8.5.1 Prostaglandins and Thromboxanes8.5.1.1 Prostaglandins: Structure and Biosynthesis
The biosynthesis of prostaglandins and thromboxanes starts from arachidonic acid.
Arachidonic acid, obtained from its phospholipid form by the action of phospholipase A,
is cyclized to prostaglandin endoperoxide (8.63) in the form of PGG (a side-chain per-
oxide), from which PGH 2 (a side-chain hydroxyl) is obtained. Interleukin-1, a cytokine
(see chapter 6) produced by leukocytes and possessing multiple immunological roles,
mediates inflammation by increasing phospholipase activity and thus prostaglandin
synthesis. The first reaction in prostaglandin biosynthesis is catalyzed by PG cyclooxyge-
nase in the presence of O 2 and heme. The second reaction requires tryptophan, probably
as a source of electrons.
The biosynthetic pathway is given in figure 8.9. The endoperoxide PGH 2 then
undergoes a variety of rapid changes. It can be isomerized to the various ketol deriva-
tives, the so-called “primary” prostaglandins designated PGD 2 , PGE 2 , and PGF 2. The
endoperoxide is also transformed into the extremely unstable and potent thromboxane
A 2 (8.64, TXA 2 ) in blood platelets (thrombocytes). This compound has a half-life of
only about 30 seconds, and its isolation and characterization were therefore an experi-
mentaltour de forceof the Samuelsson group. Thromboxane A 2 is rapidly inactivated
to the stable but inactive TXB 2.
Another and equally important substance produced from the endoperoxide is prosta-
cyclin (8.65, PGI2), which is synthesized in the walls of blood vessels. It has an addi-
tional tetrahydrofuran ring which is easily opened and deactivated. Prostacyclin has a
half-life of less than 10 minutes.
Prostaglandins, prostacyclin, and thromboxane are considered autocoids, synthesized in
many different organs and acting locally. They are not stored like neurotransmitters or con-
ventional hormones but are continuously synthesized and released immediately into the
circulation, where they are usually deactivated after only one passage through the lungs.
The synthesis depends on the availability of the starting material, arachidonic acid, and is
modulated by cAMP. Prostaglandin A, PGB, and PGC are inactive degradation products.
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