section 18.9
Metabolism of Eicosanoids
397
M e m b ra n e
P h o sp h o lip id
P h o s p h o lip a s e A
2
A rac h id o n ic A cid
ch
3
5 -lip o x y g e n a s e a n d
a c tiv a to r p ro tein
5 -H P E T E
H
2
5 -lip o x y g e n a s e a n d
G ly — C y s
I
S
S y n th e s iz e d
in e x tra c e llu a r <
s p a c e
S
.
C y stein y l
?
L e u k o trie n e s
LTE,
FIGURE 18-25
Pathway for the biosynthesis of leukotrienes.
but they may be derived from eicosatrienoic and eicos-
apentaenoic acids. The name “leukotrienes” derives from
their discovery in leukocytes and from the conjugated
triene structure they contain. In the most active LTs, the
conjugated triene is in a trans, trans, cis arrangement. They
are distinguished by letters A-E and by a subscript that in-
dicates the number of double bonds present.
LTs are produced in the 5-lipoxygenase pathway
(Figure 18-25). Their synthesis begins with arachidonic
acid obtained from cleavage of the membrane phos-
pholipid pool due to the action of phospholipase A2.
Arachidonic acid is converted in a catalytic sequence
by 5-lipoxygenase complex and its activating protein
to 5-hydroperoxyeicosatetraenoic acid (5-HPETE) and
