Polyunsaturated Fatty Acids

Introduction
Chemistry of PUFAs
Metabolism and Fate of PUFAs
Oxidation of PUFAs
Biological Effects of PUFAs
Biomedical Importance
References
Introduction
Polyunsaturated fatty acids necessary for body as components of cellular membrane
Also as precursors for synthesis of eicosanoids
PUFAs itself have role in mediating gene expression according to recent research and
studies
Dietary PUFAs significance has been increasingly noticed and extensively researched
Chemistry of PUFA
Fatty acids with two or more double bonds in cis configuration
Important two families of PUFA omega 3 & omega 6
Linoleic acid -6 & linolenic acid -3
Also known as dietary essential fatty acids (EFAs)
Chemistry of PUFAs
Double bonds in PUFAs almost never conjugated (alternating single & double bonds ,
as in CH=CHCH=CH )
Separated by a methylene group CH=CH CH2CH=CH
Nearly all naturally occurring unsaturated fatty acids, double bonds are in cis configuration
More kinks in fatty acid chain
Unsaturated fatty acids form two different shapes
PUFAs Must Be Obtained From
Diet
Human can synthesize monounsaturated fatty acids
By action of 9 desaturase system
Lack enzymes system to form double bonds beyond C 9
Cannot synthesize linoleic acid (LA), 18:2( 9,12 ), or -linolenic acid (ALA), 18:3(
9,12,15 )

 Starting points for the synthesis of a variety of other polyunsaturated fatty acids
Necessary for synthesis of important products in body
Sources of PUFAs
Omega 6 fatty acids vegetable oils
Omega 3 fatty acids fish oils
Metabolism of PUFA
Ultimate source of PUFAs from diet
In body, dietary essential fatty acids undergo some modification (desaturation & elongation)
Human can introduce double bonds at 4,5,6, and 9 positions by ER membrane bound
desaturase system
Once modified stored in cell membranes esterified at glycerol C2 of phosphatidylinositol
and other phospholipids
Desaturation & Elongation System
is Greatly Diminished in
Fasting state
Glucagon and epinephrine administration
Type I diabetes mellitus (lack of insulin)
Desaturation & Elongation System is Induced in
Regular exercise & physical training >>>Oxidation of PUFAs
Excess polyunsaturated fatty acids are degraded by oxidation
Modified steps included in oxidation
Odd-numbered double bonds are handled by the isomerase, and even-numbered ones by the
reductase and the isomerase
Long chain PUFAs (C20,C22) undergo peroxisomal FA oxidation
Oxidation of PUFA
Unorthodox Metabolic Route For PUFA Oxidation
PUFA derived from membrane phospholipids can undergo auto-oxidation in vivo,
generating a complex mixture of hydroperoxides, epoxides and cyclic peroxides
Epoxides of PUFA can be formed by autooxidation, by cytochrome P450 and possibly by
the oxidative burst of inflammatory cells
Epoxides of ALA are toxic
5,6-epoxide of AA is an excellent substrate of COX and thromboxane synthase, with
vascular and renal effects

