzed by a simple enzyme is made 

 up of at least three phases: (a) the formation of the appropriate complex 

 or complexes of enzyme and reactants, (b) the intermolecular rearrangements 

 to form complexes of the enzyme and the products, and (c) the dissociation 

 of these complexes to form the free enzyme and the products of the reaction. 

 The rate at which the products are formed thus might depend on the rate of 

 any one of these phases, if it is much slower than the others, or on any 

 combination of the rates if they are of comparable magnitude; it may also 

 depend on the rate at which the enzyme-substrate complex dissociates to 

 form the original substrate and the free enzyme. The presence of an inhibitor 

 modifies these rates so that a reduction in the formation of products results. 

 A study of inhibition ideally involves a quantitative formulation of the 

 rate changes so that some insight may be obtained into the mechanism. 

 These quantitative aspects of inhibition are extensions of the general enzyme 

 kinetics and thus it is necessary in this chapter to consider the basic con- 

 cepts and formulations of enzyme catalysis. It will be particularly impor- 

 tant to examine critically the interpretation of the mathematical expres- 

 sions with regard to the actual molecular events occurring, inasmuch as true 

 understanding implies at least a partial visual interpretation of the pro- 

 cess. The excellent books of Dixon and Webb (1958) and Laidler (1958) 



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