1. Prostaglandin, Leukotriene, and Thromboxane Synthesis Eric Niederhoffer SIU-SOM Linoleic acid Thromboxane A 2 synthase Lipoxygenase Arachidonic acid Prostaglandin G/H synthase Prostaglandins (PG)Leukotrienes (LT) Thromboxanes (TXA) Anti-inflammatory steroids Glucocorticoids NSAIDs aspirin Dazoxiben Benoxaprofen Zileuton

2. Prostaglandin Receptors http://www.caymanchem.com/app/template/scientificIllustrations%2CIllustration.vm/illustration/2018/a/z

3. Pathway Overview Phospholipase A 2 Membrane phospholipids Cyclooxygenase O2O2 Arachidonic acid PGG 2 PGH 2 PG hydroperoxidase 2GSH GSSG NSAIDS (aspirin) Anti-inflammatory steroids Glucocorticoids IL-1R IL-1 PGI 2 (PC)PGE 2 PGI 2 synthase PG endoperoxidase E isomerase

4. Differential Actions of Cyclooxygenases NSAIDs COX1 Constitutive COX2 Inducible Inflammatory Endothelial integrity Vascular patency Gastric mucosal integrity Bronchodilation Renal function Platelet function Inflammation Unwanted side- effects Therapeutic anti- inflammatory effects PGF 2  Proteases PGI 2 PGE 2 TXA 2 Housekeeping

5. COX-1 and COX-2 Comparison http://elfstrom.com/arthritis/nsaids/actions.html

6. COX-1 Specificity of Common NSAIDs Generally, the more selective for COX-1, the more serious side-effects appear http://elfstrom.com/arthritis/nsaids/actions.html

7. Review Questions How are prostaglandins, leukotrienes, and thromboxanes synthesized (substrates, enzymes, cofactors)? How do NSAIDs work? How do steroids work? What are the important characteristics of COX-1 and COX-2?