Eicosanoid Hormones Are Derived From Polyunsaturated Fatty Acids

EFA in the plasma membranes serve as substrates for the enzyme cyclo-oxygenase
(COX) and lipo-oxygenase (LOX)
Arachidonate - major precursor of several classes of signal molecules: prostaglandins,
prostacyclins, thromboxanes, and leukotrienes
Production of arachidonate metabolites is controlled by the rate of arachidonate release
from the phospholipids through other alternative pathways such as Cyclooxygenase Pathway
and Lipoxygenase Pathway
Biological Effects of PUFAs
LA is a structural component in the ceramides of the water barrier of the skin
Kinks in fatty acid chain modulates membrane fluidity thereby affecting membrane
permeability
Increasing evidence points to a specific role of DHA in membrane function, especially in
retina and in neuronal tissues
AA is a precursor of group 2 eicosanoids
EPA and DHA serve as a precursor for n-3 eicosanoids
Metabolites of EPA, DHA and AA have competitive functions: i.e., ingestion of EPA and
DHA from fish or fish oil replaces AA from membrane phospholipids in practically all cells
Eicosanoids from AA are biologically active in small quantities and, if formed in large
amounts, contribute to the formation of thrombi and atheromas, the development of allergic
and inflammatory disorders, and cell proliferation
PG
3 & TX3 derived from EPA inhibit release of arachidonate from phospholipids and formation
of PG2 and TX2
Eicosanoids derived from AA and EPA have very similar molecular structures but markedly
different biologic effects
EPA-derived eicosanoids (prostaglandins of the 3 series and leukotrienes of the 5 series) are
in general much less potent inducers of inflammation than the AA-derived eicosanoids
Some Important Eicosanoids
TX - synthesized in platelets, causes vasoconstriction and platelet aggregation
SRS-A is a mixture of (LT C4,D4&E4) potent bronchoconstriction, increased vascular
permeability,

attraction

and

activation

of

leukocytes,

immediate

hypersensitivity

reactionasthma
Lipoxins - anti-inflammatory role in vasoactive and immuno-regulatory function

Epigenetic Properties of PUFA

PUFA elicit changes in gene expression
Occurred within a matter of minutes
5 flanking regions of genes encoding carnitine palmitoyltransferase, acyl-CoA oxidase,
mitochondrial HMG-CoA synthase, fatty acylCoA synthetase and mitochondrial uncoupling
proteins all contain DNA recognition sequences for PPAR
PUFA are potent PPAR activators
PUFAs significantly increases and the induction of genes associated with higher rates of fat
oxidation and reduced body fat deposition
In animal models n-6 and n-3 PUFA are potent inducers of fatty acid oxidation and potent
suppressors of fatty acid and triacylglycerol synthesis
EPA binds to PPAR- reducing lipid levels in muscle and adipose tissue and improves
insulin sensitivity in these tissues
n-3 PUFAs have significant effects on insulin sensitivity in various tissues, particularly
skeletal muscle
PUFA-mediated induction of PPAR- regulated genes shifts hepatic metabolism away
from lipid synthesis and storage toward lipid oxidation
prevents lipotoxicity associated with lipid overload
Hydrogenation of PUFA
Conversion of PUFA to MUFA then SFA
Processed food
Production of solid fat from oils
Production of more chemically stable fats (resists oxidation & rancidity)
Trans UFA
Trans fats mainly found in foods with partially hydrogenated fats
Several studies show association between consumption of trans fats and risk of coronary
heart disease
Increased consumption of trans fats increase LDL-C, possibly by decreasing LDL receptor
activity
High dietary intake of trans fatty acids interfere with the desaturation and elongation of LA
and LA and thus lower AA, EPA, and DHA concentrations
Assessment of PUFA status
If insufficient essential PUFA are available to meet PUFA requirements, the body starts to
synthesize certain fatty acids that are hardly present if the EFA and PUFA status is adequate

 Best known marker is Mead acid (C20:3n-9)

Presence of Mead acid indicates a general shortage of all essential PUFA
Biomedical Importance
High intake of n-6 PUFA experimentally associates with colonic cancer, breast cancer,
tumor initiation, promotion, cell proliferation, tissue invasion, & metastatic spread
High dietary ratio of n-6 to n-3 PUFAs associated with increased cardiovascular incidents
Essential Fatty Acids Deficiency
Primarily deficiency of n 6 PUFAs, which are required in substantially larger quantities than
n3 PUFAs
Usually present with skin rash & alopecia
Usually found in patients depending on parenteral nutrition, EFA deficient formula fed
infants
Omega 3 Fatty Acids Deficiency

Synthesis

of

phospholipids

containing

the

highly polyunsaturated

fatty acid

docosahexaenoic acid (22:6 n 3 or DHA) is critical for normal brain development and retinal
function
DHA is the most abundant polyunsaturated fatty acid in the central nervous system
DHA shown to modulate phosphatidylserine biosynthesis and neuronal signaling
Excess consumption of n-6 PUFAs affect DHA synthesis