The principal eicosanoids of biological significance to humans are a group of molecules derived from the 20:4 (20 carbons: 4 sites of unsaturation) fatty acid, arachidonic acid.

1. Eicosanoids

2. History Of Eicosanoids
Ulf Von Euler, won Nobel prize in
medicine and physiology .
First to discover the
prostaglandins. He found the
presence of PG in human
semen .
Presumed that they were
synthesized by the prostate
glands and hence named as PG
but realized that it was present
in all the tissues except for
erythrocytes.
Ulf Von Euler

3. Eicosanoids
The principal eicosanoids of biological
significance to humans are a group of molecules
derived from the 20:4 (20 carbons: 4 sites of
unsaturation) fatty acid, arachidonic acid.
These eicosanoids primarily consist of the
prostaglandins (PG), thromboxanes (TX),
leukotrienes (LT), and lipoxins (LX). The PG and
TX are collectively identified as prostanoids.

4. 20
Eicosanoids
Arachidonic
Acid
Means 20, in Greek it means 20 carbon fatty
acid
1
COOH
Prostaglandins Leukotrienes
CYCLOOXYGENASE LIPOXYGENASE

5. Classification Of Eicosanoids
Eicosanoids
Prostanoids
• Leukotrienes
• Lipoxins
Prostaglandins
(PGs)
Prostacyclins
(PGI)
Thromboxanes
(Tx)

6. Prostaglandins
• Prostaglandins are group of hormone like
substances, they plays a role in a wide
variety of physiological processes.
• Prostaglandins act in a manner similar to
that of hormones by stimulating target cells
into action .
• However they differ from hormones in that
they act locally near the site of synthesis and
are metabolized very rapidly

7. Structure Of Prostaglandins
• Prostaglandins are derived from 20 carbon
fatty acid namely prostanoic acid.
COOH
CH3
20
11
13
9
OH
14
Prostanoic acid

8. Chemistry Of Prostaglandins
Prostaglandins are divided into four main groups
• PG-E : PGE1,PGE 2 and PGE3
• PG-F : PGF1, PGF2 and PGF3
• PG-A :PGA1,PGA2,19-OH PGA2
• PG-B : PGB1,PGB2,19-OH PGB1 and
19-OH PGB2.

9. Synthesis Of Prostaglandins
Membrane bound phospholipids
PhospholipaseA2
Arachidonic acid
Prostaglandins and
Thromboxanes
Cyclooxygenase
Leukotrienes and
Lipoxins
Lipoxygenase

10. Regulation Of Synthesis Of
Prostaglandins
Membrane bound phospholipids
Arachidonic acid
Phospholipase A2
Stimulants
• Bradykinin
• Epinephrine
• Angiotensin
• Hypoxia
• Trauma
+
-
Inhibitors
Corticosteroids
Prostaglandins and
Thromboxanes
Cyclooxygenase
-
Aspirin
Indomethacin
Ibuprofen
Leukotrienes and
Lipoxins
Lipoxygenase

11. Cyclooxygenase inhibition by
Asprin
CO2H
OCOCH3
Acetylsalicylic acid
(aspirin)
CO2H
O - CCH3
O
COX
HOH2C
Ser-530
COX
CH2OCOCH3
Irreversible inhibition of COX by acetylation
of the active site
People take a daily dose of aspirin for its anti-clotting effect.
This is due to inhibition of thromboxane formation in
blood platelets.

12. COX -2 Inhibitor - NSAID
O
O
SO2CH3
F3C
N
N
CH3
SO2NH2
Rofecoxib (Vioxx) Celecoxib (Celebrex)
NSAID-non steroidal antiinflammatory drugs
COX has 2 domains: catalytic domain and membrane binding domain.
Membrane has a long & narrow channel by which AA enters active site.
COX inhibitors inhibit this channel.

13. Mechanism Of Action Of
Prostaglandins
• Prostaglandins bind to specific receptors on the
plasma membrane of target cells and bring about
changes in the concentration of second
messengers which may be cyclic AMP, Ca2+ or
cyclic GMP which then mediate biological effects.

15. • PGEs : They mostly act through second
messenger Cyclic AMP.
• PG – Fs and Tx – A2: These use Ca++
as second messenger in some tissues.
• PG – F2 : Action is mediated through
Cyclic GMP as second messenger.
CONTD…

16. Functions Of Prostaglandins
Prostaglandins have numerous and diverse
functions.
Antihypertensive action :
• The prostaglandins (PGE,PGA and PGI2) are
vasodilators.
• Increased blood flow and decreased peripheral
resistance so there is a fall in blood pressure.
• PGs are used in treatment of hypertension.

