Inhibitors Permanently Alter the Enzyme Structure

Irreversible Inhibitors Permanently Alter the Enzyme Structure 

Competitive, noncompetitive, and uncompetitive inhibition are all reversible. If the inhibited enzyme is dialyzed to remove the inhibitor, the enzymatic activity recovers. There are, however, inhibitors that react essentially irreversibly, usually by forming a covalent bond to an amino acid side chain or a bound coenzyme. Examples of such inhibitors are given in table 7.4. Like reversible inhibitors, irreversible inhibitors can change either Umax or Km or both. 

Irreversible inhibitors often provide clues to the nature of the active site. Enzymes that are inhibited by iodo-acetamide, for example, frequently have a cysteine in the active site, and the cysteinyl sulfhydryl group often plays an essential role in the catalytic mechanism (fig. 7.18). An example is glyceraldehyde 3-phosphate dehydrogenase, in which the catalytic mechanism begins with a reaction of the cysteine with the aldehyde substrate (see fig. 12.21). As we discuss in chapter 8, trypsin and many related proteolytic enzymes are inhibited irreversibly by diisopropyl-fluorophosphate (fig. 7.18), which reacts with a critical serine residue in the active site. 

Enzymes are biological catalysts. Kinetic analysis is one of the most broadly used tools for characterizing enzymatic reactions. 

The rate of a reaction depends on the frequency of collisions between the reacting species and on the fraction of the collisions that produce products. The former depends on the concentrations of the reactants the latter depends on temperature and activation free energy AG. AG can be interpreted as the free energy needed to convert the reactants to a transition state. A catalyst increases the reaction rate by lowering AG.  

---

Competitive Inhibitors Bind at the Active Site Noncompetitive and Uncompetitive Inhibitors Do Not Compete Directly with Substrate Binding Irreversible Inhibitors Permanently Alter the Enzyme Structure... 

---