CHAPTER

Lipids

Summary
1. Lipids are the organic substances relatively insoluble in water, soluble in
organic solvents (alcohol, ether), actually or potentially related to fatty acids
and are utilized by the body.
2. Lipids are classified into simple (fats and oils), complex (phospholipids,
glycolipids), derived (fatty acids, steriod hormones) and miscellaneous
(carotenoids).
3. Fatty acids are the major constituents of various lipids. Saturated and
unsaturated fatty acids almost equally occur in natural lipids. The
polyunsaturated fatty acids (PUFA) namely linoleic acid and linolenic acid
are the essential fatty acids that need to be supplied in the diet.
4. Triacylglycerols (simply fats) are the esters of glycerol with fatty acids. They
are found in adipose tissue and primarily function as fuel reserve of animals.
Several tests (iodine number, RM number) are employed in the laboratory to
test the purity of fats and oils.
5. Phospholipids are complex lipids containing phosphoric acid.
Glycerophospholipids contain glycerol as the alcohol and these include
lecithin, cephalin, phosphatidylinositol, plasmalogen and cardiolipin.
6. Sphingophospholipids (sphingomyelins) contain sphingosine as the alcohol in
place of glycerol (in glycerophospholipids). Phospholipids are the major
constituents of plasma membranes.
7. Cerebrosides are the simplest form of glycolipids which occur in the
membranes of nervous tissue. Gangliosides are predominantly found in the
ganglions. They contain one or more molecules of N-acetylneuraminic acid
(NANA).
8. Steroids contain the ring cyclopentanoperhydrophenanthrene. The steroids of
 biological importance include cholesterol, bile acids, vitamin D, sex
hormones and cortical hormones. A steroid containing one or more hydroxyl
groups is known as sterol.
9. Cholesterol is the most abundant animal sterol. It contains one hydroxyl group
(at C3), a double bond (C5–C6) and an eight carbon side chain attached to C17.
Cholesterol is a constituent of membrane structure and is involved in the
synthesis of bile acids, hormones (sex and cortical) and vitamin D.
10. The lipids that possess both hydrophobic (non -polar) and hydrophilic (polar)
groups are known as amphipathic. These include fatty acids, phospholipids,
sphingolipids and bile salts. Amphipathic lipids are important constituents in
the bilayers of the biological membranes.

The fat speaks:

“With water, I say, ‘Touch me not’;

To the tongue, I am tasteful;

Within limits, I am dutiful;

In excess, I am dangerous!;

Lipids (Greek: lipos–fat) are of great importance to the body as the chief
concentrated storage form of energy, besides their role in cellular structure and
various other biochemical functions. As such, lipids are a heterogeneous group
of compounds and, therefore, it is difficult to define them precisely.
Lipids may be regarded as organic substances relatively insoluble in water,
soluble in organic solvents (alcohol, ether etc.), actually or potentially related
to fatty acids and utilized by the living cells.
Unlike the polysaccharides, proteins and nucleic acids, lipids are not
polymers. Further, lipids are mostly small molecules.

