Fatty Acids

• Based on length of carbon chains:

1) Short chain – < 8 carbons
2) Medium chain – 10-14 carbons
3) Long chain – 16-24 carbons
• According to number of double bonds between the
carbon atoms
A. Saturated Fatty Acids
B. Unsaturated Fatty Acids
i. Monounsaturated fatty acids
ii.Polyunsaturated fatty acids
 Medium chain fatty acids
• Water soluble
• Transported as free fatty acid, bound to albumin,
through the portal system.
• Digested quickly and not likely to be affected by
intestinal factors that inhibit fat absorption.
• Not stored in the adipose tissue.
• Natural MCT – milk fat, coconut oil, etc.
• Clinically, oils rich in MCTs are used for patients with
o Fat malabsorption
o In catabolic states such as AIDS and cancer.
 PUFA
• Omega and n indicate the distance of the first
bond along the carbon chain.
• ω-6 fatty acids are PUFA- First double bond on
the 6th carbon atom from the methyl end of
the carbon chain.
• Omega -3 and omega – 6 fatty acids are
biologically active.
 CLASSIFICATION OF LIPIDS
1. Simple
2. Complex
3. Derived
4. Miscellaneous
1. SIMPLE LIPIDS: Esters of fatty acids with alcohols.
i. Fats and Oils: Esters of fatty acids with glycerol. Oil –
liquid, Fat – Solid at RT.
ii.Waxes: Esters of fatty acids with alcohols other than
glycerol.
•Most commonly found – cetyl alcohol.
•Used in the preparation of candles, lubricants, ointments,
cosmetics, polishes, etc.
2. COMPLEX/COMPOUND LIPIDS: Esters of fatty acids
with alcohols containing additional groups such as
phosphate, nitrogenous base, carbohydrate, protein, etc.
a) Phospholipids: Alcohol + Fatty acids+ Phosphoric acid
and frequently a nitrogenous base.
i. Glycerophospholipids: contain glycerol as the alcohol.
Ex: Lecithin, Cephalin.
ii. Sphingophospholipids: Sphingosine is the alcohol.
Ex: Sphingomyelin.
b) Glycolipids: Fatty acid +Carbohydrate + Nitrogenous
base. Alcohol is Sphingosine - Glycosphingolipids.
Ex: Cerebrosides, Gangliosides.
c) Lipoproteins: Complexes of lipids with proteins.
c) Other complex lipids: Sulfolipids, aminolipids,
lipopolysaccharides.
3. DERIVED LIPIDS: Derivatives obtained on the
hydrolysis of simple and compound lipids which
possess the characteristics of lipids. Include glycerol
and other alcohols, fatty acids, fat soluble vitamins,
steroid hormones, hydrocarbons, ketone bodies.
4. MISCELLANEOUS LIPIDS: Include a large number
of compounds possessing the characterictics of lipids.
Ex: Carotenoids, Terpenes, etc.
NEUTRAL LIPIDS: Uncharged lipids. Mono, Di and
Triacylglycerols, cholesterol, cholesteryl esters.
 ROLE OF TRIGLYCERIDES
• Triacylglycerols / triglycerides are esters of glycerol with fatty
acids.
• Insoluble in water. Non – polar.
• Commonly known as neutral fats.
• Triacylglycerols – most abundant group of lipids that function as
fuel reserves of animals.
• The fat reserve of normal humans is sufficient to meet the body’s
caloric req. for 2-3 mths.
• Adipocytes of adipose tissue are specialised for storage of TAGs.
• The fat is stored in the form of globules dispersed in the entire
cytoplasm.
• Triglycerides store unused calories and provide the body with
energy.
• When there is an excess of triglycerides in the body, they
can be stored in the liver or in fat cells to supply the body
with energy when it is required.
• When TAGs are needed, the body releases them as fatty
acids, which fuel body movement, create heat and provide
energy for body processes.
• This is a natural process that provides a sustained source
of energy for the body, particularly between meals, as
triglycerides are a stored energy source.
• Triglycerides are the major form of storage lipid in
animals, and therefore normally constitute the bulk of
dietary lipid.
• TG are important contributors to fetal growth during
pregnancy.
 CHOLESTEROL
• Steroids are compounds containing a cyclic steroid ring namely CPPP
• Cyclopentanoperhydrophenanthrene.
• Steroids in the biological system include cholesterol, bile acids, Vitamin
D, sex hormones, adrenocortical hormones, etc.
• If the steroid contains one or more hydroxyl groups, it is known as
Sterol.
