A lipid is chemically defined as a substance that is insoluble in water and soluble in alcohol, ether, and chloroform. Lipids are an important component of living cells. Together with carbohydrates and proteins, lipids are the main constituents of plant and animal cells. Cholesterol and triglycerides are lipids.

1. Lipids
Md. Saiful Islam
B.Pharm, M.Pharm (PCP)
North South University
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2. Lipids:
Lipids are water-insoluble organic biomolecules that can be extracted
from cells and tissues by nonpolar solvents, eg, chloroform, ether
or benzene. There are several different families or classes of
lipids but all drives their distinctive properties from the
hydrocarbon nature of a major portion of their structure.
Although lipids are a distinct class of biomolecules but they often
occur combined with other classes of biomolecules for specialized
biological functions, such as glycolipids, which contain both
carbohydrate and lipid group and lipoproteins, which contain both
lipids and proteins.

3. Classification of lipids:
Complex lipids: Backbone
Acylglycerols glycerol
phosphoglycerides glycerol 3-phosphate
Sphingolipids sphingosine
waxes Nonpolar alcohols of high molecular
weight
Lipids have several important biological functions:
a) As structural components of cell membranes
b) As storage and transport forms of metabolic fuel
c) As a protective coating on the surface of many organisms, and
d) As cell-surface components concerned in cell recognition, species
specificity and tissue immunity

4. The complex lipids which characteristically contain fatty acids as
component and differs in the backbone structures to which the
fatty acids are covalently joined. They are also called saponifiable
lipids since they yield soaps (salts of fatty acids) on alkaline
hydrolysis.
The other great group of the lipids consists of the simple lipids,
which do not contain fatty acids.
Simple lipids:
Terpenes, Steroids, Prostaglandins

5. Fatty acids:
Fatty acids are characteristic components of all the complex lipids.
Although fatty acids occur in very large amounts as building block
components of the complex lipids, only traces occur in free form in
cells and tissues. Over 100 different kinds of fatty acids have been
isolated from various lipids of animals, plants and microorganisms. All
possess a long hydrocarbon chain and a terminal carboxyl group. The
hydrocarbon chain may be saturated, as in palmitic acid, or it may have
one or more double bonds as in oleic acid. Fatty acids differ from each
other primarily in chain length and in the number and position of their
unsaturated bonds. They are often symbolized by a shorthand
notation that designates the length of the carbon chain and the
number, position and configuration of the double bonds. Thus palmitic
acid (16 carbons, saturated) is symbolized as C16:0 and oleic acid (18
carbons and one double bond between carbon 9 and 10) is symbolized
as C18:19.

6. The most abundant fatty acids have an even number of of carbon
atoms with chains between 14 and 22 carbon atoms long, but those
with 16 and 18 carbons predominate. The most common among the
saturated fatty acids are palmitic acid (C16:0) and stearic acid
(C18:0) and among the unsaturated fatty acids Oleic acid (C18:19).
Saturated fatty acids:
Symbol Structure Common name
12:0 CH3(CH2)10COOH Lauric acid
14:0 CH3(CH2)12COOH Myristic acid
16:0 CH3(CH2)14COOH Palmitic acid
18:0 CH3(CH2)16COOH Stearic acid
20:0 CH3(CH2)18COOH Arachidic acid

7. Unsaturated fatty acids predominate over the saturated ones,
particularly in higher plants and in animals living at low temperatures.
Unsaturated fatty acids have lower melting points than saturated
fatty acids of the same chain length. In most monounsaturated fatty
acids of higher organisms there is a double bond between carbon
atom 9 and 10. in most polyunsaturated fatty acids one double bond is
between 9 and 10 and the additional double bonds usually occur
between the 9,10 double bond and the methyl-terminal end of the
chain. In most types of polyunsaturated fatty acids the double bonds
are separated by one methylene group,
for example: –CH=CH-CH2-CH=CH-

8. Unsaturated Fatty acids:
Symbol Structure Common name
16:19 CH3(CH2)5CH=CH(CH2)7COOH Palmitoleic acid
18:19 CH3(CH2)7CH=CH(CH2)7COOH Oleic acid
18:29,12 CH3(CH2)4CH=CHCH2CH=CH(CH2)7COOH Linoleic acid
18:39,12,15 CH3CH2CH=CHCH2CH=CHCH2CH=CH(CH2)7COOH linolenic acid
20:45,8,11,14 CH3(CH2)4(CH=CHCH2)3CH=CH(CH2)3COOH Arachidonic acid

