FIG 1.

Biosynthesis of various prostaglandins and leukotrienes. Membrane phospholipids are converted to AA by the PLA2 enzyme. Alternatively, AA can be synthesized from diacylglycerol (DAG), where DAG is converted by PLC to 2-AG intermediate, followed by MAGL degradation of 2-AG to AA. AA serves as a substrate of COX-1 and COX-2, which convert AA to PGH₂. Alternatively, AA is used by the 5-LOX enzyme to produce leukotrienes. PGH₂ is converted to PGE₂ by prostaglandin E synthase 1 (PGES-1) or PGD2 by hematopoietic prostaglandin D synthase (H-PGDS). PGD2 undergoes a dehydration reaction to form 15d-PGJ₂. LTA4 is derived from 5-LOX generated HPETE. LTA₄ can be processed further to LTB₄ via a hydrolysis reaction. Various other eicosanoids, such as resolvins and other lipoxins, are generated from the oxidation of polyunsaturated fatty acids other than AA, such as DHA and EPA.