Classification of lipids
Lipids are broadly classified (modified from Bloor) into simple, complex,
derived and miscellaneous lipids, which are further subdivided into different
groups
1. Simple lipids : Esters of fatty acids with alcohols. These are mainly of two
types
(a) Fats and oils (triacylglycerols) : These are esters of fatty acids with
glycerol. The difference between fat and oil is only physical. Thus, oil
is a liquid while fat is a solid at room temperature.
(b) Waxes : Esters of fatty acids (usually long chain) with alcohols other
than glycerol. These alcohols may be aliphatic or alicyclic. Cetyl
alcohol is most commonly found in waxes. Waxes are used in the
preparation of candles, lubricants, cosmotics, ointments, polishes etc.
2. Complex (or compound) lipids : These are esters of fatty acids with alcohols
containing additional groups such as phosphate, nitrogenous base,
carbohydrate, protein etc. They are further divided as follows
(a) Phospholipids : They contain phosphoric acid and frequently a
nitrogenous base. This is in addition to alcohol and fatty acids.
(i) Glycerophospholipids : These phospholipids contain glycerol as
the alcohol e.g., lecithin, cephalin.
(ii) (ii) Sphingophospholipids : Sphingosine is the alcohol in this
group of phospholipids e.g., sphingomyelin.
(b) Glycolipids : These lipids contain a fatty acid, carbohydrate and
nitrogenous base. The alcohol is sphingosine, hence they are also
called as glycosphingolipids. Glycerol and phosphate are absent e.g.,
cerebrosides, gangliosides.
(c) Lipoproteins : Macromolecular complexes of lipids with proteins.
(d) Other complex lipids : Sulfolipids, aminolipids and lipopolysaccharides
are among the other complex lipids.
3. Derived lipids : These are the derivatives obtained on the hydrolysis of group
1 and group 2 lipids which possess the characteristics of lipids. These include
glycerol and other alcohols, fatty acids, mono-and diacylglycerols, lipid (fat)
 soluble vitamins, steroid hormones, hydrocarbons and ketone bodies.
4. Miscellaneous lipids : These include a large number of compounds
possessing the characteristics of lipids e.g., carotenoids, squalene,
hydrocarbons such as pentacosane (in bees wax), terpenes etc.

Neutral lipids
The lipids which are uncharged are referred to as neutral lipids. These are mono-
, di-, and triacylglycerols, cholesterol and cholesteryl esters.

Functions of lipids
Lipids perform several important functions
1. They are the concentrated fuel reserve of the body (triacylglycerols).
2. Lipids are the constituents of membrane structure and regulate the membrane
permeability (phospholipids and cholesterol).
3. They serve as a source of fat soluble vitamins (A, D, E and K).
4. Lipids are important as cellular metabolic regulators (steroid hormones and
prostaglandins).
5. Lipids protect the internal organs, serve as insulating materials and give shape
and smooth appearance to the body.

Fatty acids
Fatty acids are carboxylic acids with hydrocarbon side chain. They are the
simplest form of lipids.

Occurrence
Fatty acids mainly occur in the esterified form as major constituents of various
lipids. They are also present as free (unesterified) fatty acids. Fatty acids of
animal orgin are much simpler in structure in contrast to those of plant origin
which often contain groups such as epoxy, keto, hydroxy and cyclopentane
rings.

Even and odd carbon fatty acids

Most of the fatty acids that occur in natural lipids are of even carbons (usually
14C – 20C). This is due to the fact that biosynthesis of fatty acids mainly occurs
with the sequential addition of 2 carbon units. Palmitic acid (16C) and stearic
acid (18C) are the most common. Among the odd chain fatty acids, propionic
acid (3C) and valeric acid (5C) are well known.

Saturated and unsaturated fatty acids

Saturated fatty acids do not contain double bonds, while unsaturated fatty acids
contain one or more double bonds. Both saturated and unsaturated fatty acids
almost equally occur in the natural lipids. Fatty acids with one double bond are
monounsaturated, and those with 2 or more double bonds are collectively known
as polyunsaturated fatty acids (PUFA).

Nomenclature of fatty acids

The naming of a fatty acid (systematic name) is based on the hydrocarbon from
which it is derived. The saturated fatty acids end with a suffix -anoic (e.g.,
octanoic acid) while the unsaturated fatty acids end with a suffix -enoic (e.g.,
octadecanoic acid). In addition to systematic names, fatty acids have common
names which are more widely used (Table 3.1).

Table 3.1
Selected examples of biochemically important fatty acids
*
Total number of carbon atoms, followed by the number of double bonds and the first carbon
position of the double bond(s).
**
Essential fatty acids.

Numbering of carbon atoms

It starts from the carboxyl carbon which is taken as number 1. The carbons
adjacent to this (carboxyl C) are 2, 3, 4 and so on or alternately α, β, γ and so on.
The terminal carbon containing methyl group is known omega (ω) carbon.
Starting from the methyl end, the carbon atoms in a fatty acid are numbered as
omega 1, 2, 3 etc. The numbering of carbon atoms in two different ways is given
below

Length of hydrocarbon chain of fatty acids

Depending on the length of carbon chains, fatty acids are categorized into 3
groups—short chain with less than 6 carbons; medium chain with 8 to 14
carbons and long chain with 16 to 24 carbons.

