Eicosanoids pp 21-36 | Cite as

The Physiological and Therapeutic Significance of Separate Pathways for Prostaglandin Synthesis

  • David L. DeWitt
Part of the NATO ASI Series book series (NSSA, volume 283)


There are two isozymes, prostaglandin endoperoxide synthase-1 and -2 (PGHS-1 and PGHS-2; also referred to as cyclooxygenase-1 and -2; COX-1 and COX-2) which catalyze the conversion of arachidonate to prostaglandin H2 (Smith, W. L. and DeWitt, 1995). These are central enzymes in two separate prostaglandin biosynthetic pathways. PGHS-1, an enzyme constitutively expressed in most tissues and in platelets, is a member of a biosynthetic pathway that responds instantaneously to stimulation by circulating hormones and produces prostaglandins that exit and act via cell surface receptors. The PGHS-1 pathway is also responsible for the production of prostaglandins in platelets and endothelial cells that acutely regulate vascular homeostasis and thrombus formation. PGHS-2, an enzyme which is expressed only in response to inflammatory, mitogenic, or other specialized stimuli, is the center of an inducible biosynthetic pathway that produces prostaglandins mediating specialized physiological responses such as inflammation, mitogenesis, or ovulation. Prostaglandins produced by PGHS-2 act extracellularly, but in addition, may signal within the nucleus. In this review, we will compare the structures, enzymology and regulation of expression of these two enzymes, and we will present evidence that indicates these pathways are physically as well as functionally separated, and likely coupled to different phospholipases or fatty acid substrate pools. The physiological as well as pharmacological significance of these separate system will also be examined.


Prostaglandin Synthesis Prostaglandin Endoperoxide Rheumatoid Synovial Fibroblast Specific Phospholipase Cyclooxygenase Reaction 
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Copyright information

© Springer Science+Business Media New York 1996

Authors and Affiliations

  • David L. DeWitt
    • 1
  1. 1.Department of BiochemistryMichigan State UniversityEast LansingUSA

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