Ibuprofen and related compounds block the hydrophobic channel by which arachidonate enters the cyclooxygenase active site.
Non-steroidal anti-inflammatory drugs ( NSAIDs ) , such as aspirin and derivatives of ibuprofen, inhibit cyclooxygenase activity of PGH 2 Synthase.
They inhibit formation of prostaglandins involved in fever, pain, & inflammation.
They inhibit blood clotting by blocking thromboxane formation in blood platelets.
Aspirin acetylates a serine hydroxyl group near the active site, preventing arachidonate binding.
The inhibition by aspirin is irreversible .
However, in most body cells re-synthesis of PGH 2 Synthase would restore cyclooxygenase activity.
Thromboxane A 2 stimulates blood platelet aggregation, essential to the role of platelets in blood clotting.
Many people take a daily aspirin for its anti-clotting effect, attributed to inhibition of thromboxane formation in blood platelets.
This effect of aspirin is long-lived because platelets lack a nucleus and do not make new enzyme.
The 1st step of the Linear Pathway for synthesis of leukotrienes is catalyzed by Lipoxygenase .
Mammals have a family of Lipoxygenase enzymes that catalyze oxygenation of various polyunsaturated fatty acid at different sites. Many of the products have signal roles.
E.g., 5-Lipoxygenase , found in leukocytes, catalyzes conversion of arachidonate to 5-HPETE (5-hydroperoxy-eicosatetraenoic acid).
5-HPETE is converted to leukotriene-A 4 , which in turn may be converted to various other leukotrienes .
Leukotrienes have roles in inflammation .
They are produced in areas of inflammation in blood vessel walls as part of the pathology of atherosclerosis .
Leukotrienes are also implicated in asthmatic constriction of the bronchioles.
Some leukotrienes act via specific G-protein coupled receptors (GPCRs) in the plasma membrane.
Anti-asthma medications include:
inhibitors of 5-Lipoxygenase , e.g., Zyflo (zileuton)
drugs that block leukotriene-receptor interactions . E.g., Singulair (montelukast) & Accolate (zafirlukast) block binding of leukotrienes to their receptors on the plasma membranes of airway smooth muscle cells.