Shorthand representation of fatty acids

Instead of writing the full structures, biochemists employ shorthand notations
(by numbers) to represent fatty acids. The general rule is that the total number of
carbon atoms are written first, followed by the number of double bonds and
finally the (first carbon) position of double bonds, starting from the carboxyl
end. Thus, saturated fatty acid, palmitic acid is written as 16 : 0, oleic acid as 18
: 1; 9, arachidonic acid as 20 : 4; 5, 8, 11, 14.
There are other conventions of representing the double bonds. Δ9 indicates
that the double bond is between 9 and 10 of the fatty acid. ω9 represents the
double bond position (9 and 10) from the ωend. Naturally occurring unsaturated
fatty acids belong to ω9, ω6 and ω3 series.

ω3 series Linolenic acid (18 : 3; 9, 12, 15)

ω6 series Linoleic acid (18 : 2; 9, 12) and arachidonic acid (20 : 4; 5, 8, 11, 14)
ω9 series Oleic acid (18 : 1; 9)

The biochemically important saturated and unsaturated fatty acids are given in
the Table 3.1.

Essential fatty acids

The fatty acids that cannot be synthesized by the body and, therefore, should be
supplied in the diet are known as essential fatty acids (EFA). Chemically, they
are polyunsaturated fatty acids, namely linoleic acid (18 : 2; 9, 12) and
linolenic acid (18 : 3; 9, 12, 15). Arachidonic acid (20 : 4; 5, 8, 11, 14) becomes
essential, if its precursor linoleic acid is not provided in the diet in sufficient
amounts. The structures of EFA are given in the Table 3.1.

Biochemical basis for essentiality

Linoleic acid and linolenic acid are essential since humans lack the enzymes that
can introduce double bonds beyond carbons 9 to 10.

Functions of EFA
Essential fatty acids are required for the membrane structure and function,
transport of cholesterol, formation of lipoproteins, prevention of fatty liver etc.
(Chapter 23). They are also needed for the synthesis of another important group
of compounds, namely eicosanoids (Chapter 32).

Deficiency of EFA
The deficiency of EFA results in phrynoderma or toad skin, characterized by
the presence of horny eruptions on the posterior and lateral parts of limbs, on the
back and buttocks, loss of hair and poor wound healing.

Isomerism in unsaturated fatty acids

Unsaturated fatty acids exhibit geometric isomerism depending on the
orientation of the groups around the double bond axis.
If the atoms or acyl groups are present on the same side of the double bond, it
is a cis configuration. On the other hand, if the groups occur on the opposite
side, it is a trans configuration. Thus oleic acid is a cis isomer while elaidic acid
is a trans isomer, as depicted in Fig.3.1. Cis isomers are less stable than trans
isomers. Most of the naturally occurring unsaturated fatty acids exist as cis
isomers.

FIG. 3.1 Cis-trans isomerism in unsaturated fatty acids.

In the cis isomeric form, there is a molecular binding at the double bond.
Thus, oleic acid exists in an L-shape while elaidic acid is a straight chain.
Increase in the number of double bonds will cause more bends (kinks) and
arachidonic acid with 4 double bonds will have a U-shape. It is believed that cis
isomers of fatty acids with their characteristic bonds will compactly pack the
membrane structure.

Hydroxy fatty acids

Some of the fatty acids are hydroxylated. β-Hydroxybutyric acid, one of the
ketone bodies produced in metabolism, is a simple example of hydroxy fatty
acids. Cerebronic acid and recinoleic acid are long chain hydroxy fatty acids.

Cyclic fatty acids

Fatty acids with cyclic structures are rather rare e.g., chaulmoogric acid found
in chaulmoogra oil (used in leprosy treatment) contains cyclopentenyl ring.

