PROSTAGLANDINS,THROMBOXANES & LEUCOTRIENES

Diet
(Fish oils)

COO-

COO

-Linolenate

Eicosapentaenoic acid
COO-

Arachidonate
6.2.1.15
CO.SCoA

Arachidonyl-CoA

CH2OR

CO. 'OCH

O O-

OH OH

CH2OR HOCH O OCH2O PO

OH OH

CH2O PO HO OH

Histamine Adrenaline Thrombin etc.

Phosphatidyl inositol

OH

HO OH OH

Lysophosphatidylinositol

Steroidal Anti-inflammatory Drugs

Phospholipase A2 3.1.1.4
COOOH OH COO-

Arachidonate 2O2 Non-steroidal Anti-inflammatory Prostaglandin Drugs synthase

1.13.11.12

Leucotriene B4
COOOH O

eg. Aspirin
O O

5.3.99.3
COO-

Prostaglandin PGH2
O COOOH

OH

5.3.99.4

OH

OH

Prostacyclins
OH COOHO O OH

Prostaglandin PGE2

OH

5.3.99.5

Thromboxane B2

ENDOPLASMIC RETICULUM

Prostaglandins and the other related eicosanoids are localised, almost ubiquitous, and transient "hormones" involved in a variety of physiological effects which can have very differing and even converse activities in differing tissues. These

include involvement in inflammatory reactions such as rheumatoid arthritis, in the control of blood pressure,
in blood clotting, in the induction of labour or in the aggravation of pain and fever. Arachidonic acid arises from g -linolenic acid an essential lipid which must be obtained from the diet. It is then metabolised to become an acyl group in phospholipids (especially phosphatidylinositol) which are part of the membrane of the endoplasmic reticulum, from whence it is released as the free arachidonic acid by phospholipase A2. This enzyme is activated by a variety external stimuli such as adrenaline, histamine, or thrombin, and is inhibited by corticosteroids and other so-called Steroidal Anti-inflammatory Drugs which thus prevent the re-formation of arachidonic acid - the precursor of prostaglandin. The oxidative cyclisation of arachidonate into prostaglandins takes place in the lumen of the endoplasmic reticulum by the prostaglandin synthase complex which has cyclooxygenase and peroxidase components, the former of which can be inhibited by aspirin and other non-steroidal anti- inflammatory drugs The reaction by which Prostaglandin is formed from arachidonic acid is one of the great "hidden treasures " of metabolism which gives a very satisfying explanation of one of the most universal of drug therapies - why does aspirin relieve headaches - and worse? ENZYMES
1.13.11.12 3.1.1.4 5.3.99.3

of

Lipoxygenase Phospholipase A2 Prostaglandin E synthase

5.3.99.4 5.3.99.5 6.2.1.15

Prostacyclin synthase Thromboxane A synthase Arachidonate-CoA ligase

Designed by Donald Nicholson

c 2002 IUBMB