(PROTEIN) WATER MOLECULE AMINO GROUP

184 • Biochemistry of the Eye
Figure 6–19
Some eicosanoid synthetic pathways.
➤ Numerous pathways exist for the synthesis
of a variety of eicosanoids. Shown
are relevant pathways for the eicosanoids
discussed in the text. Arachidonic
acid, freed from its membrane
phospholipid component by phospholipase
A, is converted to prostaglandin H 2
by the action of cyclooxygenase (prostaglandin
synthase) as shown in the right
hand pathway. Cyclooxygenase, along
with other prostanoid isomerases, is
present in the cellular smooth endoplasmic
reticulum. Note that cyclooxygenase
is inhibited by nonsteroidal antiinflammatory
agents such as aspirin. In
the nomenclature for prostaglandins, PG
stands for prostaglandin while the letters
following such as H, E, and F refer to the
different types of oxygen substitution on
the cyclopentane ring on the left of the
compound. The number 2 refers to
the presence of two double bonds in the
compound. In the left-hand pathway, the
hydroxytetranenoic and hydroxytrienoic
acids (HETE and HETrE) are formed by
the action of cytochrome P-450, monooxygenases.
They may also be synthesized
by lipoxygenases. Both enzymes
are also located in the smooth endoplasmic
reticula of the cell and none of
them are inhibited by anti-inflammatory
drugs.
The physiological effects produced by these hormones, as with the
endocrine hormones, are quite varied. They include control of ionic
composition of the blood and blood pressure, modulation of lung functions,
influence on cell proliferation, control of the inflammatory reaction
(Chapter 9), mediation of gastrointestinal functions, wound healing,
and even control of endocrine functions themselves (Watkins et al,
1989). In the eye, eicosanoids are known to affect the function of virtually
every ocular tissue (Bito, Stjernschantz, 1989). The principal synthetic
pathways important to the eye for the prostaglandins are shown in
Figure 6–19. However, the detailed mechanisms of many of the functions
of these prostaglandins in the eye have not yet been adequately
described. One important observation has been that prostaglandin F2
alpha (PGF 2α) is able to lower the intraocular pressure of the eye (see, for
example, Bito and Baroody, 1989). However, the mechanism for this
action has not described although it has been isolated to the uveoscleral
outflow. Moreover, the use of derivatives of this prostaglandin to treat
glaucoma have been frustrated by the presence of side effects attributed
PLASMA MEMBRANE
PHOSPHOLIPID
PHOSPHOLIPASEA2
(inhibited by steroids)
CYTOCHROME
P-450 FAMILY
(MONO0XYGENASES)
HO
HO
12-HETE
12-HETrE
COOH
COOH
COOH
ARACHIDONIC ACID
OH
OH
ISOMERASE
OH
PGF2
O
O
COOH
CYCLOOXYGENASE
(inhibited by NSAIDS)
ISOMERASE
O
OH
OH
PGH2
OH
PGE2
COOH
COOH