Eicosanoids
These compounds are related to eicosapolyenoic fatty acids and include
prostaglandins, prostacyclins, leukotrienes and thromboxanes. They are
discussed together (Chapter 32).

Triacylglycerols
Triacylglycerols (formerly triglycerides) are the esters of glycerol with fatty
acids. The fats and oils that are widely distributed in both plants and animals are
chemically triacylglycerols. They are insoluble in water and nonpolar in
character and commonly known as neutral fats.

Fats as stored fuel

Triacylglycerols are the most abundant group of lipids that primarily function as
fuel reserves of animals. The fat reserve of normal humans (men 20%, women
25% by weight) is sufficient to meet the body's caloric requirements for 2–3
months.

Fats primarily occur in adipose tissue

Adipocytes of adipose tissue—predominantly found in the subcutaneous layer
and in the abdominal cavity—are specialized for storage of triacylglycerols. The
fat is stored in the form of globules dispersed in the entire cytoplasm. And
surprisingly, triacylglycerols are not the structural components of biological
membranes.

Structures of acylglycerols
Monoacylglycerols, diacylglycerols and triacylglycerols, respectively consisting
of one, two and three molecules of fatty acids esterified to a molecule of
glycerol, are known (Fig.3.2). Among these, triacylglycerols are the most
important biochemically.
 FIG. 3.2 General structures of acylglycerols (For palmitoyl R = C15H31; for
stearoyl R = C17H35; For linoleoyl R = C17H31).

Simple triacylglycerols contain the same type of fatty acid residue at all the
three carbons e.g., tristearoyl glycerol or tristearin.
Mixed triacylglycerols are more common. They contain 2 or 3 different
types of fatty acid residues. In general, fatty acid attached to C1 is saturated, that
attached to C2 is unsaturated while that on C3 can be either. Triacylglycerols are
named according to placement of acyl radical on glycerol e.g., 1,3-palmitoyl 2-
linoleoyl glycerol.
Triacylglycerols of plants, in general, have higher content of unsaturated
fatty acids compared to that of animals.

Stereospecific numbering of glycerol

The structure of glycerol gives an impression that carbons 1 and 3 are identical.
This is not true in a 3-dimensional structure. In order to represent the carbon
atoms of glycerol in an unambiguous manner, biochemists adopt a stereospecific
numbering (sn) and prefix glycerol with sn.

It should be noted that C1 and C3 are different. Cells possess enzymes that
can distinguish these two carbons. Thus glycerokinase phosphorylates sn-3 (and
not sn-1) glycerol to give sn-glycerol 3-phosphate.
Properties of triacylglycerols
A few important properties of triacylglycerols, which have biochemical
relevance, are discussed below
1. Hydrolysis : Triacylglycerols undergo stepwise enzymatic hydrolysis to
finally liberate free fatty acids and glycerol. The process of hydrolysis,
catalysed by lipases is important for digestion of fat in the gastrointestinal
tract and fat mobilization from the adipose tissues.
2. Saponification : The hydrolysis of triacylglycerols by alkali to produce
glycerol and soaps is known as saponification.

3. Rancidity : Rancidity is the term used to represent the deterioration of fats

and oils resulting in an unpleasant taste. Fats containing unsaturated fatty
acids are more susceptible to rancidity.
Rancidity occurs when fats and oils are exposed to air, moisture, light,
bacteria etc. Hydrolytic rancidity occurs due to partial hydrolysis of
triacylglycerols by bacterial enzymes. Oxidative rancidity is due to oxidation of
unsaturated fatty acids. This results in the formation of unpleasant products such
as dicarboxylic acids, aldehydes, ketones etc. Rancid fats and oils are unsuitable
for human consumption.

