Prostaglandin EndoperoxideH₂Synthases‐1 and ‐2

Abstract

The prostaglandin endoperoxide H 2 synthase (PGHS) isozymes 1 and 2 are membrane bound, heme‐dependent enzymes that catalyze the committed step in the conversion of polyunsaturated fatty acids to prostanoids and thromboxanes. The PGHS isozymes, which are also known as cyclooxygenases, produce prostaglandin H 2 in two sequential enzymatic steps – a bis‐oxygenase (cyclooxygenase) reaction generates prostaglandin G 2 from arachidonic acid and a hydroperoxidase reaction creates the final product, prostaglandin H 2 . The PGHS isozymes are also the primary targets of nonsteroidal anti‐inflammatory drugs (NSAIDs), such as aspirin and ibuprofen, and recent pharmacological research efforts have led to the development of isoform selective drugs like Celebrex® and Vioxx®. In this chapter, we discuss the biochemistry, enzymology, and the structural biology of the PGHS isozymes and their relevance to prostanoid physiology and NSAID pharmacology.