ARACHIDONIC METABOLISM PATHWAY 

Introduction

Arachidonic Acid pathway describes the synthesis of different Prostanoids (PGs, TXs, Prostacyclin) and Leukotrienes, Cysteinyl Leukotrienes, and Lipoxanes.

Steps of AA pathway

Step – 01 (Activation of Phospholipase A2 and release of Arachidonic Acid)

  • Release of AA from phospholipid membrane is carried out by Phospholipase A2
  • Stimuli initiates the Ca+2 dependent translocation of cytosolic PLA2 to the membrane where it hydrolyses the AA and releases It into the cytosol.

Step – 02 (Cyclooxygenase Pathway) 

  1. Arachidonic acid is converted to Prostaglandin G2 and Prostaglandin H2 catalyzed by Cyclooxygenase (COX-1 & COX-2) enzyme. 
  2. Prostaglandin H2 is then Converted to various Prostanoids by several enzymes-
  • Thromboxane A2 (Converted by Thromboxane A synthase) 
  • Prostaglandin E2 (Microsomal Prostaglandin E synthase and cytosolic prostaglandin E Synthase) 
  • Prostaglandin F 2 alpha (Prostaglandin F synthase) 
  • Prostaglandin D2 (L-PGDs) 
  • Prostacyclin (PGI2) (Prostaglandin I synthase) 


Step – 03 (Lipoxygenase Pathway) 

Arachidonic Acid also undergoes some other enzymatic conversion producing Some Leukotrienes, Cysteinyl leukotrienes and Lipoxins.  
This pathway mainly catalyzed by lipoxygenase (5-LOX, 12-LOX and 15-LOX) enzyme.
  • At first Arachidonic Acid is converted to 5-HPETE catalyzed by 5-LOX
  • 5-HPETE is converted to leukotriene A4 (LTA4) catalyzed by 5- LOX
  • LTA4 then converted to different Lipoxins, leukotriene, and Cysteinyl Leukotrienes 
  1. LTA4 is converted to Lipoxin A4 and Lipoxin B4 by 12-LOX enzyme
  2. LTA4 is converted to leukotriene B4 by LTA4 hydrolase enzyme
  3. LTA4 is converted to different cysteinyl leukotrienes (LTC4, LTD4, LTE4) 




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