Antioxidants
The substances which can prevent the occurrence of oxidative rancidity are
known as antioxidants. Trace amounts of antioxidants such as tocopherols
(vitamin E), hydroquinone, gallic acid and α-naphthol are added to the
commercial preparations of fats and oils to prevent rancidity. Propyl gallate,
butylated hydroxyanisole (BHA) and butylated hydroxytoluene (BHT) are the
antioxidants used in food preservation.
4. Lipid peroxidation in vivo : In the living cells, lipids undergo oxidation to
produce peroxides and free radicals which can damage the tissue. The free
radicals are believed to cause inflammatory diseases, ageing, cancer,
atherosclerosis etc. It is fortunate that the cells possess antioxidants such as
vitamin E, urate and superoxide dismutase to prevent in vivo lipid
peroxidation (Chapter 34).

Tests to check purity of fats and oils

Adulteration of fats and oils is increasing day by day. Several tests are employed
in the laboratory to check the purity of fats and oils. Some of them are discussed
hereunder

Iodine number
It is defined as the grams (number) of iodine absorbed by 100 g of fat or oil.
Iodine number is useful to know the relative unsaturation of fats, and is directly
proportional to the content of unsaturated fatty acids. Thus lower is the iodine
number, less is the degree of unsaturation. The iodine numbers of common
oils/fats are given below.

Fat/oil Iodine number

Coconut oil 7 — 10
Butter 25 — 28
Palm oil 45 — 55
Olive oil 80 — 85
Groundnut oil 85 — 100
Cottonseed oil 100 — 110
Sunflower oil 125 — 135
Linseed oil 175 — 200

Determination of iodine number will help to know the degree of adulteration

of a given oil.

Saponification number
It is defined as the mg (number) of KOH required to hydrolyse (saponify) one
gram of fat or oil. Saponification number is a measure of the average molecular
size of the fatty acids present. The value is higher for fats containing short chain
fatty acids. The saponification numbers of a few fats and oils are given below

Human fat 195–200

Butter 230–240
Coconut oil 250–260

Reichert-Meissl (RM) number

It is defined as the number of ml 0.1 N KOH required to completely neutralize
the soluble volatile fatty acids distilled from 5 g fat. RM number is useful in
testing the purity of butter since it contains a good concentration of volatile fatty
acids (butyric acid, caproic acid and caprylic acid). This is in contrast to other
fats and oils which have a negligible amount of volatile fatty acids. Butter has a
RM number in the range 25-30, while it is less than 1 for most other edible oils.
Thus any adulteration of butter can be easily tested by this sensitive RM
number.

Acid number
It is defined as the number of mg of KOH required to completely neutralize free
fatty acids present in one gram fat or oil. In normal circumstances, refined oils
should be free from any free fatty acids. Oils, on decomposition—due to
chemical or bacterial contamination—yield free fatty acids. Therefore, oils with
increased acid number are unsafe for human consumption.

Phospholipids
These are complex or compound lipids containing phosphoric acid, in addition
to fatty acids, nitrogenous base and alcohol (Fig.3.3).

FIG. 3.3 Structures of phospholipids.

There are two classes of phospholipids

1. Glycerophospholipids (or phosphoglycerides) that contain glycerol as the
alcohol.
2. Sphingophospholipids (or sphingomyelins) that contain sphingosine as the
 alcohol.

Glycerophospholipids
Glycerophospholipids are the major lipids that occur in biological membranes.
They consist of glycerol 3-phosphate esterified at its C1 and C2 with fatty acids.
Usually, C1 contains a saturated fatty acid while C2 contains an unsaturated fatty
acid.
1. Phosphatidic acid : This is the simplest phospholipid. It does not occur in
good concentration in the tissues. Basically, phosphatidic acid is an
intermediate in the synthesis of triacylglycerols and phospholipids.
The other glycerophospholipids containing different nitrogenous bases or
other groups may be regarded as the derivatives of phosphatidic acid.
2. Lecithins (phosphatidylcholine): These are the most abundant group of
phospholipids in the cell membranes. Chemically, lecithin (Greek : lecithos—
egg yolk) is a phosphatidic acid with choline as the base.
Phosphatidylcholines represent the storage form of body's choline.

