388
chapter is
Lipids I: Fatty Acids and Eicosanoids
synthesized from the respective saturated fatty acid
coenzyme-A esters. Desaturase is a monooxygenase sys-
tem present in endoplasmic reticulum of liver and adipose
tissue. The overall reaction for palmitoleic acid synthesis
is
Palmitoyl-CoA + NAD(P)H + Hf + 0
2
—
palmitoleyl-CoA + NAD(P)+ +
2
H
2
O
One molecule of oxygen accepts two pairs of electrons,
one from palmitoyl-CoA and the other from NADPH
or NADH. The electrons NAD(P)H are transported via
cytochrome-b
5
reductase to cytochrome bs (microsomal
electron transport; Chapter 14). An enzyme-bound su-
peroxide radical is responsible for the oxidation of acyl-
CoA. Four desaturases specific for introducing cis dou-
ble bonds at C
9
, C
6
, C5, and C
4
, respectively, are known.
If the substrate is saturated, the first double bond intro-
duced is C
9
. With an unsaturated substrate, other dou-
ble bonds are introduced between the carboxyl group and
the double bond nearest the carboxyl group. Desatura-
tion yields a divinylmethane arrangement of double bonds
(—CH=CH—CH
2
—CH=CH—). Usually desaturation al-
ternates with chain elongation. Desaturation is inhibited
by fasting and diabetes. The oxidation of unsaturated fatty
acids occurs in mitochondria.
18.7
trans
-Fatty Acids
trnns
-Fatty acid metabolism is similar to that of saturated
fatty acids. During the partial dehydrogenation of veg-
etable oils (e.g., in the manufacture of margarine), the cis
fatty acids are isomerized to
trans-fatty
acid forms. The
“hydrogenated” margarines contain 15^40% of
trans
-fatty
acids.
The hypercholesterolemic effect of
trans
-fatty acids
may be due to impairment of the first step in the for-
mation of bile acids from cholesterol. Since the steady-
state level of cholesterol depends on its conversion to
bile acid (Chapter 19), any perturbation in this process
affects cholesterol levels. Both metabolic and epidemio-
logical studies have shown that the consumption of
trans-
fatty
acids increases the risk of coronary heart disease.
This risk appears to be even higher when compared on
a per-gram basis with saturated fatty acids. The adverse
effects of
trans-fatty
acids are attributed to the elevation
of atherogenic low-density lipoprotein (LDL) cholesterol
and a decrease in the antiatherogenic (or cardioprotective)
high-density lipoprotein (HDL) cholesterol level. Thus,
the ratio of LDL cholesterol to HDL cholesterol is signif-
icantly higher with the
trans
-fatty acid diet compared to
a saturated-fat diet. A diet rich in oleic acid has a lower
ratio of LDL cholesterol to HDL cholesterol compared
to either of the other diets. The metabolism of lipopro-
teins and their role in atherosclerosis are discussed in
Chapter 20.
18.8 Essential Fatty Acids
Polyunsaturated fatty acids not synthesized in the body but
required for normal metabolism are essential fatty acids
(EFAs). EFAs are linoleic acid, linolenic acids (a and
y),
and arachidonic acid. All contain at least one double bond
located beyond C-9 or within the terminal seven carbon
atoms (Table 18-3).
cu-Carbon
\ , 1
2
3
4
5
6
7
8
H3C — C H 2— C H 2— C H 2— C H 2— C H 2— C H 2— C H 2— (CH 2)„— COOH
v
____/ ^---—
---
- -v
Introduction of double bonds
Double bonds
does not occur in humans
can be
introduced in
this region
A double bond within the terminal seven carbon atoms
can be present at
to-
3 or cu-
6
.
y
-Linolenic acid is an
00
-
6
EFA and a-linolenic acid an
co-3
EFA. Other
to-3
EFA are
eicosapentaenoic acid (EPA) and docosahexaenoic acid
(DCHA), both abundant in edible fish tissues. Vegetable
oils are rich in
to
- 6
EFA (Table 18-4). Plants contain
a-
linolenic acid, which can be converted in the body to EPA
and DCHA, but it is found within chloroplast membranes
and not in seed oils; hence, it may not be available in
significant quantities in the diet. The
to-
3 and
to
- 6
EFA
have different metabolic effects (see below). Particularly
rich sources of EPA are fishes (e.g., salmon, mackerel, blue
fish, herring, menhaden) that live in deep, cold waters.
These fishes have fat in their muscles and their skin. In
contrast, codfish, which have a similar habitat, store fat in
liver rather than muscle. Thus, cod liver oil is a good source
of EPA, but it also contains high amounts of vitamins A
and D, which can be toxic in large quantities (Chapters 38
and 37, respectively). Shellfish also contain EPA. Plankton
are the ultimate source of EPA.
Linoleic acid can be converted in mammalian liver to
y
-linolenic acid and arachidonic acid by the microsomal
desaturation and chain elongation process (Figure 18-14).
Thus, the requirement for arachidonic acid may be dis-
pensed with when the diet contains adequate amounts
of linoleic acid. Similarly, o;-linolemc acid is converted
by desaturation and chain elongation to EPA and DCHA
(Figure 18-15).
