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 , with permission).