Eicosanoids

Eicosanoids are a family of very potent biological

signaling molecules that act as short-range messengers
(affecting tissues near the cells that produce them) In
response to hormonal or other stimuli,
Mammals have two isozymes of prostaglandin H2 synthase,
COX-1 and COX-2.
These have different functions but closely similar amino acid
sequences and similar reaction mechanisms at both of their
catalytic centers.
COX-1 is responsible for the synthesis of the prostaglandins
that regulate the secretion of gastric mucin, and COX-2 for the
prostaglandins that mediate inflammation, pain, and fever.
 Synthesis
Phospholipase A 2 ,present in most types of mammalian
cells, attacks membrane phospholipids, releasing
arachidonate from the middle carbon of glycerol

Bifunctional enzyme, cyclooxygenase (COX), also called

prostaglandin H 2 synthase convert arachidonate to PGH2 in
2 steps
Cyclooxygenase introduces molecular oxygen to convert
Arachidonic Acid Synthesis in
Eukaryotes.
Arachidonic acid is
synthesized from linoleic
acid in eukaryotes.
This is the means by
which animals synthesize
fatty acids with double
bonds at positions other
than C-9.
Mammals have 4, 5, 6
and 9 desaturases.
PGH2 Synthesis

202
 Medical importance
Aspirin irreversibly inactivates the cyclooxygenase
activity of COX by acetylating a Ser residue and
blocking the enzymes active site, thus inhibiting the
synthesis of prostaglandins and thromboxanes.
Ibuprofen, a widely used nonsteroidal
antiinflammatory drug (NSAID) inhibits the same
enzyme.
3 and 6 Essential Fatty Acids
with Many Functions

Linoleic acid and linolenic acid are termed

essential fatty acids because animals cannot
synthesize them and must acquire them in their
diet.
Linoleic acid is the precursor of arachidonic acid
and both of these are termed 6 fatty acids.
Linolenic acid is the precursor of eicosapentaenoic
acid and docosahexaenoic acid and these three
are termed 3 fatty acids.
3 fatty acids are cardioprotective, anti-
inflammatory, and anticarcinogenic.
6 fatty acids are precursors of prostaglandins,
thromboxanes, and leukotrienes (