122 



4. SUBSTRATE INHIBITION AND PRODUCT INHIBITION 



binding in the active and inhibiting groups {a = 139), indicating that 

 pyruvate is bound differently in the two complexes. Nevertheless such 

 reasoning in these cases is qualitative only and in the absence of pertinent 

 data is only speculation. On the other hand, substrate inhibition in some 

 systems, such as ribonuclease (Dickman and Ring, 1958), does not conform 

 to these kinetics and cannot be mechanistically interpreted. The depres- 

 sion of substrate inhibition by increasing ionic strength, without a simul- 



20mM 



(SUBSTRATE) 



Fig. 4-6. Examples of substrate inhibition plotted on a linear substrate concen- 

 tration scale. Curve 1: erythrocyte cholinesterase (Zeller and Bissegger, 1943). 

 Curve 2: lactate dehydrogenase (Hakala et al. 1956). Curve .3: steroid dehydro- 

 genase (Marcus and Talalay, 1955) (substrate concentration in {.iM). Curve 4: 

 human erythrocyte cholinesterase (Myers, 1952 c). 



taneous depression of ribonuclease activity, might indicate that the inhi- 

 bition is due to relatively nonspecific adsorption through electrostatic 

 interactions while the active complex involves a different type of binding. 

 The crystalline lactic dehydrogenase from heart catalyzes the reaction: 



Pyruvate -|- DPNH + H+ ^ lactate + DPN+ 



which can be readily followed spectrophotometrically. Potent substrate 

 inhibition is observed with pyruvate as shown in Fig. 4-6. The data conform 