9. Essential Fatty acids:
Fatty acids which can not synthesized by mammals and are therefore
required in the diet for survival are called essential fatty acids.
Immature rats placed on a fat free diets grow poorly, develop a scaly skin,
lose hair and ultimately die with many pathological signs, When linoleic acid is
present in the diet, these conditions do not develop, linolenic and arachidonic
acid also prevent these symptoms. Saturated and monounsaturated fatty
acids are inactive. It has been concluded that mammals can synthesize
saturated and monounsaturated fatty acids from other precursors but are
unable to make linoleic and linolenic acids.
The most essential fatty acid in mammals is linoleic acid, which makes up 10-
20% of total fatty acids of their triacylglycerols (TG) and phosphoglycerides.
Linoleic and linolenic acids can not be synthesized by mammals but must be
obtained from plant sources in which they are very abundant, linolenic acid is a
necessary precursor in mammals for the biosynthesis of arachidonic acid,
which is not found in plants.

10. Omega-6 (ω-6) Fatty acids: These are long chain polyunsaturated fatty
acids, with the first double bond beginning at the sixth carbon atom, when
counting from the methyl end of the fatty acid molecule, example: Linoleic acid,
obtained from vegetable oil, it lowers plasma cholesterol when substituted for
saturated fats. Nuts, olives, soybeans and corn oils are common sources of
these fatty acids.
Omega-3 (ω-3) Fatty acids: These are long chain polyunsaturated fatty
acids, with the first double bond beginning at the third carbon atom when
counting from the methyl end of the fatty acid molecule, example: -linolenic
acid. ω-3 fatty acids supress cardiac disease, reduce serum TG, decrease the
tendency for thrombosis, lower blood pressure and substantially reduce the
risk of cardiovascular mortality. ω-3 polyunsaturated fatty acids are found in
plants (-linolenic acid) and in fish oil (docosahexanoic acid, eicosapentanoic
acid).
Essential fatty acids are necessary precursors in the biosynthesis of a group
of fatty acid derivatives called prostaglandins, a hormone like compounds
which in trace amounts have profound effects on a number of important
physiological activities.

11. H
H
Trans fatty
acid
H
H
Cis fatty acid
Trans fatty acids: Trans fatty acids are chemically classified as
unsaturated fatty acids but behave more like saturated fatty acids
in the body ie, they elevate serum LDL and increase the risk of
coronary heart disease. Trans fatty acids do not occur naturally in
plants but occur small amounts in animals. Trans fatty acids are
formed during the hydrogenation of vegetable oils in the
manufacture of margarine. Cookies, cakes and most deep-fried
foods also contains trans fatty acids.

12. Complex fatty acids:
Acylglycerols or glycerides:
Fatty acid esters of the alcohol glycerol called acylglycerols or glycerides,
they are sometimes referred to as neutral fats.
When all the three hydroxyl group of the glycerol are esterified with fatty
acids, the structure is called triacylglycerol or triglycerids (TG). Triglycerols
are the most abundant family of lipids and the major components of storage
lipids in plant and animal cells.
Triacyglycerols that are solid at room temperature (25°C) are often referred
to as fats, and those which are liquid as oils. Diacylglycerols and
monoacyglycerols are also found in nature but in much smaller amounts.
Triacylglycerols occur in many different types according to the identity and
position of the three fatty acid components esterified to glycerol.

13. Those with a single kind of fatty acid in all three positions, called simple
triacylglycerol. Mixed triacylglycerols contain two or more different kind of
fatty acids. Most of the natural fats are extremely complex and are mixture
of simple and mixed triacylglycerols.
CH2OH
CHOH
CH2OH
CH2 – O – C – R1
CHOH
CH2OH
O
CH2 – O – C – R1
CH– O – C – R2
CH2OH
O
O
CH2 – O – C – R1
CH– O – C – R2
CH2– O – C – R3
O
O
O
Glycerol
MonoacylGlycerol
TriacylGlycerol
DiacylGlycerol

14. The melting point of triacylglycerols depends on their fatty acid
components. In general, the melting point increases with the
number and length of the saturated fatty acid components.
Because of the free hydroxyl groups, mono and diaccylglycerols
form micelles. Mono and diacylglycerols are widely used in food
industry in the production of more homogenous and more easily
processed foods. Acylglycerols are soluble in ether, chloroform,
benzene and in hot ethanol. Their specific gravity is lower than
water. Acylglycerols undergo hydrolysis when boiled with acids or
bases or by the action of lipases, eg those present in pancreatic
juice. Hydrolysis with alkali called saponification, yields a mixture
of soaps and glycerols.

