454 THE BIOCHEMISTRY OF B VITAMINS 



tions of slope and intercept which distinguish competitive inhibition from 

 noncompetitive inhibitions. 



A more specialized type of inhibition, "quadratic" inhibition, has been 

 described, in which the plots for different concentrations of inhibitor have 

 different intercepts and begin with near zero slopes which change to a 

 common slope identical with that in the absence of the inhibitor. 18 This 

 is easily differentiated from competitive inhibition. 



In a consideration of the rates of biological processes rather than of 

 isolated enzymes, the application of the methods of differentiation of 

 competitive inhibition from other types by rate studies is somewhat com- 

 plicated by the interrelationship of the rate of the biological process and 

 the rate of the specific inhibited enzymatic reaction. In the presence of 

 the inhibitor at effective concentrations, the rate of the specific enzymatic 

 reaction is the limiting process in eliciting an observable response from 

 the biological system. Under such conditions, the reciprocal of the rate 

 of the biological process plotted against the reciprocal of the substrate 

 concentration would give a linear function over a defined region in the 

 plot. The extrapolated intercept would not represent the maximum rate 

 of the biological process, but rather the theoretical maximum rate of the 

 biological process when the inhibited enzyme is saturated with substrate 

 and is still the limiting reaction. This is a purely hypothetical condition, 

 since many enzyme systems other than the specific one concerned would 

 most likely be somewhat less efficient under these conditions. As indicated 

 in Figure 2, the rate can increase only to the maximum rate of the 

 complete biological process and not to the maximum theoretical rate of 

 the specific enzyme. 



Another complication is the fact that many biological systems have the 

 ability to synthesize the substrate. Hence, while the concentration of the 

 substrate supplied to the system can be diminished to zero, the concentra- 

 tion synthesized by the biological system limits the lowest concentration 

 of substrate attainable. Thus, the value of 1/[S] can be increased only 

 to a definite value, and further decreases in exogenous supply of the 

 substrate do not alter the rate of the biological process. This is indicated 

 in Figure 2. With increasing 1/[S] values the transition from the normal 

 linear relationship of 1/[S] versus 1/r to the constant minimum rate of 

 the biological process for a defined concentration of inhibitor may be 

 either an abrupt change or a gradual one depending upon the system. 

 For example, there may be a very abrupt change in systems in which the 

 concentration of substrate outside the biological system is not appreciably 

 altered by the biological system, and the concentration of substrate 

 within and without the system attain equilibrium. Concentrations of 

 exogenous substrate below that synthesized by the system would not 



