title: The enzymology of prostaglandin endoperoxide H synthases-1 and -2.
abstract: We summarize the enzymological properties of prostaglandin endoperoxide H synthases (PGHs)-1 and -2, the enzymes that catalyze the committed step in prostaglandin biosynthesis. These isoenzymes are closely related structurally and mechanistically. Each catalyzes a peroxidase and a cyclooxygenase reaction at spatially separate but neighboring, electronically interrelated active sites. The peroxidase is necessary to activate the cyclooxygenase; oxidation of the heme group of the peroxidase by peroxide leads to oxidation of a cyclooxygenase active site tyrosine. The tyrosine radical abstracts hydrogen from arachidonic acid to form an arachidonate radical which reacts sequentially with two oxygen molecules forming the intermediate product PGG2. PGG2 is then reduced by the peroxidase activity to PGH2. Based on the crystal structure of PGHS-1 arachidonate complex, it is now possible to envision how arachidonate is bound and oxygenation occurs. Recently, it has become possible to distinguish kinetically between the cyclooxygenase and peroxidase suicide inactivation reactions.
authors.affiliation: Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing 48824, USA. smithww@msu.edu
authors.forename: William L
authors.initials: WL
authors.lastname: Smith
authors.forename: Inseok
authors.initials: I
authors.lastname: Song
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000378:metabolism; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000378:metabolism; D007527:Isoenzymes / Q000737:chemistry / Q000378:metabolism*; D015394:Molecular Structure; D011451:Prostaglandin-Endoperoxide Synthases / Q000737:chemistry / Q000378:metabolism*; D011453:Prostaglandins / Q000096:biosynthesis*; D013379:Substrate Specificity
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D011453:Prostaglandins; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases