Arachidonic acid–dependent eicosanoid pathway (AA pathway)

The arachidonic acid–dependent eicosanoid pathway is a central metabolic network that converts the polyunsaturated fatty acid arachidonic acid into a diverse array of bioactive lipid mediators called eicosanoids (StatPearls, 2023). This process is initiated by the release of arachidonic acid from cell membrane phospholipids by phospholipase A2 (PLA2) in response to various stimuli. The free arachidonic acid is then metabolized via three primary enzymatic routes: the cyclooxygenase (COX) pathway leading to prostaglandins and thromboxanes, the lipoxygenase (LOX) pathway producing leukotrienes and lipoxins, and the cytochrome P450 (CYP) pathway generating epoxyeicosatrienoic acids (Nature Reviews Drug Discovery, 2005). These eicosanoids act as potent local signaling molecules that regulate critical physiological processes such as inflammation, vascular tone, platelet homeostasis, and gastric mucosal protection (Journal of Lipid Research, 2009). Dysregulation of these pathways is a hallmark of chronic inflammatory conditions, asthma, and certain cancers, making the enzymes and receptors within this cascade some of the most significant targets in pharmacology, including nonsteroidal anti-inflammatory drugs (NSAIDs) and leukotriene modifiers (NIH, 2022).

Other names

Arachidonic acid cascadeEicosanoid metabolismProstanoid and leukotriene biosynthesis pathway

Inhibition of cyclooxygenase (COX-1/COX-2) enzymes, inhibition of 5-lipoxygenase (5-LOX), and antagonism of cysteinyl leukotriene receptors (CysLT1) (StatPearls, 2023; Nature Reviews Drug Discovery, 2005).