• In nature, sterols occur in free state .
• As esters with fatty acids.
• Cholesterol is found in association with fatty acids to form cholesteryl
esters.
• Ampiphatic in nature.
Classification:
i. Animal sterols: Ex: Cholesterol
ii. Plant sterols: Ex: Phytosterol
iii.Mycosterol: Ex: Ergosterol
• CHOLESTEROL is exclusively found in animals
and human tissues.
• Widely distributed in all cells and is a major
component of cell membranes and lipoproteins.
• Cholesterol was first isolated from bile.
• It is synthesized in the body.
• Large amounts of cholesterol is also present in
sebum secreted by the sebaceous glands.
• Human diets: ghee, butter, cheese, milk, curd, egg,
flesh foods, organ meats, fish and prawns.
• High intakes of cholesterol increases blood pressure.
 Functions of Cholesterol
• Precursor for the formation of bile acids.
• Present in cell membranes.
• Essential for maintenance of the membranes.
• Precursor for the formation of some steroid hormones such as
estrogens, androgens, progesterone.
• Essential for synthesis of adrenocortical hormones.
• Present in large amounts in the nervous tissue.
• Insulating cover for the transmission of electrical impulses in the
nervous tissue.
• Serves as precursor for the formation of dehydrocholesterol which
in turn is converted to Vit D3 in the body.
• Other biochemical functions – role in synthesis of bile acids,
hormones…
Blood of normal human being contains 150-250 mg/100ml.
 ESSENTIAL FATTY ACIDS
• The fatty acids that cannot be synthesized by the body and
should be supplied in the diet are known as Essential Fatty
Acids (EFA).
• They are PUFA – Linoleic acid (n-6)
Linolenic acid (n-3)
• Arachidonic acid becomes essential, if its precursor linoleic
acid is not provided in the diet in sufficient amounts.
• Linoleic acid → Gamma – linolenic acid → Eicosatrienoic
acid → Arachidonic acid
• Alpha linolenic acid can be converted to EPA and DHA.
• These EFA were found to be highly effective in promoting
the growth of rats fed fat-free diets.
• The metabolites of arachidonic acid often are referred to as
“eicosanoids.”
• Eicosanoids include prostaglandins, prostacyclins,
thromboxanes and leukotrienes.
• Prostaglandins are involved in the vasodilatation in pregnancy
• The prostaglandin responsible for increased vasodilatation in
normal pregnancy is prostacyclin (PGI2) because of its potent
effect to relax the smooth muscle of blood vessels and lower
systemic arterial blood pressure
• The name prostaglandin derives from the prostate gland.
• Prostaglandins were discovered to be produced by the 
seminal vesicles.
• Many other tissues secrete prostaglandins and that they
perform a variety of functions. 
• Prostacyclins are formed in arterial walls and are
powerful inhibitors of platelet aggregation.
• They relax arterial walls and promote lowering of
blood pressure.
• Thromboxanes are found in platelets.
• They stimulate platelets to aggregate.
• Important for wound healing, contract the arterial
wall and promote an increase in blood pressure.
• Archidonic acid → Leukotriene B4 – infammatory
action.
• EPA → Leukotriene B5 – less inflammatory.
 OMEGA 6
• Major fatty acid of the epidermis – arachidonic
acid
• Serves in the epidermis, regulating barrier
function
• Involved in maintaining the integrity of the
skin and fragility of mitochondrial membranes.
 Omega - 3
• EPA and DHA.
• Structural component for providing the optimal function of
cellular membranes in health or disease states.
• May generate changes in membrane fluidity, enzyme
activity,etc.
• Prevent breast and colon cancers by inhibiting tumour cell
growth.
• Anti- inflammatory effect
• Relax muscles and blood vessels of the uterus and reduce
menstrual cramps.
• Detoxification
• A diet rich in omega – 3 fatty acids contributes to a high degree
of intelligence and memory by improving concentration and
mental alertness.
 General functions of EFA
• Energy stores: as tryglycerides serving as energy stores
for sebum precursors.
• Bactericidal activity against staphylococci, streptococci,
pneumococci
• Involved in the membrane composition of T cells or B
cells.
• Role in foetal growth and early human development.
• DHA protects against retinal degeneration.
• Role in cardiovascular disease – exert reverse effects on
atherogenesis and thrombus formation.
• They have anti-inflammatory, anti – thombogenic, anti-
arrhythmic, hypolipidemic and vasodilatory properties.