Biomedical/clinical concepts
Lipids are important to the body as constituents of membranes,
source of fat soluble (A, D, E and K) vitamins and metabolic
regulators (steroid hormones and prostaglandins).
Triacylglycerols (fats) primarily stored in the adipose tissue are
concentrated fuel reserves of the body. Fats found in the
subcutaneous tissue and around certain organs serve as thermal
insulators.
The unsaturated fatty acids–linoleic and linolenic acid—are
essential to humans, the deficiency of which causes phrynoderma
or toad skin.
The cyclic fatty acid, namely chaulmoogric acid,is employed in
the treatment of leprosy.
Fats and oils on exposure to air, moisture, bacteria etc. undergo
rancidity (deterioration). This can be prevented by the addition of
certain antioxidants (vitamin E, hydroquinone, gallic acid).
In food preservation, antioxidants—namely propyl gallate,
 butylated hydroxyanisole and butylated hydroxytoluene—are
commonly used.

(a) Dipalmitoyl lecithin is an important phosphatidylcholine found in lungs. It is

a surface active agent and prevents the adherence of inner surface of the lungs
due to surface tension. Respiratory distress syndrome in infants is a disorder
characterized by the absence of dipalmitoyl lecithin.
(b) Lysolecithin is formed by removal of the fatty acid either at C1 or C2 of
lecithin.
3. Cephalins (phosphatidylethanolamine) : Ethanolamine is the nitrogenous
base present in cephalins. Thus, lecithin and cephalin differ with regard to the
base.
4. Phosphatidylinositol : The steroisomer myo-inositol is attached to
phosphatidic acid to give phosphatidylinositol(PI). This is an important
component of cell membranes. The action of certain hormones (e.g. oxytocin,
vasopressin) is mediated through PI.
5. Phosphatidylserine : The amino acid serine is present in this group of
glycerophospholipids. Phosphatidylthreonine is also found in certain tissues.
6. Plasmalogens : When a fatty acid is attached by an ether linkage at C1 of
glycerol in the glycerophospholipids, the resultant compound is plasmalogen.
Phosphatidal-ethanolamine is the most important which is similar in structure
to phosphatidylethanolamine but for the ether linkage (in place of ester). An
unsaturated fatty acid occurs at C1. Choline, inositol and serine may substitute
ethanolamine to give other plasmalogens.
7. Cardiolipin : It is so named as it was first isolated from heart muscle.
Structurally, a cardiolipin consists of two molecules of phosphatidic acid held
by an additional glycerol through phosphate groups. It is an important
component of inner mitochondrial membrane and essential for mitrochondrial
function. Decreased cardiolipin levels may result in mitochondrial
dysfunction, aging, hypothyroidism, cardioskeletal myopathy (Barth
syndrome). Cardiolipin is the only phosphoglyceride that possesses antigenic
properties.

Sphingomyelins
Sphingosine is an amino alcohol present in sphingomyelins
(sphingophospholipids). They do not contain glycerol at all. Sphingosine is
attached by an amide linkage to a fatty acid to produce ceramide. The alcohol
group of sphingosine is bound to phosphorylcholine in sphingomyelin structure
(Fig.3.3). Sphingomyelins are important constituents of myelin and are found in
good quantity in brain and nervous tissues.
Ceramide, acts as a second messenger (signaling molecule) by regulating
programmed cell death (apoptosis), cell cycle and cell differentiation. A
ceramide containing a 30-carbon fatty acid is a major component of skin, and it
regulates skin's water permeability.

