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chapter 18
Lipids I: Fatty Acids and Eicosanoids
O H
O H
Q H
C O O H
H O
O H
.CO OH
O H
.COOH
C O O H
7 a -Hydroxy-5,11 -diketotetranor-
prostane-1,16-dioic acid
5 a ,7 a -Dihydroxy-11 -ketotetranor-
prostane-1,16-dioic acid
(Both metabolites are inactive and excreted in urine.)
C O O H
C O O H
FIGURE 18-24
Catabolism of PGE
2
and PGF
2
(,. 15-PGDH = I5-Hydroxy-PG-dehydrogenase; I3-PGR= 13-PG-reductase.
levels. Thus, the ratio between E and F compounds (due
to changes in the [NAD+]/[NADH] ratio) may be a cru-
cial factor in control of a given physiological response.
The relative proportions of TXs and leukotrienes, as op-
posed to PGI, also appear to exert an important influence
on physiological response.
In most animal species, PGI
2
, PGEs, and PGAs are va-
sodilators, while TXA
2
is a vasoconstrictor. PGF
2
a and
15-methyl PGF
2
« are used for induction of mid-trimester
abortions because they stimulate uterine muscle. Several
PGs suppress gastric HC1 production, which has therapeu-
tic potential in the treatment of gastric ulceration and may
explain the effect of aspirin to increase HC1 secretion by
inhibition of PG synthesis. PGE
2
elevation causes fever by
increasing firing rates of neurons that control thermoreg-
ulation in the hypothalmus.
The effect of prostanoids on platelets has received con-
siderable interest. TXA
2
synthesized in platelets induces
platelet aggregation, whereas PGI
2
generated in the vessel
wall inhibits platelet aggregation. PGI
3
(Figure 18-17),
a product of eicosapentaenoic acid (an
0 0
-
3 fatty acid),
inhibits TXA
2
synthesis by inhibiting release of arachi-
donate from phospholipids and by competing for throm-
boxane synthase. TXA
3
is a much weaker aggregator of
platelets than is TXA
2
, while PGI
3
is a stronger antiag-
gregator than is PGI
2
. The net effect is an antiplatelet ef-
fect, which may be beneficial in patients with thrombotic
complications (e.g., myocardial infarction). The low in-
cidence of coronary thrombosis in Greenland Eskimos,
whose diet is almost completely derived from marine
sources rich in
co
-3 fatty acids, has been attributed to an-
tiplatelet effects. This diet is also associated with lower
levels of serum cholesterol and triacylglycerol than typical
Western diets.
Leukotrienes
Leukotrienes (LTs) are most commonly found in leuko-
cytes, mast cells, platelets, and vascular tissues of the lung
and heart. They are formed chiefly from arachidonic acid,