 DEFICIENCY OF EFA
Can occur in fat malabsorption and occasionally in protein
calorie malnutrition where there is a deficiency of fat calories.
1) RATS: fat – free diet – normal growth upto 8 weeks.
 Growth slowed down and stopped by 2 weeks.
 Squamous dermatitis developed
 Hemorrhages on the tail.
2) INFANTS : Linoleic acid – Hansen and Colleagues (1963)
 Perianal irritation and dryness of skin within a few weeks.
 Supplementation of Linoleic acid cured the condition.
3) ADULTS AND CHILDREN: (Phrynoderma)
 Gopalan and associates.
 Cured by administration of linseed/safflowerseed oil rich in
EFA + VitB2 complex.
 Sources
• Linoleic acid: Corn, cotton seed, safflower,
soybean oils – good souces.
• Alpha – linolenic acid : fish oils, GLV, flax
seeds, soybean, rapeseed, walnuts.
• Gamma – linolenic acid : barley, oats
• n-3 fatty acids (EPA and DHA) : fish and fish
oils, cod liver oils.
 LIPOPROTEINS
• Lipoproteins are molecular complexes of lipids with proteins.
• They are the transport vehicles for lipids in the circulation.
• There are five types of lipoproteins, namely chylomicrons, very low density
lipoproteins (VLDL), Low density lipoproteins (LDL), high density lipoproteins
(HDL) and free fatty acid-albumin complexes.
• Lipoproteins are molecular complexes that consist of lipids and proteins
(conjugated proteins).
• They function as transport vehicles for lipids in blood plasma.
• Lipoproteins deliver the lipid components (cholesterol, triacylglycerol, etc.) to
various tissues for utilization.
• Structure:
• A lipoprotein basically consists of a neutral lipid core (with triacylglycerol and/or
cholesteryl ester) surrounded by coat shell of phospholipids, apoproteins and
cholesterol.
• The polar portions (amphiphilic) of phospholipids and cholesterol are exposed on
the surface of lipoproteins so that lipoprotein is soluble in aqueous solution.
 CLASSIFICATION OF LIPOPROTEINS: Five major classes
 Chylomicrons : They are synthesized in the intestine and transport
exogenous (dietary) triacylglycerol to various tissues.
• They consist of highest (99%) quantity of lipid and lowest
(1%)concentration of protein.
• The chylomicrons are the least in density and the largest in size, among
the lipoproteins.
 Very low density lipoproteins (VLDL):They are produced in liver and
intestine and are responsible for the transport of endogenously
synthesized triacylglycerols.
 Low density lipoproteins (LDL) : They are formed from VLDL in the
blood circulation.
• They transport cholesterol from liver to other tissues
 High density lipoproteins (HDL) : They are mostly synthesized in liver.
• Three different fractions of HDL (1, 2 and 3) can be identified by
ultracentrifugation.
• HDL particles transport cholesterol from peripheral tissues to liver.
Free fatty acids – albumin: FFA in the circulation
are in a bound form to albumin.
• Each molecule of albumin can hold about 20- 30
molecules of free fatty acids.
Apolipoproteins (apoproteins): The protein
components of lipoproteins are known as
apolipoproteins or, simply, apoproteins.
• Functions:
 Act as structural components of lipoproteins
 Recognize the cell membrane surface receptors.
 Activate enzymes involved in lipoprotein
metabolism.
 DEPOSITION & STORAGE OF LIPIDS
• After transport through the circulation, triglycerides are hydrolyzed
yet again to fatty acids in the adipose tissue.
• There they are transported into adipose cells, where once again they
are resynthesized into triglycerides and stored as droplets.
• Fat or adipose tissue essentially consists of cells, whereby the interior
of each cell is largely occupied by a fat droplet.
• The triglyceride in these droplets is available to the body on demand
as communicated to adipose tissue by hormone messengers.
• Lipids are stored as TAG.
• For TAGs to enter the cells, lipoprotein lipase is required to hydrolyze
them into fatty acids and glycerol again.
• The formation of TAGs requires a glycerol backbone, which can only
come from glycolysis.
• Consequently, glucose is the key signal for fat storage.
• The glycerol backbone of TAG is formed from
dihydroxyacetone phosphate, produced from the preparatory
phase of glycolysis (along with glyceraldehyde-3-
phosphate).
• Glycerol is three carbons, and therefore, each carbon can
bond together with a fatty acid.
• The bonding of the glycerol and fatty acids occurs mainly
within the cytosol of hepatocytes or adipose tissue in
ruminants (or the mammary gland in lactating animals).
