128 



4. SUBSTRATE INHIBITION AND PRODUCT INHIBITION 



any event, the shift in (Sq) to higher values with increasing NaCl concen- 

 tration would be due to the decreased affinity of the enzyme for the sub- 

 strate. It might be possible to unravel the exact mechanism by a quanti- 

 tative study of the effects of changes in pH on the inhibition, since the reac- 

 tions at the two sites would respond differently. Addition of CaClg at 5 

 mM increases K^ five fold without changing aK^, this would be expected 

 if Ca++ competed effectively with acetylcholine for the anionic site but did 

 not alter binding at the esteratic site, upon which the value of aK^ mainly 

 depends. The marked activation of the rate by CaClg would also imply 

 an effect on the esteratic site, probably by combination with an adjacent 

 group. It is odd that Augustinsson (1948) reported no effects of CaCla 

 (1 — 10 mM) and very little effect of KCl (100 mM) on the substrate in- 

 hibition of any type of cholinesterase. The pSo was shifted only 0.1 unit 

 on the average by KCl. 



Very few investigations have been made on the relation of substrate 

 structure to substrate inhibition, so that the results of Marcus and Talalay 

 (1955) on the /?-hydroxysteroid dehydrogenase are of great interest. The 

 inhibition curves for nine steroids are shown in Fig. 4-12 and the reaction 



CS) V 10 M 



Fig. 4-12. Substrate inhibition of ^-hydroxysteroid dehydrogenase by nine steroids 



whose structures and kinetic constants are given in the accompanying tabulation. 



(From Marcus and Talalay, 1955.) 



