MSc Medical Biochemistry, Ph.D,.
METABOLISM OF UNSATURATED FATTY
ACIDS AND EICOSANOIDS
Animals have limited ability in desaturating fatty acids.
Dietary intake of certain polyunsaturated fatty acids
derived from a plant source is necessary.
These essential fatty acids give rise to eicosanoic (C20)
fatty acids, from which are derived families of
compounds known as eicosanoids.
Eicosanoids include prostaglandins, thromboxanes,
leukotrienes, and lipoxins.
Some polyunsaturated fatty acids
Double bonds are present in cis-configuration.
Palmitoleic and oleic acids are not essential in the diet,
because the tissues are capable of introducing a double
bonds at the 9∆ position into the corresponding fatty
In most mammals, double bonds can be introduced at
the 4, 5, 6,∆ ∆ ∆ and 9∆ positions but never beyond
the ∆9 position.
Linoleic and α-linolenic acids are known as
nutritionally essential fatty acids. Arachidonic acid
can be formed from linolenic acid in most mammals.
Monounsaturated fatty acids are synthesized by
a ∆9 desaturase system:
Several tissues including the liver is responsible for
formation of monounsaturated fatty acids from
saturated fatty acids.
∆9 desaturase system in the endoplasmic reticulum
will catalyze conversion of palmitoyl-CoA or stearoyl-
CoA to palmitoleoyl-CoA or oleoyl-CoA,
The enzyme appear to be similar to cytochrome b5,
and consists of three component proteins, NADH-
cytochrome b5 reductase, cytochrome b5, and a
cynamide-sensitive desaturase containing non-heme
fatty acids involves desaturase
and elongase enzyme systems
In higher animals, additional double bonds are introduced
between the existing double bond and the carboxyl group.
However, in plants they are introduced between the
existing double bond and the ω (methyl terminal) carbon.
Desaturation and chain elongation
system is greatly diminished in the
fasting state, upon glucagon and
epinephrine administration, and in the
absence of insulin as in type I diabetes
Deficiency symptoms in the absence of
essential fatty acids from the diet:
Nonlipid diet plus vitamins A and D
Rat ––––––––––––––––––––––––––––––––––– Reduced growth rate
Deficiency syndrome was cured by the addition of linoleic, α-linolenic, and
arachidonic acids to the diet.
Essential fatty acids are found in structural lipids of the cell and are
concerned with structural integrity of mitochondrial membrane.
Arachidonic acid is present in membranes and accounts for 5-15% of the
fatty acids in phospholipids.
Docosahexaenoic acid (DHA; ω3, 2:6) which is synthesized from α-linolenic
acid or obtained directly from fish oils, is present in high concentrations in
retina, cerebral cortex, testis, and sperm. DHA is needed for development of
the brain and retina and is supplied via the placenta and milk.
Patients with retinitis pigmentosa have low blood levels of DHA. Premature
infants have a low ∆4 desaturase ability, reducing their potential for
synthesizing DHA from n-3 fatty acids precursors.
In essential fatty acid deficiency, nonessential polyenoic acids of the w9
family replace the essential fatty acids in phospholipids, particularly with
The triene:tetraene ratio in plasma lipids can be used to diagnose the extent
of essential fatty acid deficiency.
These fatty acids are found in high concentrations in vegetable oils.
Trans-fatty acids compete with cis-fatty acids
Large amonuts of trans-unsaturated fatty acids in partially
hydrogenated vegetable oils (e.g., margarine) raises the
question of their safety as food additives. They are
metabolized more like saturated than like the cis-
unsaturated fatty acids.
Up to 15% of tissue fatty acids are in trans configuration.
Trans-polyunsaturated fatty acids do not possess essential
fatty acid activity and may antagonize the metabolism of
essential fatty acids and enhance essential fatty acid
Trans-fatty acids raise plasma LDL levels and lower HDL
Formed from C20 polyunsaturated fatty acids
Arachidonate and some other C20 give rise to eicosanoids;
prostaglandins (PG), thromboxanes (TX), leukotrienes (LT),
and lipoxins (LX).
Eicosanoids are pharmacologically and physiologically
Act as hormones functioning through G-protein linked
receptors to elicit their biochemical effects.
Prostaglandin H synthase (PGHS) and two molecules of
There are two PGHS isoenzymes, PGHS-1 and PGHS-2.
Each isoenzyme has cyclooxygenase and peroxidase
Each cell type produces only one type of prostanoid.
"Switching off" of prostaglandin formation is partly achieved
by self-catalyzed destruction, i.e., it is a "suicide enzyme."
Aspirin , a nonsteroidal anti-inflammatory drug (NSAID),
inhibits cyclooxygenase of both PGHS-1 and PGHS-2 by
Most other NSAIDs, such as indomethacin and ibuprofen,
inhibit cyclooxygenases by competing with arachidonate.
Transcription of PGHS-2 but not of PGHS-1 is completely
inhibited by anti-inflammatory corticosteroids.
–Produce leukotrienes from eicosanoic acids in
leukocytes, mastocytoma cells, platelets, and macrophages
in response to both immunologic and nonimuunologic
CLINICAL ASPECTS:Infants receiving formula diets low in fat developed skin symptoms that were
cured by giving linoleate.
Patients maintained for long periods exclusively by intravenous nutrition low
in essential fatty acids. It can be prevented by an essential fatty acid intake
of 1-2% of the total caloric requirement.
Abnormal metabolism of essential fatty acids has been noted in cystic
fibrosis, acrodermatitis enteropathica, hepatorenal syndrome, Sjogren-
Larsson syndrome, multisystem neuronal degeneration, Crohn's disease,
cirrhosis and alcoholism, Zellweger's and Reye's syndrome.
Thromboxanes are synthesized in platelets and upon release cause
vasoconstriction and platelet aggregation. Their synthesis is inhibited by
CLINICAL ASPECTS (cont.)Prostaglandins (PGI2) are produced by blood vessel walls and are
potent inhibitors of platelet aggregation.
Greenland Eskimos have low incidence of heart disease probably
due to high intake of fish oils containing 20:5 ω3 (EPA, or
eicosapentaenoic acid), which gives rise to the series 3
prostaglandins (PG3) and thromboxanes (TX3). PG3 and TX3
inhibit the release of arachidonate from phospholipids and the
formation of PG2 and TX2.
Mixture of leukotrienes C4, D4, and E4 are 100-1000 times more
potent than histamine or prostaglandins as a constrictor of the
bronchial airway musculature.
Leukotrienes are vasoactive, and 5-lipoxygenase has been found
in arterial walls.