Pgg211r-Hpete and 15r/S-Hpete are Formed From Different Conformers of Arachidonic Acid in the Prostaglandin Endoperoxide H Synthase-1 Cyclooxygenase Site

  • Elizabeth D. Thuresson
  • Karen M. Lakkides
  • William L. Smith
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 507)


Prostaglandin endoperoxide H synthases-1 and -2 (PGHS-1 and -2) catalyze the committed step in the formation of prostanoids (prostaglandins, thromboxane A2 (l-6). PGHSs catalyze two separate reactions: a cyclooxygenase reaction in which arachidonate is converted to prostaglandin G2 (PGG2) and a peroxidase reaction in which PGG2undergoes a two-electron reduction to PGH2. The cyclooxygenase reaction begins with a rate-limiting abstraction of the 13-proS hydrogen from arachidonate to yield an arachidonyl radical (7,8). This is followed by sequential oxygen additions at C-11 and C-15 to yield the prostaglandin endoperoxide PGG2. PGHSs exhibit some lipoxygenase activity producing small amounts of 11-hydroperoxy-5Z,8Z,12E,14Z-eicosatetraenoic acid (11-HPETE) and 15-hydroperoxy-5Z,8Z,11Z,13E-eicosatetraenoic acid (15-HPETE) from arachidonic acid (9, 10). Aspirin-acetylated PGHS-2, which has no cyclooxygenase activity, synthesizes 15R-HPETE (10,11). Studies comparing native and aspirinacetylated PGHS-2 have raised the possibility that arachidonate can bind in distinct orientations in the PGHS-2 active site to produce either PGG2, 1 l R-HPETE or 15RHPETE (10). Here we develop the concept that arachidonate can be bound in the cyclooxygenase active site of ovine (o)PGHS-1 in at least three different, catalytically competent arrangements that lead to PGG2, 11R-HPETE, and 15R/S-HPETE, respectively, and that these three arrangements of arachidonate occur subsequent to its entry into the cyclooxygenase active site.


Arachidonic Acid Lipoxygenase Activity Cyclooxygenase Activity Prostaglandin Endoperoxide Eicosatetraenoic Acid 
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Copyright information

© Springer Science+Business Media New York 2002

Authors and Affiliations

  • Elizabeth D. Thuresson
    • 1
  • Karen M. Lakkides
    • 1
  • William L. Smith
    • 1
  1. 1.Department of BiochemistryMichigan State University

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