arachidonic acid
Summary
Arachidonic acid is a 20-carbon polyunsaturated fatty acid that serves as the precursor to important inflammatory mediators including prostaglandins, leukotrienes, and thromboxanes. It is released from membrane phospholipids by phospholipase A2 and metabolized via cyclooxygenase (COX) and lipoxygenase pathways.
Detail
Arachidonic acid is an essential fatty acid stored in cell membrane phospholipids and released by phospholipase A2 when cells are stimulated by inflammatory signals, trauma, or other stimuli. Once released, it undergoes metabolism through two major enzymatic pathways: (1) The cyclooxygenase pathway (COX-1 and COX-2) produces prostaglandins (PGE2, PGI2, PGF2α) and thromboxanes (TXA2), which mediate inflammation, pain, fever, and platelet aggregation; (2) The lipoxygenase pathway produces leukotrienes (LTC4, LTD4, LTE4, LTB4), which cause bronchoconstriction, increased vascular permeability, and neutrophil chemotaxis. This is clinically significant because NSAIDs work by inhibiting COX enzymes, reducing prostaglandin synthesis, while corticosteroids inhibit phospholipase A2, blocking arachidonic acid release entirely. Understanding this cascade is crucial for comprehending anti-inflammatory drug mechanisms and the pathophysiology of conditions like asthma, arthritis, and cardiovascular disease.
Sources
- Lippincott Illustrated Reviews: Biochemistry
- Katzung Basic & Clinical Pharmacology
- Robbins and Cotran Pathologic Basis of Disease
- First Aid for the USMLE Step 1
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