Eicosanoids

Eicosanoids are a group of biologically active lipids derived from arachidonic acid or other polyunsaturated fatty acids that are similar in structure. These compounds play a crucial role in various physiological and pathological processes within the body, including inflammation, immunity, and as messengers in the central nervous system.

Structure and Biosynthesis

Eicosanoids are derived from 20-carbon fatty acids, primarily arachidonic acid. The biosynthesis of eicosanoids begins with the release of arachidonic acid from cell membrane phospholipids by the action of the enzyme phospholipase A2. Once free, arachidonic acid can be metabolized through three major pathways:

• The cyclooxygenase (COX) pathway, which produces prostaglandins, thromboxanes, and prostacyclins.
• The lipoxygenase pathway, which produces leukotrienes and hydroxyeicosatetraenoic acids (HETEs).
• The cytochrome P450 epoxygenase pathway, which produces epoxyeicosatrienoic acids (EETs).

Functions

Eicosanoids have diverse roles in the body’s physiology and pathology, including:

• Inflammation: Prostaglandins and leukotrienes are key mediators of inflammatory responses, influencing vasodilation, vascular permeability, and leukocyte recruitment.
• Immune System: Eicosanoids modulate immune system responses by affecting the activity of various immune cells.
• Reproductive Processes: Prostaglandins play roles in ovulation, uterine contraction, and closure of the ductus arteriosus in newborns.
• Gastrointestinal Tract: They regulate secretion of gastric acid and are involved in the protection of the gastrointestinal lining.
• Nervous System: Eicosanoids act as neuromodulators and are involved in the pain pathway and fever response.

Clinical Significance

Due to their role in inflammation and immune responses, eicosanoids are targets for pharmaceutical intervention in various diseases:

• Nonsteroidal Anti-Inflammatory Drugs (NSAIDs), such as aspirin and ibuprofen, inhibit the COX enzymes, thereby reducing the production of pro-inflammatory prostaglandins.
• Leukotriene Receptor Antagonists and synthesis inhibitors are used to treat asthma and other allergic diseases by blocking the action or production of leukotrienes.

Research

Research continues to explore the role of eicosanoids in disease and health, aiming to develop new therapeutic strategies that target these pathways with greater specificity and fewer side effects.