ANALOGS WHICH ARE ISOMERS OF SUBSTRATES 271 



this is apparent only and the type of inhibition does not fit into the usual 

 classical categories. The following scheme was proposed: 



E + PS ^ EPS :^ EP + S 



E + P 



where PS is phosphoserine. It was shown to fit the data kinetically if 

 k_Jki is small. This example shows well the danger of uncritically accepting 

 the usual interpretation of a plotting procedure since, as emphasized 

 previously, there are types of inhibition different from those included 

 in the classic formulations. 



a-Chymotrypsin hydrolyzes the L-isomers of various tryptophanamides 

 and tyrosinamides, and these reactions are usually inhibited by the D-iso- 

 mers (Huang and Niemann, 1952; Manning and Niemann, 1958). When 

 the substrate is nicotinyl-L-tryptophanamide (Kg = 2.7 mM), the reaction 

 is inhibited by nicotinyl-D-tryptophanamide (K^ =1.4 mM) and a number 

 of other derivatives of D-tryptophanamide. The hydrolysis of several de- 

 rivatives of L-tyrosinamide is similarly inhibited by the D-isomers (see ac- 

 companying tabulation). It is to be noted that in every case the D-isomer 

 is bound more tightly than the L-isomer, assuming that K^ does indeed 

 represent a dissociation constant. The possible forces binding these sub- 

 stances to the enzyme will be discussed in a later section (pages 370-375). 



Tyrosinamide Kg for L-isomer K^ for D-isomer 



Anomeric Analogs 



Michaelis and Pechstein (1914), in their early work on /5-fructofuranosi- 

 dase, and Michaelis and Rona (1914), studying yeast maltase inhibition, 

 concluded that the configuration around carbon 1 of carbohydrates (i.e., 

 a- and /5-anomers) is of importance in determining the affinity of these 

 substances for the enzymes, since a-methylglucoside inhibits both enzymes 

 quite potently whereas /?-methylglucoside inhibits very little or not at 

 aU. The splitting of phenol-/?-glucosides by taka-/?-glucosidase is also in- 

 hibited by phenol-a-glucoside (Ezaki, 1940). The synthesis of polysaccha- 

 ride from a-D-glucose-1 -phosphate by muscle phosphorylase is not inhib- 

 ited by /?-D-glucose-l-phosphate; however, it is interesting that a-methyl- 



