Which statement best describes aspirin's effect on COX enzymes?

• A. Irreversible inhibition of COX-1 and COX-2
• B. reversible inhibition of COX-1
• C. Inhibition of leukotriene synthesis
• D. Activation of COX-2

Answer: (A)

Aspirin works by acetylating a serine residue in the active site of cyclooxygenase enzymes, which irreversibly inactivates them. This means the enzymes cannot carry out their job of converting arachidonic acid to prostaglandins and thromboxanes, and the effect lasts for the life of the enzyme molecule. In platelets, which lack the ability to make new proteins, this irreversible inhibition of COX-1 lowers thromboxane A2 and gives an antiplatelet effect that lasts until new platelets are produced. In other cells, COX enzymes can be resynthesized, so the inhibition isn’t permanent there, but the initial acetylation still constitutes an irreversible block of the existing enzyme. The other statements aren’t correct because aspirin does not reversibly inhibit COX-1, does not inhibit leukotriene synthesis via COX, and does not activate COX-2.