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Regulation of Eicosanoid Biosynthesis in Endothelial Cells: Critical Role of De Novo Synthesis of Prostaglandin Endoperoxide Synthase

  • Kenneth Kun-Yu Wu
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 281)

Abstract

Prostaglandins are important autacoids participating in a myriad of physiologic and pathophysiologic processes. Biosynthesis of prostaglandins and eicosanoids is regulated at several enzymatic steps (1). As shown in Fig. 1, liberation of arachidonic acid from membrane phispholipids upon cell activation is catalyzed by phospholipases. This is a rate limiting step. Once arachidonic acid is liberated, it is metabolized via the cyclooxygenase and lipoxygenase pathways. The enzyme that is responsible for catalysis of arachidonic acid into endoperoxides is prostaglandin endoperoxide synthase (prostaglandin G/H synthase, prostaglandin H synthase or cyclooxygenase). This molecule possesses two enzymic activities: cyclooxygenase which catalyzes the oxygenation of arachidonic acid into prostaglandin G2 (PGG2) and peroxidase converting PGG2 into PGH2 (2). Prostaglandin H synthase is upregulated by peroxides including PGG2 but once PGG2 is converted to PGH2, oxygen radicals that are generated appear to cause irreversible inactivation of the cyclooxygenase activity (3-5). This leads to limited synthesis of PGH2. PGH2 is the common precursor for prostacyclin (PGI2), PGE2, PGF, PGD2 and thromboxane A2 (TXA2). With compromised PGH2 synthesis, production of these biologically active metabolites is consequently self-limited. This enzymatic step, hence, plays a central role in controlling eicosanoid biosynthesis.

Keywords

Arachidonic Acid Phorbol Ester Arachidonic Acid Metabolism Prostaglandin Biosynthesis Cyclooxygenase Activity 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer Science+Business Media New York 1990

Authors and Affiliations

  • Kenneth Kun-Yu Wu
    • 1
  1. 1.Department of Internal Medicine and Vascular Disease Research CenterUniversity of Texas Medical School at HoustonHoustonUSA

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