• Once the TAGs have been formed, they are attached to
lipoproteins and deposited in the blood for transport.
• The lipoprotein complexes are recognized by lipoprotein
lipase, and the TAGs are removed and deposited as fat (e.g.,
fat pads in chickens, back fat in pigs).
 RANCIDITY
A. Hydrolytic rancidity: When fat is hydrolysed by lipase, free fatty
acids are formed. Partial hydrolysis of TAG by bacterial enzymes.
The odours of low molecular weight fatty acids contribute to the
rancidity.
B. Oxidative rancidity: Oxidation of USFA. The addition of oxygen to
the unsaturated linkage results in the formation of peroxide which
on decomposition yields aldehydes and ketones having off – odour.
C. Absorptive rancidity: Fats have a tendency to absorb smell, flavour.
D. Ketonic rancidity: Action of fungi- Aspergillus niger, Penicillium
on oil seeds – formation of ketonic compound – action of enzyme.
ANTI -OXIDANTS: Substances which can prevent the occurence of
oxidative rancidity.
Ex: Tocopherols, gallic acid, etc – preparation of fats and oils.
BHA, BHT - Food preservation
 FATTY ACID OXIDATION
• Fatty acids in the body – mainly oxidized by β – oxidation.
• β – oxidation is defined as the oxidation of fatty acids on the β –
carbon atom.
• Results in the sequential removal of a 2 carbon fragment – acetyl
CoA.
• Stages & tissues: 3 stages
I. Activation of fatty acids occurring in the cytosol. (2 steps)
II. Transport of fatty acids into mitochondria. (4 steps)
III. β – oxidation proper in the mitochondrial matrix. (4 reactions).
• Fatty acids are oxidized by most of the tissues in the body.
• Brain, erythrocytes, adrenal medulla – cannot utilize fatty acids
for energy req.
 METABOLISM OF LIPIDS
• Palmitoyl-CoA is a long-chain fatty acyl-CoA resulting from
the formal condensation of the carboxy group of hexadecanoic
acid with the thiol group of coenzyme A
• Palmitoyl-CoA is part of the carnitine shuttle system, which
transports other fatty acyl-CoA molecules into the 
mitochondria for β-oxidation.
• Complete oxidation of one molecule of palmitic acid yields
129 ATP molecules:
• C15H31COOH+8CoASH+ATP+7FAD+7NAD+
+7H2o→8CH3COSCoA+AMP+PPi+7FADH2+7NADH+7H
+
• Each molecule of acetyl-CoA yields 12 ATP (12 × 8 = 96);
FADH2 yields 2 ATP (7 × 2 = 14); NADH yields 3ATP (7 × 3
= 21); and two high-energy bonds are consumed (-2; ATP → 
 Energetics of β-Oxidation
• Palmitoyl-CoA yields 8 acetyl-CoA molecules and 14 pairs of 
hydrogen atoms, by seven cycles through the β-oxidation system.
• Acetyl-CoA can be oxidized in the TCA cycle, used for the synthesis of 
fatty acid or cholesterol, or used for the formation of ketone bodies in
liver. 
• β-Oxidation of an acyl-CoA with an uneven number of carbon atoms also
yields a propionyl-CoA during the acetyl-CoA acyltransferase reaction of
the last cycle.
• Two high-energy bonds are consumed in the activation of a fatty acid
molecule.
• Every mole of fatty acyl-CoA that cycles through reactions 1–4 produces
1 mol of FADH2, 1 mol of NADH, and 1 mol of acetyl-CoA.
• On the last pass of an even-chain-length fatty acid, 2 mol of acetyl-CoA
are formed.
• The final pass of an odd-chain-length molecule releases 1 mol of
propionyl-CoA.
 INHIBITOR OF CARNITINE SHUTTLE
• Carnitine acyl transferase I – inhibited by malonyl CoA (key
metabolite involved in fatty acid synthesis – cytosol).
• While fatty acid synthesis is in progress  oxidation of fatty
acids does not occur because carnitine shuttle is impaired.
• Carnitine – acylcarnitine translocase – carrier protein.
III. β – oxidation proper : Each cycle – liberates a 2 carbon unit
(acetyl CoA) – 4 reactions
 Oxidation
 Hydration
 Oxidation
 Cleavage
• The new acyl CoA (2 carbons less than the original) – reenters β
– oxidation cycle
• The process continues till the fatty acid is completely oxidized.