15. Phosphoglycerides:
Phosphoglycerides are the second large class of complex
lipids, also called glycerol phosphatides or phospholipids or
phosphatides. They are the major components of cell
membrane and only very small amount of this class of lipids
found in elsewhere in the cell.
In phosphoglycerides, one of the primary hydroxyl group of
glycerol is esterified to phosphoric acid and the other
hydroxyl groups are esterified to fatty acids. Because
phosphoglycerides possess a polar head in addition to their
nonpolar hydrocarbon tails, they are called polar lipids.

16. The most important phosphoglycerides in higher plants and
animals are phosphatidylethanolamine and phosphatidylcholine
which contain as head groups the amino alcohols ethanolamine
and choline respectively.
Pure phosphoglycerides are white waxy solids, on exposure to air
they darken and undergo complex chemical changes because of
the tendency of their polyunsaturated fatty acid components to
be peroxidized by atmospheric oxygen. Phosphoglycerides are
soluble in most nonpolar solvents containing some water and are
extracted from cells and tissues with chloroform methanol
mixtures.

17. Sphingolipids:
This type of complex lipids contain
sphingosine or related base as their
backbone. Sphingolipids are important
membrane components in both animal and
plant cells. They are present in specially
large amounts in brain and nerve tissue.
All sphingolipids contain three
characteristic components, one molecule
of fatty acid, one molecule of sphingosine
or one of its derivatives and a polar head
group, which in some sphingolipids are
very large and complex.
CH2OH
HC-NH2
HC-OH
HC
CH
(CH2)12
CH3
Sphingosine

18. Waxes: Waxes are water insoluble solid esters of higher
fatty acids with long chain monohydroxylic fatty alcohols or
with sterols. They are soft when warm but hard when cold.
Waxes are found as protective coatings on skin, fur and
feathers, on leaves and fruits of higher plants, and on the
exoskeleton of many insects. The major components of bees
waxes are palmitic acid esters of long chain fatty alcohols
with 26 to 34 carbon atoms.

19. Simple lipids:
Terpenes: Terpenes are constructed of multiple units of the five
carbon containing hydrocarbon isoprene (2-methyl-1,3-butadiene).
Terpenes containing two isoprene units called monoterpenes, those
containing three isoprene units called sesquiterpenes, and those
containing four, six or eight isoprene units are called diterpenes,
triterpenes and tetraterpenes respectively.
Of the very large number of terpenes identified
in plants, many have characterisrtic odors or
flavors. The diterpene phytol is a component of
the photosynthetic pigment chlorophyll, the
triterpene squalene is an important precursor
for Cholesterol biosynthesis.
C – CH3
CH2
CH
CH2
Isoprene

20. Other higher terpenes include the carotenoids, a class of
tetraterpene hydrocarbons, an important carotenoid is beta
carotene, the hydrocarbon precursor of vitamin A, Natural rubber
and gutta-percha are polyterpenes, they consist of long
hydrocarbon chains containing hundreds of isoprene units in regular
linear order.
Among the most important terpenes are the three members of the
fat soluble vitamins, namely vitamin A, E and K. Another important
compound of isoprene is the ubiquinone or Cenzyme Q which
function as electron carrier in electron transport chain of
mitochondria.

21. Steroids:
Steroids are derivatives of the saturated tetracylic hydrocarbon
perhydrocyclopentanophenanthrene. There are many different
steroids, each with a distinctive function or activity, have been
isolated from natural sources. Steroids differ in the number and
position of double bonds, in the type, location, and number of
substituent functional groups. All steroids originate from the linear
triterpene squalene. Cholesterol is the most abundant in animal
tissues. Cholesterol occurs rarely in higher plants, which contain
other type of sterols known collectively as phytosterols. An
important phytosterol is ergosterol which is converted to vitamin D
on irradiation by sunlight.

22. Prostaglandins:
Prostaglandins are a family of fatty acid derivatives which have a variety of
potent biological activities of a hormonal or regulatory nature. In very small
amounts this material was found to lower blood pressure and to stimulate
certain smooth muscles to contract.
All the natural prostaglandins are biologically derived by cyclization of 20
carbon unsaturated fatty acids, such as arachidonic acid, which is formed
from the essential fatty acid linoleic acid. Five of the carbon atoms (carbon 8
through 12) are looped to form a five-membered ring. The prostaglandins are
named according to their ring substituents and the number of additional side
chain double bonds. The best known are prostaglandins E1, F1 and F2.
These in turn are the parent compound of further biologically active
prostaglandins.
The prostaglandins differ from each other with respect to their biological
activity, although all show at least some activity in lowering blood pressure
and including smooth muscle to contract, some like PGE1, antagonize the
action of certain hormones, and PGE2 may find clinical use in labor and
bringing about therapeutic abortion.

