Arachidonic acid–dependent eicosanoid synthesis pathways (AA-eicosanoid pathways)

The arachidonic acid–dependent eicosanoid synthesis pathways represent a complex network of enzymatic reactions that convert the polyunsaturated fatty acid arachidonic acid into potent lipid mediators known as eicosanoids, including prostaglandins, thromboxanes, leukotrienes, and epoxyeicosatrienoic acids. This cascade is primarily initiated by the release of arachidonic acid from cell membrane phospholipids by phospholipase A2, followed by metabolism through three main enzymatic routes: the cyclooxygenase (COX), lipoxygenase (LOX), and cytochrome P450 (CYP) pathways. These mediators play critical roles in regulating physiological processes such as vascular tone, platelet aggregation, and gastric mucosal protection, but are also central drivers of pathological inflammation, pain, and fever. (Source: StatPearls, 'Physiology, Eicosanoids'; PubMed, 'The arachidonic acid cascade as a target for atherosclerosis therapy'). Pharmacological intervention in these pathways is a cornerstone of modern medicine, particularly through the use of nonsteroidal anti-inflammatory drugs (NSAIDs) that inhibit COX enzymes to alleviate pain and inflammation. Other therapeutic strategies include leukotriene receptor antagonists for asthma and 5-LOX inhibitors for chronic inflammatory conditions. Because these pathways produce both homeostatic and inflammatory signals, systemic inhibition can lead to significant side effects, such as gastrointestinal bleeding or increased cardiovascular risk, necessitating the development of more selective inhibitors. (Source: NIH, 'Arachidonic Acid Metabolism'; Wikipedia, 'Arachidonic acid cascade').

Other names

Arachidonic acid cascadeEicosanoid metabolismCyclooxygenase/Lipoxygenase/Cytochrome P450 pathways

Drugs typically inhibit specific enzymes within the pathway, such as Cyclooxygenase-1 (COX-1), Cyclooxygenase-2 (COX-2), or 5-Lipoxygenase (5-LOX), to prevent the synthesis of pro-inflammatory eicosanoids like prostaglandins and leukotrienes.