Eicosanoids

Eicosanoids
• They are derived from 20 carbon- arachidonic
acid

• They act as local hormones- G-protein coupled

receptors

• Prostaglandins, Thromboxanes, Leukotrienes

& Lipoxins
 Membrane Phospholipid

Phospholipase A2 inhibited by glucocorticoids

Arachidonic acid Leuokotrienes

Cyclooxygenase Lipoxygenase

inhibited by aspirin,
ibuprofen

PGH2 Thromboxanes in
platelets

Prostaglandins in many cells

Figure 4. Conversion of arachidonic acid to eicosanoids.

 Prostaglandins
• There are 3 series of PG’s
Series 1- linolenic acid
Series 2- arachidonic acid (naturally occuring)
Series 3- timnodonic acid

• PG’s are formed at the site of action

• They are not stored
 Prostaglandins
• Cyclooxygenase pathway is reponsible
for PG and thromboxane(TXA)
synthesis
• Prostaglandin H synthase(PGHS)- has 2
enzyme activities – cyclooxygenase &
peroxidase
• PGHS – 2 isoenzymes
 Prostaglandins
• PGHS 1- ( COX-1) – constitutive- present in all
cells-gastric , renal & platelets function

• PGHS 2- ( COX-2) – inducible- inflammatory

response

• The cyclooxygenase enzyme is short lived &

rapidly inactivated; prevents excess production
of PG
 Some Functions of Prostaglandins

PGI2, PGE2, PGD2

• ↑ Vasodilation, cAMP, bronchodilation
• ↓ Platelet and leukocyte aggregation, IL1 and
IL2, T-cell proliferation, lymphocyte migration
PGF2a
• ↑ Vasoconstriction, Bronchoconstriction,
smooth muscle contraction
TXA2
• ↑ Vasoconstriction, Platelet aggregation,
lymphocyte proliferation, bronchoconstriction
 Therapeutic uses of Prostaglandins
• PG F2- used in induction of labour, arresting
postpartum haemarrhage
• PG E2- broncho dilator- bronchial asthma
• PG I2- used for pulmonary hypertension
• PG – inhibit gastric secretion& increase gastric
motility- used in peptic ulcer
 Drugs to decrease inflammation
• Glucocorticoids
Drugs to decrease inflammation
 Aspirin
• Irreversibily inhibits cyclooxygenase( COX-1 & 2)

• Acetylation of Serine residue in its active site

• decreased TXA2---in platelets-  inhibits

platelet aggregation & decreased
vasoconstriction

• used in prevention of heart attacks

 Other NSAIDS
• Ibuprofen, Indomethacin, Diclofenac

• Act by irreversibly inhibiting cyclooxygenase

• Compete with arachidonic acid

 Paracetamol
• Reversible inhibitor of cyclooxygenase
 Leukotrienes

• Lipoxygenase pathway

• produced in leukocytes, platelets &

macrophages

• Activate immune response- involved in

chemotaxis, inflammation & allergic reactions
 Fatty Liver
• Due to excess accumulation of fat in the
liver( hepatic steatosis)
 Fatty Liver
• Increased uptake of FA & reduced clearance of
FA----- FATTY LIVER

• when liver is laden with excess fat, their

metabolic activity is impaired

• Necrosis- Fibrosis- CIRRHOSIS

 a. Excess Fat deposition in Liver
• Increased mobilisation of FA from adipose
tissue in DM & starvation

•
 a. Excess Fat deposition in Liver
• Excess synthesis of FA from excess intake of
dietary glucose

•
 b. Reduced removal of fat from Liver
• Toxic injury to liver- CCl4, arsenic, lead

• Protein Energy Malnutrition & Hepatitis B

infection- Reduced synthesis of apoproteins-
apoB100 & apo C- -- decreased VLDL--
reduced clearance of fat from liver
Alcoholic fatty liver
 Lipotropic factors
• Required for normal mobilisation of fats from
liver
• Deficiency-- fatty liver

• Choline
• Lecithin & methionine- syn of apoproteins
• Vitamin E & Selenium-anti-oxidant effect
• Omega 3 fatty acids
Thank you