24. Physiological effect:
Inflammation: Prostaglandins appear to be one of the natural mediators of
inflammation, inflammatory reactions most often involve the joints, skin, and
eyes, and inflammation of these sites is frequently treated with corticosteroids
that inhibit prostaglandin biosynthesis. Administration of the prostaglandins
PGE2 and PGE1 induce the signs of inflammation that include redness and heat,
swelling and edema.
Pain and fever: Pyrogen activates the prostaglandin biosynthetic pathway,
resulting in the release of PGE2 in the region of hypothelamus where body
temperature is regulated.
Gastric secretion and peptic ulcer: Synthetic prostaglandins have proven to be
very effective in inhibiting gastric acid secretion in patients with peptic ulcers.
Regulation of blood pressure: Prostaglandins play an important role in
controlling blood vessel tone and arterial pressure. PGE, PGA and PGI2 lower
systemic arterial pressure, thereby increasing local blood flow.
Platelet aggregation and thrombosis: Certain prostaglandins, especially PGI2,
inhibit platelet aggregation, whereas PGE2 and TXA2 promote this clotting
process.

25. Lipoproteins:
Certain lipids associates with specific proteins to form lipoprotein
system. The lipids and proteins are not covalently joined but are
held together largely by hydrophobic interactions between the
nonpolar portions of the lipid and protein components.
The plasma lipoproteins are complexes in which the lipids and
proteins occur in a relatively fixed ratio. They carry water-
insoluble lipids between various organs via the blood. Human plasma
lipoproteins occur in four major classes that differ in density as
well as particle size. Plasma lipoproteins contain varying
proportions of proteins and different types of lipid.

26. Chylomicrons VLDL LDL HDL
Density, g/ml <0.94 0.94-1.006 1.006-1.063 1.063-1.21
Particle size, nm 75-1000 30-50 20-22 7.5-10
Protein, %dry wt 1-2 10 25 45-55
TG, % dry wt 40-95 55-65 10 3
Phospholipids, % 3-6 15-20 22 30
Cholesterol, % 3-7 15 45 18

27. Oxidation of fatty acids:
Sources of fatty acids: Mammalian tissues normally contain only
small amount of free fatty acids. By the action of hormonally
controlled lipases free fatty acids are formed from triacylglycerols
in fat or adipose tissue. The free fatty acids are then released from
the tissue, become tightly bound to serum albumin, and in this form
are carried via the blood to other tissues for oxidation. Fatty acids
delivered in this manner are first enzymatically activated in the
cytoplasm and then enter into the mitochondria for oxidation.
Long chain fatty acids are oxidized to CO2 and water in nearly all
tissues of vertebrates except the brain. However, in certain
conditions the brain can oxidize -hydroxybutyrate, an intermediate
of fatty acid catabolism. Some tissues, such as heart muscle, obtain
most of their energy from the oxidation of fatty acids.

28. Step 1: Activation and entry of fatty acids into mitochondria:
There are three stages in the entry of fatty acids into mitochondria from the
cytoplasm: a) activation of the fatty acids, esterification of the free fatty
acids with extramitochondrial CoA to yield fatty acyl-CoA; b) the transfer of
the acyl group from the fatty acyl-CoA to the carrier molecule carnitine,
followed by the transport of the acyl carnitine across the inner membrane, and
c) the transfer of the acyl group from fatty acyl carnitine to
intramitochondrial-CoA, which occurs on the inner surface of the inner
membrane.
Step 1a: activation of the fatty acids
RCOOH + ATP + CoA-SH
Acyl-CoA
synthetases
RCO – S – CoA + AMP + PPi
Fatty acyl-CoA
Fatty acid
PPi + H2O 2Pi

29. Step 1b: Transfer to carnitine: Long chain saturated fatty acids
have only a limited ability to cross the inner mitochondrial membrane
as CoA esters, but their entry is greatly stimulated by carnitine.
R – C – S –CoA +
O
H3C – N – CH2 – CH – CH2 -COOH
CH3
CH3
OH
+
Acyl-CoA Carnitine
H3C – N – CH2 – CH – CH2 -COOH
CH3
CH3
O
+
C= O
R
+ CoA - SH
Carnitine acyl transferase
Acyl-carnitine

30. Step 1c: Transfer to intramitochondrial CoA:
In the last stage of the entry process the acyl group is transferred from
carnitine to intramitochondrial CoA by the action of a second type of
carnitine acyl transferase located on the inner surface of the inner
membrane.
Acyl-carnitine + CoA Acyl-CoA + Carnitine
The intramitochondrial fatty acyl CoA now becomes the substrate of
the fatty acid oxidation system, which is situated in the inner matrix
compartment.