Functions of phospholipids
Phospholipids constitute an important group of compound lipids that perform a
wide variety of functions
1. In association with proteins, phospholipids form the structural components of
membranes and regulate membrane permeability.
2. Phospholipids (lecithin, cephalin and cardiolipin) in the mitochondria
maintain the conformation of electron transport chain components, and thus
cellular respiration.
3. Phospholipids participate in the absorption of fat from the intestine.
4. Phospholipids are essential for the synthesis of different lipoproteins, and thus
participate in the transport of lipids.
5. Accumulation of fat in liver (fatty liver) can be prevented by phospholipids,
hence they are regarded as lipotropic factors.
6. Arachidonic acid, an unsaturated fatty acid liberated from phospholipids,
serves as a precursor for the synthesis of eicosanoids (prostaglandins,
prostacyclins, thromboxanes etc.).
7. Phospholipids participate in the reverse cholesterol transport and thus help in
the removal of cholesterol from the body.
8. Phospholipids act as surfactants (agents lowering surface tension). For
instance, dipalmitoyl phosphatidylcholine is an important lung surfactant.
Respiratory distress syndrome in infants is associated with insufficient
production of this surfactant.
9. Cephalins, an important group of phospholipids participate in blood clotting.
10. Phosphatidylinositol is the source of second messengers—inositol
triphosphate and diacylglyceol, that are involved in the action of some
horomones.
Glycolipids
Glycolipids (glycosphingolipids) are important constituents of cell membrane
and nervous tissues (particularly the brain). Cerebrosides are the simplest form
of glycolipids. They contain a ceramide (sphingosine attached to a fatty acid)
and one or more sugars. Galactocerebroside (galactosylceramide) and
glucocerebroside are the most important glycolipids. The structure of
galactosylceramide is given in Fig.3.4. It contains the fatty acid cerebronic acid.
Sulfagalactosylceramide is the sulfatide derived from galactosylceramide.

FIG. 3.4 Structure of galactosylceramide (R = H). For

sulfagalactosylceramide R is a sulfatide .

Gangliosides
These are predominantly found in ganglions and are the most complex form of
glycosphingolipids. They are the derivatives of cerebrosides and contain one or
more molecules of N-acetylneuraminic acid (NANA), the most important sialic
acid. The structure of NANA is given in carbohydrate chemistry (Refer
Fig.2.11).
The most important gangliosides present in the brain are GM1, GM2, GD, and
GT, (G represents ganglioside while M, D and T indicate mono-, di-or tri-sialic
acid residues, and the number denotes the carbohydrate sequence attached to the
ceramide). The ganglioside, GM2 that accumulates in Tay-Sachs disease is
represented next (outline structure).
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
acidalbumin complexes. Their structure, separation, metabolism and diseases
are discussed together (Chapter 14).

Steroids
Steroids are the compounds containing a cyclic steroid nucleus (or ring) namely
cyclopentanoperhydrophenanthrene (CPPP). It consists of a phenanthrene
nucleus (rings A, B and C) to which a cyclopentane ring (D) is attached.
The structure and numbering of CPPP are shown in Fig.3.5. The steroid
nucleus represents saturated carbons, unless specifically shown as double bonds.
The methyl side chains (19 & 18) attached to carbons 10 & 13 are shown as
single bonds. At carbon 17, steroids usually contain a side chain.
 FIG. 3.5 Structures of steroids (A, B, C—Perhydrophenanthrene; D-
Cyclopentane).

There are several steroids in the biological system. These include cholesterol,
bile acids, vitamin D, sex hormones, adrenocortical hormones, sitosterols,
cardiac glycosides and alkaloids. If the steroid contains one or more hydroxyl
groups it is commonly known as sterol (means solid alcohol).

Cholesterol
Cholesterol, exclusively found in animals, is the most abundant animal sterol. It
is widely distributed in all cells and is a major component of cell membranes and
lipoproteins. Cholesterol (Greek : chole–bile) was first isolated from bile.
Cholesterol literally means ‘solid alcohol from bile.’

Structure and occurrence

The structure of cholesterol (C27H46O) is depicted in Fig.3.5. It has one hydroxyl
group at C3 and a double bond between C5 and C6. An 8 carbon aliphatic side
chain is attached to C17. Cholesterol contains a total of 5 methyl groups.
Due to the presence of an −OH group, cholesterol is weakly amphiphilic. As a
structural component of plasma membranes, cholesterol is an important
determinant of membrane permeability properties. The occurrence of cholesterol
is much higher in the membranes of sub-cellular organelles.
Cholesterol is found in association with fatty acids to form cholesteryl esters
(esterification occurs at the OH group of C3).

