EICOSANOIDS

• What are eicosanoids derived from?


  Long-chain fatty acids
• What does the term "eicosa" refer to in the context of eicosanoids?


  It means "twenty" in Greek, indicating the number of carbons in the fatty acids.
• Why are eicosanoids considered important biologically?


  They display a wide spectrum of important biologic activities.
• What are the two principal subgroups of eicosanoids?


  Leukotrienes and Prostaglandins
• What is arachidonic acid (AA) classified as?


  It is a 20-carbon fatty acid containing four double bonds.
• What type of fatty acid is arachidonic acid?


  Omega-6 fatty acid
• How is arachidonic acid released for eicosanoid synthesis?


  It is mobilized from the sn-2 position of membrane phospholipids by phospholipase A2 (PLA2).
• How many groups are in the PLA2 superfamily?


  16 groups
• What are the three classes of phospholipases that contribute to arachidonate release?


  Cytosolic PLA2, Secretory PLA2, Calcium-independent PLA2
• What activates the Ca2+ dependent translocation of cPLA2?


  Chemical and physical stimuli
• What happens to arachidonic acid under non-stimulated conditions?


  It is reincorporated into cell membranes, leading to negligible eicosanoid biosynthesis.
• What role does cPLA2 play in arachidonic acid release?


  It dominates in the acute release of arachidonic acid.
• What are the four routes for arachidonic acid metabolism?


  Enzymatic pathways (cyclooxygenase, lipoxygenase, P450 epoxygenase) and nonenzymatic pathways (isoeicosanoid pathway).
• What factors determine the type of eicosanoid synthesized?


  The substrate lipid species, cell type, and cell stimulus.
• What does COX metabolism of eicosapentaenoic acid yield?


  TXA3, which is relatively inactive.
• What do lipoxygenases produce?


  Leukotrienes
• What are the two forms of cyclooxygenase (COX)?


  COX1 and COX2
• Where is COX1 primarily found?


  In many tissues, important for various physiological processes.
• What is the primary role of COX2?


  It is important in the inflammatory process and produces prostacyclin and prostaglandins for renal function.
• What is thromboxane synthesized by?


  Platelets
• What is prostacyclin synthesized by?


  Endothelium
• What stimulates the production of eicosanoids?


  A wide variety of stimuli, including pain and immune reactions.
• What happens to arachidonic acid after it is released?


  It is metabolized by different enzymes to produce eicosanoids.
• What are the products of prostaglandin endoperoxide synthases (COX)?


  Prostanoids
• What is the role of COX-1 in the body?


  It generates prostanoids for "house-keeping" functions, such as gastric epithelial cytoprotection.
• What are eicosanoids synthesized from?


  Arachidonic acid
• What is the significance of eicosanoids in the body?


  They are important endogenous fatty acid autacoids.
• What are the main families of eicosanoids of clinical importance?


  • Straight-chain derivatives (leukotrienes)
  • Cyclic derivatives (prostacyclin, prostaglandins, thromboxane)
• What are the principal eicosanoid subgroups?


  Leukotrienes and cyclic molecules (prostaglandins, prostacyclin, thromboxane)
• How do leukotrienes differ from prostaglandins?


  Leukotrienes retain a straight-chain configuration, while prostaglandins are cyclized derivatives.
• What are the steps involved in the synthesis of eicosanoids?


  1. Activation of phospholipases
  2. Release of arachidonic acid from membrane phospholipids
  3. Metabolism by lipoxygenase (producing leukotrienes) or cyclooxygenase (producing prostacyclin, prostaglandins, thromboxane)
• What is the role of lipoxygenase in eicosanoid synthesis?


  It metabolizes arachidonic acid into straight-chain leukotrienes.
• What does cyclooxygenase (COX) produce?


  Prostacyclin, prostaglandins, and thromboxane
• What are the two forms of cyclooxygenase (COX) and their locations?


  COX-1 is found in many tissues, while COX-2 is primarily in inflammatory cells.
• What is the primary function of COX-2?


  It plays a major role in tissue injury and inflammation.
• Where is thromboxane synthesized?


  In platelets
• Where is prostacyclin synthesized?


  In the endothelial cells of blood vessels
• What is the half-life of naturally occurring eicosanoids?


  Very short, ranging from seconds to minutes
• What is an abortifacient?


  A drug used to cause an abortion
• What is the role of cyclooxygenase in eicosanoid synthesis?


  It converts arachidonic acid to PGG and PGH, precursors of prostaglandins.