31. Step 2: The first Dehydrogenation step in Fatty Acid Oxidation: In this
step the fatty acyl-CoA thioester undergoes enzymatic dehydrogenation by
acyl-CoA dehydrogenase at the  and  carbon atoms to form 2- enoyl Coa
as product.
R – CH2 – CH2 – C – S – CoA + E-FAD
O
R – C = C – C – S – CoA
O
H
H23
+ E-FADH2
2- trans enoyl-CoA
Step 3: The hydration Step
The double bond of the 2- trans enoyl CoA ester is then hydrated to form 3-
hydroxy acyl CoA by the enzyme enoyl coA hydratase.
R – C = C – C – S – CoA
O
H
H
2- trans enoyl CoA
+ H2O
-H2O
R – CH2 –CH – CH2- C – S - CoA
OH
O
3 hydroxy acyl CoA

32. Step 4: The second dehydrogenation step:
In the next step of the fatty acid oxidation cycle, the 3-hydroxy
acyl CoA is dehydrogenated to form 3-keto acyl coA by 3-
hydroxyacyl CoA dehydrogenase, NAD+ is the specific electron
acceptor.
R – CH2 –C –CH2 - C – S - CoA
O O
R – CH2 –CH – CH2- C – S - CoA
OH
O
3 ketoacyl CoA

33. Step 5: The Cleavage step: In the last step of fatty acid oxidation
cycle, 3-ketoacyl CoA cleaves by interaction with a molecule of free CoA to
yield two carbon fragment acetyl CoA by the action of acetyl CoA
acetyltransferase (thiolase).
R – CH2 –C –CH2 - C – S - CoA
O O
3 ketoacyl CoA
+ CoA - SH
R – CH2 –C – S - CoA
O
CH3 - C – S - CoA
O
+
Acetyl CoA

34. The Balance Sheet for ATP production from Fatty Acids:
In one turn of fatty acid oxidation cycle, one molecule of acetyl-CoA
and two pairs of hydrogen atoms have been removed from the starting
long chain fatty acyl-CoA. If the long chain fatty acyl-CoA is palmitoyl-
CoA then after one turn of the cycle:
Palmitoyl-CoA + CoA + FAD + NAD+ + H20
Myristoyl-CoA + acetyl-CoA + FADH2 + NADH + H+
After seven turns of the cycle, one molecule of palmitoyl-CoA will
be converted to eight molecule of acetyl-CoA, 7 molecule of
NADH and 7 molecule of FADH2

35. The 8 molecule of acetyl-CoA may now enter the TCA cycle where 3 NADH,
one FADH2 and one GTP (ATP) is formed per molecule of acetyl-CoA. So,
from 8 molecule of acety-CoA, 24 NADH, 8 FADH2 and 8 GTP (ATP) is
formed. Therefore, from one molecule of Palmitoyl-CoA,
(7 + 24) = 31 NADH = 31 X 3 = 93 ATP,
(7 + 8) = 15 FADH2 = 15 X 2 = 30 ATP
8 GTP (ATP) = 8 ATP
= 131 ATP
Since two molecules of ATP is required to form palmitoyl-CoA
from palmitate, So, the net yield of ATP per molecule of palmitate
is 129.

36. Keton bodies:
In many vertebrates the liver has the enzymatic capacity to divert
some of the acetyl-CoA derived from fatty acid or pyruvate oxidation
into free acetoacetate and -hydroxy butyrate, which are transported
via the blood to the peripheral tissues, where they may be oxidized
via the TCA cycle. These copmounds together with aceton are called
keton bodies.
Acetyl-CoA + acetyl-CoA = Acetoacetyl-CoA + CoA
Acetoacetyl-CoA + H20 = Acetoacetate + CoA
Acetoacetate + NADH H+ = -hydroxy butyrate

37. After formation, keton bodies are diffuse out of the liver cells into
the blood stream and transported to the peripheral tissues. Normally
the concentration of keton bodies in the liver is rather low, but in the
fasting or in diabetic condition, it may reach very high levels. It is
known as ketosis and arises when the rate of formation of the keton
bodies by the liver exceeds the capacity of the peripheral tissues to
utilize them.
Although -hydroxy butyrate can be utilized via the TCA cycle in all
tissues, its utilization by the brain under some conditions is specially
important. Normally, the brain uses glucoses almost exclusively as its
fuel, however, in prolonged fasting, the brain may utilize -
hydroxybutyrate generated from fatty acids in the liver as its major
oxidative fuel.