Figure 2.

The effect of aspirin alone and of ibuprofen plus aspirin on platelet cyclooxygenase-1 (COX-1). A) The platelet prostaglandin (PG) G/H synthase-1 (COX-1) is depicted as a dimer, and the arachidonic acid substrate gains access to the catalytic site through a hydrophobic channel that leads to the core of the enzyme. B) Aspirin works by inhibiting access of arachidonic acid to the catalytic site by irreversibly acetylating a serine residue at position 529 in platelet COX-1. Interpolation of the bulky acetyl residue then permanently prevents metabolism of arachidonic acid into the cyclic endoperoxides PGG2 and PGH2. Because PGH2 is metabolized by thromboxane synthase into thromboxane A₂, aspirin prevents the formation of thromboxane A₂ by the platelets until new platelets are created. C) Nonsteroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen, are competitive inhibitors of the catalytic site, and cause the reversible inhibition of thromboxane A₂ formation during the dosing interval. Therefore, prior occupancy of the catalytic site by ibuprofen prevents aspirin from gaining access to its target serine (reproduced from reference [26], with permission).