Arachidonate metabolism (AA metabolism)

Arachidonate metabolism is a complex biochemical network responsible for converting arachidonic acid, a 20-carbon polyunsaturated fatty acid, into bioactive lipid mediators known as eicosanoids (StatPearls, 2023). This metabolic cascade is initiated by the release of arachidonic acid from cell membrane phospholipids by phospholipase A2 (PLA2) enzymes. Once released, the acid is metabolized via three primary enzymatic routes: the cyclooxygenase (COX) pathway, the lipoxygenase (LOX) pathway, and the cytochrome P450 (CYP) pathway (Journal of Lipid Research, 2009). These pathways produce a diverse array of signaling molecules, including prostaglandins, thromboxanes, leukotrienes, and epoxyeicosatrienoic acids. These metabolites act as potent local signaling molecules that regulate a wide array of physiological and pathological processes, including the inflammatory response, vascular tone, platelet aggregation, and pain perception (Nature Reviews Drug Discovery, 2014). Because of its central role in inflammation, the arachidonate metabolism pathway is a major focus of pharmacology, with nonsteroidal anti-inflammatory drugs (NSAIDs) and leukotriene modifiers being among the most widely used medications globally. However, therapeutic intervention is complicated by the fact that many eicosanoids also maintain homeostatic functions, such as gastric mucosal protection and renal blood flow regulation, leading to potential side effects when the pathway is broadly inhibited. Dysregulation of the arachidonate cascade is a hallmark of many chronic inflammatory conditions, including rheumatoid arthritis, asthma, and atherosclerosis.

Other names

Arachidonic acid cascadeEicosanoid metabolismProstaglandin synthesis pathwayAA metabolism

Inhibition of enzymes (e.g., COX-1, COX-2, 5-LOX) or antagonism of downstream eicosanoid receptors (e.g., CysLT1, TP receptor) within the arachidonic acid cascade.