Eicosanoids:

Prostaglandins and related compounds are collectively

known as eicosanoids. The term eicosanoid is derived
from “eicosa” meaning “twenty”, referring to the 20
carbon atoms in most of the molecules.
Most are produced from arachidonic acid, a 20-carbon
polyunsaturated fatty acid with four double bonds by
using interrelated pathway.
The eicosanoids are considered local hormones or
paracrine (Para=near) hormones. They have specific
effects on target cells close to their site of formation.
They are rapidly metabolized to inactive products, so
they are not stored and they are not transported to
distal sites within the body.
Examples of eicosanoids:
Prostaglandins (PGE2, PGF2 etc.)
Prostacyclins (PGI2)
Thromboxanes (TXA2)
Leukotrienes
Epoxyeicosatrienoic acid (EETs)
Prostacyclin and thromboxane are often considered as
the members of the prostaglandin group since they are
also cyclized derivatives (known as prostanoids).
The leukotrienes retain the straight chain configuration
of arachidonic acid.
Functions of eicosanoids:
Inflammation
Pain
Fever
Regulation of blood pressure
Blood clotting
Immune system modulation
Control of reproductive processes & tissue growth
Regulation of sleep/wake cycle

Note- Paracrines:
Chemicals secreted by a cell to act on cells in the
immediate vicinity via process of diffusion
Functions of eicosanoids:
PGE2
Bronchodilation
Vasodilation
Uterine muscle contraction
Hyperalgesia
Inhibits gastric acid secretion
Increases gastric mucus secretion
Mediation of fever

PGD2
Bronchoconstriction
Inhibition of platelet aggregation
Functions of eicosanoids:
PGF2α
Contraction of uterine muscles
Bronchoconstriction

PGI2
Inhibition of platelet aggregation
Vasodilation

TXA2
Platelet aggregation
Bronchoconstriction
Vasoconstriction
Structure of prostaglandin:
- Prostaglandins all have a cyclopentane ring.
- A letter code is based on ring modifications (e.g., hydroxyl
or keto groups). [Prostaglandins of the E and D series are
hydroxyketones, whereas the Fα prostaglandins are 1,3-
diols.]
- A subscript refers to the number of double bonds in the
two side-chains.
- The Greek letter (as in PGF2α) designates the position of
the hydroxyl group at C9.

Thromboxanes are similar but have instead a 6-membered

ring.
PGE2 (Prostaglandin E2) is an example of a prostaglandin,
produced from arachidonic acid.
 O

COOH

HO
OH
PGE2
Prostaglandin receptors:
Prostaglandins & related compounds are transported out of
the cells that synthesize them.
Most affect other cells by interacting with plasma membrane
G-protein coupled receptors.
Depending on the cell type, the activated G-protein may
stimulate or inhibit formation of cAMP, or may activate Ca++
release.
Eicosanoid synthesis:
Arachidonic acid, a 20-carbon fatty acid, is the primary
precursor of eicosanoids. Arachidonic acid is present as a
component of the phospholipids of cell membranes.
Free arachidonic acid is released from tissue phospholipids
by hydrolysis catalyzed by phospholipase A2 of cell
membrane or cytoplasm in response to various stimuli, eg,
physical injury, immune reactions.
Synthesized also from essential dietary fatty acids, esp.
linoleic acid.
There are two major pathways in the synthesis of the
eicosanoids from arachidonic acid:
- Cyclooxygenase pathway
- Lipoxygenase pathway
 Cell Membrane Phospholipids

Phospholipase A2

Arachidonic Acid

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Li
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Prostaglandins Leukotrienes
Thromboxanes
Prostacyclins
Cyclooxygenase pathway:
All eicosanoids with ring structures, that is, the
prostaglandins, thromboxanes, and prostacyclins, are
synthesized via the cyclooxygenase pathway.
Cyclooxygenase (COX) exists in at least two forms.
Cyclooxygenase-1 (COX-1) is found in many tissues;
the prostaglandins produced in these tissues by COX-1
appear to be important for a variety of normal
physiologic processes- protective prostaglandins in the
kidney and stomach, as well as the functional
thromboxane of platelets.
COX-1 is known as ‘house keeping enzyme’.
In contrast, Cyclooxygenase-2 (COX-2) is found
primarily in inflammatory cells (White blood cells); the
products of its actions play a major role in tissue injury,
eg, inflammation.
COX-2, not normally found in most tissues, expressed
under conditions of tissue damage and plays an active
role in the inflammatory response.
Lipoxygenase pathway:
Several lipoxygenases (most common 5-lipoxygenase)
can act on arachidonic acid to form leukotrienes or
lipoxins, depending on the tissue.
Leukotrienes assist in the pathophysiology of asthma.