SUMMARY OF β – OXIDATION OF PALMITOYL CoA
• Palmitoyl CoA + 7 CoASH + 7 FAD + 7  NAD+ + 7H20
 8 acetyl CoA + 7 FADH2 + 7 NADH + 7H+
• Palmitoyl CoA undergoes 7 cycles of β – oxidation to yield
8 acetyl CoA.
• Acetyl CoA can enter citric acid cycle & get completely
oxidized to CO2 & H20.
 ENERGETICS OF β – OXIDATION
• Ultimate aim of fatty acid oxidation is to generate
energy.
• Standard free energy of palmitate = 2340 Cal
• Net yield of ATP for 1 molecule of palmitate = 129
• Energy yield by its oxidation = 129 X 7.3 Cal = 940
Cal. (since 1ATP = 7.3Cals)
• Efficiency of energy conservation by fatty acid
oxidation = 940 / 2340 X 100 = 40 %.
OXIDATION OF ODD CARBON CHAIN FATTY ACIDS
• β – oxidation of SFA containing odd number of
carbon atoms – same manner as for even carbon
fatty acids.
• Difference :
• In the final β – oxidation cycle – 3 carbon fragment
is left behind.
• Propionyl CoA  Succinyl CoA (enters TCA
cycle).
 OXIDATION OF USFA
• Due to the presence of double bonds – USFA are not reduced to the same extent
as SFA. Oxidation of USFA provides less energy than that of SFA
• Most of the reactions involved in the oxidation of USFA are the same as found
in β – oxidation of SFA
• The presence of double bonds poses problem for β – oxidation to proceed.
• This problem is overcome by 2 additional enzymes-
 Isomerase
 Epimerase.
• Degradation of fatty acids having cis-double bonds on even-numbered carbons
requires the presence of auxiliary enzymes in addition to the enzymes of the
core beta-oxidation cycle.
• Two alternative pathways have been described to degrade these fatty acids:
 One pathway involves the participation of the enzymes 2, 4-dienoyl-coenzyme
A (CoA) reductase and Delta(3)-Delta(2)-enoyl-CoA isomerase,
 Second pathway involves the epimerization of R-3-hydroxyacyl-CoA via a 3-
hydroxyacyl-CoA epimerase or the action of two stereo-specific enoyl-CoA
hydratases. 
• Unsaturated and polyunsaturated fatty acids also are degraded by β-oxidation. However,
additional reactions are required to metabolize pre-existing double bonds that would otherwise
interfere with the complete β-oxidation of unsaturated fatty acids. All double bonds found
in unsaturated fatty acids can be classified as either odd- or even-numbered double bonds. Both
classes are present in linoleic acid, which contains an odd-numbered double bond at position 9
and an even-numbered double bond at position 12.
• The degradation of linoleic acid therefore illustrates the β-oxidation of all unsaturated fatty
acids. As outlined in the figure, linoleoyl-CoA (I; all Roman numerals refer to compounds),
after passing 3 times through the β-oxidation cycle, yields 3-cis,6-cis-dodecadienoyl-CoA (II).
This metabolite cannot enter another cycle of β-oxidation due to interference by the double
bond at position 3.
• However, an additional (auxiliary) enzyme, Δ 3,Δ2-enoyl-CoA isomerase (enoyl-CoA
isomerase), converts 3-cis,6-cis-dodecadienoyl-CoA (II) to 2-trans,6-cis-dodecadienoyl-CoA
(III) that can complete its pass through one cycle of β-oxidation to yield 4-cis-decenoyl-CoA
(IV). 4-cis-Decenoyl-CoA is dehydrogenated by acyl-CoA dehydrogenase to 2-trans,4-cis-
decadienoyl-CoA (V), which is not a substrate of β-oxidation but which is reduced by
nicotanamide adenine dinucleotide phosphate (NADPH) in the presence of 2,4-dienoyl-CoA
reductase, the second auxiliary enzyme, to 3-trans-decenoyl-CoA (VI).
• The latter compound is converted by enoyl-CoA isomerase to 2-trans-decenoyl-CoA (VII) that
can be completely degraded by β-oxidation. A third auxiliary enzyme, Δ3,5,Δ2,4-dienoyl-CoA
isomerase (dienoyl-CoA isomerase), catalyzes the isomerization of 3,5-dienoyl-CoA to 2,4-
dienoyl-CoA.
• This reaction facilitates the complete β-oxidation of 3,5-dienoyl-CoAs that are minor
metabolites of unsaturated fatty acids with odd-numbered double bonds.