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STRUCTURE OF EICOSANOIDS
Generally, Eicosanoids are derived from 20-carbon (eicosa) polyunsaturated fatty acids,
most frequently Arachidonic acid.
Arachidonic Acid
Eicosanoids are divided into four main classes based on their structure;
Prostaglandins
Thromboxanes
Leukotrienes
Lipoxins
Structure Of Prostaglandins
Prostaglandins
Structure Of Thromboxanes
Thromboxanes have a unique structure compared to other eicosanoids, characterized by a
six-membered ether-containing ring. The thromboxane structure is based on a 20-carbon
skeleton derived from arachidonic acid. The defining feature is Oxane, a six-membered ring
with an oxygen atom.
Thromboxane
Stucture Of Leukotrienes
Leukotrienes are based on a 20-carbon skeleton derived from arachidonic acid. They have
a characteristic linear structure, with conjugated double bonds (triene) and specific
functional groups that determine their biological activity.
Types Of Leukotrienes
LTA4 - Contains an epoxide group within the conjugated triene system. It has a formula of
C20H30O3
LTA4
LTB4 – Derived from LTA4 by the addition of a hydroxyl group. The hydroxyl group is located
at carbon 12.
LTB4
LTC4
LTD4 - Formed from LTC4 by removal of the glutamic acid residue. Contains a cysteinyl-
leukotriene structure with an amino acid modification
LTD4
LTE4 - Formed from LTD4 by removal of the glycine residue. Contains a cysteinyl-
leukotriene structure with an amino acid modification.
LTE4
Structure Of Lipoxins
Lipoxins are derived enzymatically from arachidonic acid, an ω-6 fatty acid. Structurally,
they are defined as arachidonic acid metabolites that contain three hydroxyl residues and
four double bonds.
Lipoxin
SYNTHESIS OF EICOSANOIDS
Eicosanoids typically are not stored within cells but rather synthesized as required. They
derive from the fatty acids that make up the cell membrane and nuclear membrane. These
fatty acids must be released from their membrane sites and then metabolized initially to
products which most often are further metabolized through various pathways to make the
large array of products we recognize as bioactive eicosanoids. The key enzymes involved in
eicosanoid biosynthesis are cyclooxygenases (COX), lipoxygenases (LOX), and
cytochrome P450 (CYP) enzymes.
FUNCTIONS OF EICOSANOIDS
Eicosanoids are involved in various physiological processes such as inflammation,
immunity, pain modulation, blood clotting, and smooth muscle function.
Prostaglandins
PGE2
<Inflammation: Causes vasodilation and increased vascular permeability.
<Pain and Fever: Sensitizes pain receptors and raises body temperature.
<Gastrointestinal Protection: Reduces gastric acid secretion and increases mucus
production.
PGD2
<Allergic Responses: Involved in asthma and allergies.
<Sleep Regulation: Promotes sleep.
PGF2α
<Uterine Contraction: Induces labor.
<Bronchoconstriction: Affects bronchial muscle tone.
PGI2 (Prostacyclin)
<Vasodilation: Lowers blood pressure.
<Inhibits Platelet Aggregation: Prevents clot formation.
Leukotrienes
LTB4
<Chemotaxis: Attracts immune cells to inflammation sites.
<Leukocyte Activation: Enhances the immune response.
Cysteinyl Leukotrienes (LTC4, LTD4, LTE4)
<Bronchoconstriction: Contributes to asthma.
<Increased Vascular Permeability and Mucus Production: Leads to edema and mucus
secretion.
Lipoxins
LXA4 and LXB4
<Resolution of Inflammation: Promote the clearance of immune cells and inhibit further
recruitment.
REGULATIONS OF EICOSANOIDS
2. Inhibition by Drugs:
Pharmacological agents such as nonsteroidal anti-inflammatory drugs (NSAIDs) and
selective COX-2 inhibitors can inhibit eicosanoid synthesis by blocking the activity of COX
enzymes. NSAIDs, including aspirin, ibuprofen, and naproxen, inhibit both COX-1 and
COX-2 enzymes, while COX-2 inhibitors selectively target COX-2, reducing inflammation
and pain.
3. Autoregulation of Synthesis:
Some eicosanoids, such as prostaglandins, can regulate their own synthesis through
negative feedback mechanisms. For example, certain prostaglandins inhibit the
expression or activity of enzymes involved in their synthesis to prevent excessive
production.
4.Downregulation of Receptors:
Prolonged exposure to high levels of eicosanoids can lead to downregulation of their
receptors on target cells, reducing cellular responsiveness to these signaling molecules.
5. Desensitization Mechanisms:
Cells can develop desensitization mechanisms to dampen their response to continuous
stimulation by eicosanoids, helping to prevent overactivation of signaling pathways.
REFERENCES
Biochemistry by Jeremy M. Berg, John L. Tymoczko, and Lubert Stryer (2015).
Lehninger Principles of Biochemistry by David L. Nelson and Michael M. Cox (2021).
NCBI Bookshelf - Arachidonic Acid Metabolism. Available at: NCBI Bookshelf.