Overview
Arachidonic acid (AA) is a 20-carbon omega-6 polyunsaturated fatty acid (20:4n-6) that serves as the primary substrate for prostaglandin and leukotriene synthesis via COX-2 and 5-LOX pathways. It is the dominant pro-inflammatory lipid mediator — and its balance with anti-inflammatory omega-3 fatty acids (EPA/DHA) determines the inflammatory tone across multiple disease signatures.
Microbiome Connection
- COX-2/NF-kB axis: Metal-driven NF-kB activation upregulates COX-2, increasing arachidonic acid conversion to pro-inflammatory prostaglandin E2 (PGE2) — the same pathway activated by microbial LPS via TLR4 [1].
- NSAIDs and microbiome: NSAIDs (COX inhibitors blocking AA metabolism) cause gut microbiome disruption and intestinal injury, paradoxically increasing dysbiosis while reducing inflammation [1].
- Endometriosis metabolomics: Altered arachidonic acid levels in fecal metabolomics of endometriosis models [2].
- Diabetic ED: Fatty acid profiles including AA altered in diabetic erectile dysfunction [3].
Resolution Pathway
Arachidonic acid is also the precursor for lipoxins — pro-resolving mediators that actively terminate inflammation. The balance between pro-inflammatory (prostaglandins) and pro-resolving (lipoxins) AA metabolites depends on the enzymatic context, which metals can disrupt.
Cross-References
- inflammation — AA/COX-2 as pro-inflammatory pathway
- omega 3 fatty acids — anti-inflammatory counterbalance to AA
- lipid metabolism — broader lipid context
- lipid peroxidation — AA as substrate for oxidative damage
- nf kappa b — NF-kB drives COX-2/AA pathway