Eicosanoids: Formation, Function, and Subclasses

Summary

This video explains the formation and function of eicosanoids, a group of local hormones derived from arachidonic acid in cell membranes. It covers the three main subclasses: prostaglandins, thromboxanes, and leukotrienes, detailing their roles in inflammation, pain, fever, immune responses, and blood clotting. Key enzymes like phospholipase A2, cyclooxygenase, and lipoxygenase are involved in their synthesis. The video also highlights their clinical relevance in treatments for conditions like asthma and labor induction, providing an overview of how these hormones influence bodily functions and contribute to various medical therapies.

Takeaways

• 😀 Eicosanoids are local hormones produced directly within tissues from arachidonic acid, a fatty acid present in cell membranes.
• 😀 The three major classes of eicosanoids are prostaglandins, thromboxanes, and leukotrienes.
• 😀 Prostaglandin H2 is a key intermediate in the synthesis of prostaglandins and thromboxanes.
• 😀 Leukotriene A4 is a precursor for the synthesis of various leukotrienes.
• 😀 Prostaglandin I2, also called prostacyclin, acts as an antagonist to thromboxane A2 and plays a role in preventing platelet aggregation.
• 😀 Eicosanoids are synthesized from 20-carbon unsaturated fatty acids, with arachidonic acid being the most common.
• 😀 Phospholipase A2 (PLA2) is the enzyme responsible for releasing arachidonic acid from cell membranes.
• 😀 Cyclooxygenase (COX) and lipoxygenase (LOX) are the key enzymes responsible for the formation of prostaglandins and leukotrienes, respectively.
• 😀 COX has two isoforms: COX-1, which is constantly active, and COX-2, which is induced during inflammatory responses.
• 😀 Prostaglandins, thromboxanes, and leukotrienes have different physiological effects depending on their site of production, including pain, inflammation, vasodilation, and immune response regulation.

Q & A

What are eicosanoids and how are they different from classical hormones?

Eicosanoids are local hormones that are produced directly within tissues rather than in endocrine glands. Unlike classical hormones, which are transported to target sites, eicosanoids exert their effects locally, within the tissue where they are synthesized.

What are the three major subclasses of eicosanoids?

The three major subclasses of eicosanoids are prostaglandins, thromboxanes, and leukotrienes.

How are eicosanoids formed from arachidonic acid?

Eicosanoids are formed from arachidonic acid through the action of specific enzymes. Arachidonic acid is released from cell membranes by phospholipase A2 (PLA2), and then it is converted to prostaglandin H2 by cyclooxygenase (COX) or to leukotriene A4 by lipoxygenase (LOX).

What is the function of phospholipase A2 (PLA2) in eicosanoid synthesis?

Phospholipase A2 (PLA2) catalyzes the release of arachidonic acid from phospholipids in the cell membrane, which is the first step in eicosanoid synthesis.

What are the differences between COX-1 and COX-2 enzymes?

COX-1 is constitutively active in most tissues, performing housekeeping functions like protecting the stomach lining. COX-2, on the other hand, is induced during inflammatory responses and is involved in producing prostaglandins related to inflammation and pain.

What is the role of cyclooxygenase (COX) in eicosanoid formation?

Cyclooxygenase (COX) converts arachidonic acid into prostaglandin H2, which is a precursor for the synthesis of other prostaglandins and thromboxanes.

How does lipoxygenase contribute to eicosanoid synthesis?

Lipoxygenase (LOX) converts arachidonic acid to leukotriene A4, which is further metabolized into other leukotrienes. LOX incorporates oxygen into the fatty acid without forming a cyclic structure.

What is the significance of the subscript numbers in eicosanoid names?

The subscript numbers in eicosanoid names indicate the number of carbon double bonds in the molecule. Prostaglandins and thromboxanes typically have two double bonds (subscript 2), while leukotrienes have four double bonds (subscript 4).

What are the main physiological functions of prostaglandin E2 (PGE2)?

Prostaglandin E2 (PGE2) is involved in mediating pain, inflammation, and fever. It also has protective effects in the stomach, promotes kidney vasodilation, stimulates uterine contractions, and enhances sperm motility in the prostate.

How does thromboxane A2 affect blood vessels and platelets?

Thromboxane A2 causes vasoconstriction and promotes platelet aggregation, both of which are crucial for blood clotting and coagulation.

What is the clinical relevance of leukotrienes in asthma treatment?

Leukotrienes, especially leukotrienes C4, D4, and E4, cause bronchoconstriction in the lungs, which is a key factor in asthma attacks. Leukotriene antagonists, like montelukast, are used to block these effects and prevent asthma symptoms.

What are some clinical uses of eicosanoids in medicine?

Eicosanoids are used in gynecology for labor induction and in neonatology to keep the ductus arteriosus open in newborns. Their roles in inflammation and immune responses also make them targets for various drugs.