Which class of inhibitors binds covalently to an enzyme, often affecting the active site?

The class of inhibitors that binds covalently to an enzyme is known as irreversible inhibitors. These inhibitors create a permanent modification to the enzyme structure, particularly at or near the active site, thereby preventing the enzyme from catalyzing its reaction effectively. Since the covalent bond is stable, the enzyme remains inactive until new enzyme molecules are synthesized.

Irreversible inhibitors are often utilized in drug design to target enzymes that must be tightly regulated or inhibited completely, such as in the treatment of certain diseases. An example includes aspirin, which irreversibly inhibits the cyclooxygenase enzyme involved in the inflammatory pathway.

In contrast, reversible inhibitors do not form covalent bonds and instead interact through non-covalent interactions such as hydrogen bonds, ionic bonds, or hydrophobic interactions. Competitive inhibitors bind to the active site but do not permanently alter the enzyme, allowing the inhibition to be reversed by increasing substrate concentration. Mixed inhibitors can inhibit the enzyme by binding to both the enzyme alone and the enzyme-substrate complex but similarly do not form covalent bonds. Therefore, the defining characteristic of irreversible inhibitors—forming covalent bonds that affect enzyme activity permanently—ensures that they are the correct answer in this context.