PROSTAGLANDINS

2.  Postaglandins & their related compounds
prostacyclins (PGI), thromboxanes (TXA),
leukotrienes (LT) & lipoxins are collectively
known as eicosaniods, they all contain 20C.
 Structure of prostaglandins:
 Prostaglandins are derivatives of 20-carbon
fatty acid - prostanoic acid, hence known as
prostanoids.

3.  This has a cyclopentane ring (formed by
carbon atoms 8 to 12) & two side chains, with
carboxyl group on one side.
 Prostaglandins differ in their structure due to
substituent group & double bond on
cyclopentane ring.
 Most important prostaglandins (PGF2 &
PGF2α), prostacyclins (PGI2), thromboxanes
(TXA2) & leukotrienes (LTA4).

5.  Arachidonic acid (5,8,11,14 - eicosatetraenoic
acid) is the precursor for most of the
prostaglandins in humans.
 It occurs in the endoplasmic reticulum.
 Release of arachidonic acid from membrane
bound phospholipids by phospholipase A2.
 It occurs due to a specific stimuli by
hormones – epinephrine or bradykinin.

6.  Oxidation & cyclization of arachidonic acid
to PGG2 which is then converted to PGH2 by
peroxidase.
 PGH2 serves as the immediate precursor for
the synthesis of a number of prostaglandins,
including prostacyclins & thromboxane.
 This is known as cyclic pathway of
arachidonic acid.

8.  Cyclooxygenase – a suicide enzyme.
 Prostaglandin synthesis can be partly
controlled by suicidal activity of the enzyme
cyclooxygenase.
 This enzyme is capable of undergoing self-
catalysed destruction to switch off PG
synthesis.

9.  Corticosteroids (e.g. cortisol) prevent the
formation of arachidonic acid by inhibiting
the enzyme phospholipase A2.
 Anti-inflammatory drugs inhibit the synthesis
of prostaglandins, prostacyclins &
thromboxane.
 They block the action of cyclooxygenase.
 Aspirin irreversibly inhibits cyclooxygenase.

10.  All the eicosanoids are metabolized rapidly.
 Degradation occur in lung & liver.
 Two enzymes, namely 15-α-hydroxy PG
dehydrogenase & 13-PG reductase, convert
hydroxyl group at C15 to keto group & then
to C13 and C14 dihydroderivative.

11.  Prostaglandins act as local hormones.
 PGs are produced in almost all the tissues.
 PGs are not stored & they are degraded to
inactive products at the site of their
production.
 PGs are produced in very small amounts &
have low half-lives.

12.  Regulation of blood pressure:
 The prostaglandins (PGE, PGA & PGl2) are
vasodilator in function.
 This results in increased blood flow and
decreased peripheral resistance to lower the
blood pressure.
 PGs serve as agents in the treatment of
hypertension.

13.  Inflammation:
 PGEI & PGE2 induce the symptoms of
inflammation (redness, swelling, edema etc.)
due to arteriolar vasodilation.
 PGs are natural mediators of inflammatory
reactions of rheumatoid arthritis, psoriasis,
conjunctivitis etc.
 Corticosteroids are used to treat these
inflammatory reactions, since they inhibit
prostaglandin synthesis.

14.  Reproduction:
 PGE2 & PGF2 are used for the medical termination of
pregnancy & induction of Iabor.
 Pain and fever:
 Pyrogens (fever producing agents) promote
prostaglandin synthesis leading to the formation of
PGE2 in hypothalamus-regulation of body temperature.
 PGE2 along with histamine & bradykinin cause pain.
 Migraine is also due to PGE2.
 Aspirin & other non-steroidal drugs inhibit PG synthesis
& thus control fever & relieve pain.

15.  Regulation of gastric secretion:
 Prostaglandins (PGE) inhibit gastric secretion.
 PGs are used for the treatment of gastric ulcers.
 PGs stimulate pancreatic secretion & increase
the motility of intestine which often causes
diarrhea.
 Influence on immune system:
 Macrophages secrete PGE which decreases the
immunological functions of B-& T-lymphocytes.

16.  Effects on respiratory function:
 PGE is a bronchodilator whereas PGF acts
as a constrictor of bronchial smooth
muscles.
 PGE & PGF oppose the actions of each other
in the lungs.
 PGEI & PGE2 are used in the treatment of
asthma.

17.  Influence on renal functions:
 PGE increases glomerular filtration rate &
promotes urine output.
 Excretion of Na+ & K+ is also increased by PGE.
 Effects on metabolism:
 Prostaglandins influence certain metabolic
reactions, through the mediation of cAMP.
 PGE decrease lipolysis, increases glycogen
formation & promotes calcium mobilization.

18.  Platelet aggregation & thrombosis:
 The prostaglandins – prostacyclins (PGI2),
inhibit platelet aggregation.
 Thromboxanes (TXA2) & prostaglandin E2
promote platelet aggregation & blood
clotting that might lead to thrombosis.
 Mechanism of action of PGs:
 PGE increases cAMP & PGF increases cGMP.

19.  They are used in the treatment of gastric
ulcers, hypertension, thrombosis, asthma etc.
 Prostaglandins are also employed in the
medical termination of pregnancy,
prevention of conception, induction of labor
etc.

20.  Leukotrienes are synthesized by leucocytes,
mast cells, lung, heart, spleen etc., by
lipoxygenase pathway of arachidonic acid.
 Leukotrienes (A4, B4, C4, D4 & E4) are
synthesized through the intermediate, 5-
hydroperoxyeicosatetraenoic acid (5-HPETE).

22.  Leukotrienes (C4, D4 & E4) are components of
slow-reacting substances of anaphylaxis (SRS-
A), released after immunological challenge.
 SRS-A is 100 -1,000 times more potent than
histamine or prostaglandins in its action as a
stimulant of allergic reactions.
 Leukotrienes are implicated in asthma,
inflammatory reactions, hypersensitivity
(allergy) and heart attacks.

23.  Leukotrienes cause contraction of smooth
muscles, bronchoconstriction,
vasoconstriction, adhesion of white blood
cells & release of lysosomal enzymes.
 Lipoxins are involved in vasoactive &
immunoregulatory functions.

24.  Textbook of Biochemistry – U Satyanarayana