Properties and reactions

Cholesterol is an yellowish crystalline solid. The crystals, under the microscope,
show a notched ( ) appearance. Cholesterol is insoluble in water and soluble in
organic solvents such as chloroform, benzene, ether etc.
Several reactions given by cholesterol are useful for its qualitative
identification and quantitative estimation. These include Salkowski's test,
Liebermann-Burchard reaction and Zak's test.

Functions of cholesterol
Cholesterol is a poor conductor of heat and electricity, since it has a high
dielectric constant. It is present in abundance in nervous tissues. It appears that
cholesterol functions as an insulating cover for the transmission of electrical
impulses in the nervous tissue. Cholesterol performs several other biochemical
functions which include its role in membrane structure and function, in the
synthesis of bile acids, hormones (sex and cortical) and vitamin D (for details,
Refer Chapters 7 and 19).

Ergosterol
Ergosterol occurs in plants. It is also found as a structural constituent of
membranes in yeast and fungi. Ergosterol (Fig.3.5) is an important precursor for
vitamin D. When exposed to light, the ring B of ergosterol opens and it is
converted to ergocalciferol, a compound containing vitamin D activity.
The other sterols present in plant cells include stigmasterol and β-sitosterol.

Amphipathic lipids
As per definition, lipids are insoluble (hydrophobic) in water. This is primarily
due to the predominant presence of hydrocarbon groups. However, some of the
lipids possess polar or hydrophilic groups which tend to be soluble in water.
Molecules which contain both hydrophobic and hydrophilic groups are known as
amphipathic (Greek : amphi-both, pathos— passion).

Examples of amphipathic lipids

Among the lipids, fatty acids, phospholipids, sphingolipids, bile salts and
cholesterol (to some extent) are amphipathic in nature.
Phospholipids have a hydrophilic head (phosphate group attached to choline,
ethanolamine, inositol etc.) and a long hydrophobic tail. The general structure of
an amphipathic lipid may be represented as a polar or hydrophilic head with a
nonpolar or hydrophobic tail (Fig.3.6).

FIG. 3.6 Summary of amphipathic lipids in the formation of micelle and

lipid bilayer.

Fatty acids contain a hydrocarbon chain with a carboxyl (COO−) group at

physiological pH. The carboxyl group is polar in nature with affinity to water
(hydrophilic) while hydrocarbon chain of fatty acid is hydrophobic.

Orientation of amphipathic lipids

When the amphipathic lipids are mixed in water (aqueous phase), the polar
groups (heads) orient themselves towards aqueous phase while the nonpolar
(tails) orient towards the opposite directions. This leads to the formation of
micelles (Fig.3.6).
Micelles are primarily molecular aggregates of amphipathic lipids. Micelle
formation, facilitated by bile salts, is very important for lipid digestion and
absorption (Chapter 8).
 Biomedical/clinical concepts
The phospholipid–dipalmitoyl lecithin—prevents the adherence
of inner surface of the lungs, the absence of which is associated
with respiratory distress syndrome in infants.
Cephalins participate in blood clotting.
The action of certain hormones is mediated through
phosphatidylinositol.
Phospholipids are important for the synthesis and transport of
lipoproteins and reverse transport of cholesterol.
Cholesterol is essential for the synthesis of bile acids, hormones
(sex and cortical) and vitamin D.
Lipoproteins occur in the membrane structure, besides serving as
a means of transport vehicles for lipids.
Lipids are associated with certain disorders—obesity,
atherosclerosis, and diabetes mellitus.
Liposomes are used for administration of a variety of therapeutic
substances (drugs, proteins, nucleic acids) in order to target
specific organs or tissues.

Membrane bilayers
In case of biological membranes, a bilayer of lipids is formed orienting the polar
heads to the outer aqueous phase on either side and the nonpolar tails into the
interior (Fig.3.6). The formation of a lipid bilayer is the basis of membrane
structure.

Liposomes
They are produced when amphipathic lipids in aqueous medium are subjected to
sonification. They have intermittent aqueous phases in the lipid bilayer.
Liposomes, in combination with tissue specific antigens, are used as carriers of
drugs to target tissues.

Emulsions