section 18.9
Metabolism of Eicosanoids
Deficiency of Essential Fatty Acids
The clinical manifestations of EFA deficiency in humans
closely resemble those seen in animals. They include dry,
scaly skin, usually erythematous eruptions (generalized or
localized and affecting the trunk, legs, and intertriginous
areas), diffuse hair loss (seen frequently in infants), poor
wound healing, failure of growth, and increased metabolic
rate. Abnormalities in ECG patterns may be due to mem-
brane alterations, which may also account for structural
and functional abnormalities observed in mitochondria.
Surgical patients maintained on glucose-amino acid solu-
tions for prolonged periods develop EFA deficiency, man-
ifested as anemia, thrombocytopenia, hair loss and sparse
hair growth, increased capillary permeability, dry scaly
skin, desquamating dermatitis, and a shift in the oxygen-
dissociation curve of hemoglobin to the left. Oral or in-
travenous administration of linoleic acid is necessary to
correct these problems. Fat emulsions containing linoleic
acid are commercially available for intravenous use. An
adult requires 10 g of linoleic acid per day. The recom-
mended dietary allowance for EFA is 1-2% of the total
energy intake.
EFA deficiency can also occur in infants with highly re-
stricted diets (e.g., primarily skim milk intake), in patients
receiving total parenteral hyperalimentation without sup-
plements of unsaturated lipids, and in those with severe
malabsorptive defects.
In EFA deficiency, oleic acid can be dehydrogenated
to yield polyunsaturated fatty acids (PUFAs) that are
nonessential and do not substitute for the essential fatty
acids. One such PUFA is 5,8,11-eicosatrienoic acid, which
occurs in significant amounts in heart, liver, adipose tissue,
and erythrocytes of animals fed diets deficient in EFAs but
decreases after supplementation with linoleic or linolenic
acids. Its appearance in tissues and plasma has been used
in the assessment of EFA deficiency.
Most vegetable oils are relatively rich in EFAs (coconut
oil is an exception), low in saturated fatty acids, and lack
cholesterol. Animal fats (except those in fish), on the other
hand, are generally low in EFAs, high in saturated fats, and
contain cholesterol. The EFA content of body and milk fat
of ruminants can be increased by the feeding of EFA en-
cased in formalin-treated casein. The EFA is released at
the site of absorption by dissolution of the capsules. These
dietary manipulations in ruminants are accompanied by
an increase in carcass EFA, a decrease in saturated fatty
acids, and no change or an increase in cholesterol content.
Table 18-4 summarizes the fatty acid composition of some
fats of animal and plant origin. The recommended daily
diet does not exceed 30-35% of the total energy intake
as fat (current average consumption in North America is
40-45%), with equal amounts of saturated, monounsatu-
rated, and polyunsaturated fats, and a cholesterol intake of
no more than 300 mg/day (current average consumption
in North America is about 600 mg/day).
Substitution of
polyunsaturated for saturated fats in
the diet lowers plasma cholesterol levels through reduction
in levels of VFDF and FDF. Diets rich in polyunsaturated
fats lead to higher biliary excretion of sterols, although
this effect may not be directly related to reduced levels
of plasma lipoproteins. Diets low in EFA (linoleic acid)
have been associated with high rates of coronary heart
disease. A significantly lower proportion of EFA in the
adipose tissue of people dying from coronary heart dis-
ease has been reported, and an inverse relationship has
been found between the percentage composition of EFA
in serum cholesteryl esters and mortality rates from coro-
nary heat disease. Consumption of
fatty acids markedly decreases plasma triacylglycerol and,
to a lesser extent, cholesterol levels in some hyperlipopro-
teinemic patients (Chapter 20). Consumption of fish-oil
fatty acids decreases the biosynthesis of fatty acids and
of VFDF by the liver and also decrease the platelet and
monocyte function. These effects of a>-3 fatty acids appear
to prevent or delay atherogenesis. Fow death rates from
coronary heart disease are found among populations with
high intake of fish (e.g., Greenland Eskimos, people of
fishing villages of Japan, people of Okinawa). Metabolic
and functional differences exist between
acids. They have opposing physiological effects and their
balance in the diet is important for homeostasis and normal
18.9 Metabolism of Eicosanoids
The eicosanoids
), prostacyclins
(PGIs), and
derived from essential fatty acids and act similarly to hor-
mones (Chapter 30). However, they are synthesized in al-
most all tissues (unlike hormones, which are synthesized
in selected tissues) and are not stored to any significant
extent; their physiological effects on tissues occur near
sites of synthesis rather than at a distance. They function
as paracrine messengers and are sometimes referred to as
The four groups of eicosanoids are derived, respec-
tively, from a
2 0
-carbon fatty acid with three, four, or
five double bonds: 8,11,14-eicosatrienoic acid (dihomo-
y-linolenic acid), 5,8,11,14-eicosatetraenoic acid (arachi-
(Figure 18-17). In humans, the most abundant precursor
is arachidonic acid. Secretion of eicosanoids in response
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