Cyclooxygenase (prostaglandin G/H synthase) pathway
Chapter: 2
This enzyme is rate-limiting in the production of thromboxanes and prostaglandins (i.e., the prostanoids) from arachidonic acid (see Fig. 2-10, text). There are both constitutive and inducible isoforms of this enzyme, due to the existence of two different genes. The constitutive form (PGHS-1) is critical to the low-level production of arachidonic acid metabolites that are essential to the maintenance of homeostasis, e.g., maintenance of the integrity of the gastric mucosa. The gene that encodes PGHS-2, the inducible isoform, is selectively expressed in certain cell types, such as leukocytes. It allows them to produce large quantities of prostanoids at the site of an inflammatory stimulus. PGHS-2 is an excellent example of how selective expression of an inducible gene can be used to augment and amplify the initial response to an inflammatory stimulus. Aspirin and indomethacin interfere with the activity of cyclooxygenases, and corticosteroids, such as dexamethasone, interfere with expression of the gene that encodes PGHS-2.