17. Role of PG in inflammation:
• PGE1 and PGE2 induce the symptoms of
inflammation (redness,swelling,edema)
due to arteriolar vasodilation.
• PG are considered as natural mediators
of inflammatory reactions of rheumatoid
arthritis ,psoriasis(skin),conjuctivitis(eyes).
• Corticosteroids are frequently used to
inhibit the inflammatory response.

18. PG and Reproduction
• PGE 2 and PGF2 are widely used for
medical termination of pregnancy and
induction of labour, it increases the uterine
contraction.

19. Action on GI secretions
Gastric secretions :
• PG’s PGE1,E2 and A1 inhibit gastric secretion.
• Decrease in the acid and pepsin content.Action
is exerted directly on secretory cells through C –
AMP.
• PGs are used for preventing gastric ulcers.

20. Intestinal Secretion :
• Mucus secretion is increased.
• There is substantial movement of water
and electrolytes into the intestinal lumen.
• It increases the motility of the intestine thus
causes diarrhoea.
Cont’d…

21. Effect of PG on pain and fever
• Pyrogens (fever producing agents)promote PG
synthesis leading to the formation of PGE2 in the
hypothalamus, the site for regulation of body
temperature.
• PGE2 along with histamine and bradykinin causes
pain. Migraine is due to PGE2.Asprin and other non
steroidal drugs inhibit PG synthesis and thus
control fever and relieve pain.

22. Effect of PG on respiratory
function
• PGE is a bronchodilator whereas PGF
acts as broncho constrictor of smooth
muscles. PGE and PGF oppose the action
of each other in the lungs.PGE1 and E2 are
used in the treatment of asthma.

23. Effect on renal function
Intravenous infusion of PGE and PGA
produces:
• Substantial increase in renal plasma flow .
• Increase in GFR.
• Increased urinary flow.

24. Effect on metabolism
• PGE inhibits lipolysis.
• PGE has also some insulin like effects on
carbohydrate metabolism.

25. Thromboxanes
O
COOH
OH
11
• Thromboxanes are also derived from
prostanoic acid but instead of 5- carbon
cyclopentane ring of PG ,thromboxanes
have a 6- membered oxane ring.
9
O 12
OH
5
6

26. Function Of Thromboxanes
• Thromboxanes are synthesized in
platelets and upon release cause
vasoconstriction and platelet aggregation.
• It stimulates steroid production by adrenal
cortex.
• Exerts PTH like effects on bone ,it causes
increased mobilization of calcium from
bones.

27. Prostacyclins VsThromboxanes
Prostacyclins
(PG I2)
Coronary
arteries
Dilates
Thromboxanes
Blood pressure
lowers Raises
Platelet
Aggregation
constricts
Stimulates
Inhibits
Cyclic AMP
In target cells
Cyclic AMP
In target cells

28. Leukotrienes(LTs)
• They are a family of conjugated trienes
formed from eicosanoic acids in
leukocytes,mast cells and macrophages
by lipoxygenase pathway in response to
immunologic and non inflammatory stimuli.
• They have no ring in their structure but
have three conjugated double bonds.

29. Mechanism Of Synthesis of
Leukotrienes
lipoxygenase
5 –Hydroperoxy eicosa tetra – enoic acid(5HPETE)
O2
Arachidonic acid
H20
LeukotrieneA4
GSH
Leukotriene C4
Glutamate
Leukotriene B4
Glycine
Leukotriene E4

30. Functions Of Leukotrienes
• LTs act as mediators of inflammation and
anaphylaxis.
• Elicits erythema and wheal and flare reaction
and increases vascular permeability.
• Inhalation of LTs causes bronchospasm.
• LTs-C4 and D4 are potent stimulators of mucus
secretion.
• LTs- B4 stimulate chemotaxis (movement) of
neutrophils and eosinophils which are found at
the site of inflammation.

31. Lipoxins
• They are a group of compounds produced
by leukocytes.
• They are conjugated tetraenes.
• They are formed by the combined action
of more than one lipoxygenase.
• Lx A4 is the most common type, it is
chemotactic in nature.

32. Thank You