These three groups are collectively called eicosanoids, derived from arachidonic acid via the cyclooxygenase (COX) or lipoxygenase pathways.
Leukotrienes are eicosanoids derived from arachidonic acid via the lipoxygenase (LOX) pathway.
They are primarily involved in immune and inflammatory responses.
Major Leukotrienes:
LTB4 (Leukotriene B4):
Functions: Acts as a potent chemotactic agent, attracting neutrophils to sites of inflammation.
LTC4, LTD4, LTE4 (Cysteinyl Leukotrienes):
Functions: Induce bronchoconstriction, increase vascular permeability, and contribute to inflammatory responses.
Synthesis:
Immune Cells Activation: Upon stimulation, cells like mast cells, eosinophils, and macrophages release arachidonic acid.
LOX Pathway: 5-LOX converts arachidonic acid into leukotriene A4 (LTA4), which is further transformed into LTB4 or conjugated with glutathione to form LTC4, LTD4, and LTE4.
Arachidonic acid → (5-lipoxygenase) → Leukotriene A4 → LTB4, LTC4, LTD4, LTE4.
Physiological and Pathological Roles:
Asthma and Allergies: Cysteinyl leukotrienes mediate bronchoconstriction and increased mucus production.
Inflammation: LTB4 recruits and activates leukocytes, amplifying the inflammatory response.
Autoimmune Diseases: Involved in the pathogenesis of conditions like rheumatoid arthritis.
Pharmacological Effects:
Bronchoconstriction: Cause tightening of airway muscles, contributing to asthma and allergic reactions.
Increased Vascular Permeability: Promote leakage of fluids into tissues, leading to edema.
Chemotaxis: Attract immune cells like neutrophils to sites of inflammation.
Mucus Secretion: Stimulate mucus production in the respiratory tract.
Pain Sensitization: Enhance pain perception during inflammatory responses.
Drug targets:
5-lipoxygenase inhibitor: Zileuton (used in asthma).
Leukotriene receptor antagonists: Montelukast, Zafirlukast (for asthma prophylaxis).