Vmax, Km, and intrinsic clearance

The less frequently encountered uncompetitive inhibition occurs when a chemical binds to the enzyme-substrate complex. The catalytic function is affected without interfering with substrate binding. The inhibitor causes a structural distortion of the active site and inactivates it (Voet and Voet 2004). This has the effect of reducing the available enzyme for the reaction, and hence reduces Vmax, and also drives the reaction (E + S ES) to the right, hence decreasing Km. 

It is noteworthy that these types of reversible metabolic inhibitions can also be applied to active transport processes. In fact, Sugita et al. (1982) have described noncompetitive inhibition as the mechanism of binary interaction between sodium tolbutamide and 3 other drugs (sulfaphenozol, sodium sulfadimethoxazole, and sodium sulfadimethoxine) (Table 2.3). 

When an inhibitor binds irreversibly to the enzyme at the active site, this usually inactivates the enzyme s catalytic activity. This type of inhibition decreases the concentration of the functional enzyme and therefore results in a decrease of Vlliax (i.e., an irreversible loss of enzyme activity). Briefly, the modeling of irreversible 

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Table 2.2 Description of the effect of reversible metabolic inhibition on the parameters Vmax, Km, and intrinsic clearance...

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