8/3/2019 34. Prostaglandins
1/1
-Linolenate
Arachidonate
OH
OH
O
O
O
HOOH
Prostaglandin PGE2
Prostaglandin PGH2
OHOH
O
Phospholipase A2
Anti-inflammatoryNon-steroidal
Anti-inflammatorySteroidal
Drugs
Drugs
Arachidonate
Arachidonyl-CoA
COO
OH OH
HO
OH
OH
O'OCH
O-
CHOR2
CHO PO2
CO.SCoA
CO.
Diet
Lysophosphatidylinositol
OH OH
HO
OH
OH
OHOCH
O-
CHOR2
CHO PO2
Leucotriene B42O2
OHOH
OOH
OHOH
Thromboxane B2
Eicosapentaenoicacid
(Fish oils)
PROSTAGLANDINS,THROMBOXANES & LEUCOTRIENES
Prostaglandinsynthase
Prostacyclins
eg. Aspirin
6.2.1.15
3.1.1.4
5.3.99.5
5.3.99.4
1.13.11.12
5.3.99.3
COO-
COO-
COO-
COO-
COO- COO-
COO-
COO-
Phosphatidyl inositol
6.2.1.15 Arachidonate-CoA ligase
ENZYMES
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 -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
of
external stimuli such as adrenaline, histamine, or thrombin, and
is inhibited by corticosteroids and other so-calledSteroidal
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?
ENDOPLASMIC RETICULUM
HistamineAdrenaline
Thrombin
etc.
g
1.13.11.12 Lipoxygenase3.1.1.4 Phospholipase A2
5.3.99.3 Prostaglandin E synthase
5.3.99.4 Prostacyclin synthase5.3.99.5 Thromboxane A
synthase
