Lipids

Lecture # 15
 Lipids
Lipids are unique among organic molecules because their identity is defined on the
basis of a physical property and not by the presence of a particular functional group.
Because of this, lipids come in a wide variety of structures and they have many different
functions in the cell.
Lipids differ from the other classes of naturally occurring biomolecules (carbohydrates,
proteins, and nucleic acids) in that they are more soluble in non-to-weakly polar
solvents (diethyl ether, hexane, dichloromethane) than they are in water.

The large number of carbon–carbon and carbon–hydrogen σ bonds in lipids makes

them very soluble in organic solvents and insoluble in water.

Monosaccharides (from which

carbohydrates are formed) and amino
acids (from which proteins are formed),
on the other hand, are very polar, so they
tend to be water soluble.
Lipids share many properties with
hydrocarbons.
 Classification of Lipids
Lipids can be categorized as hydrolyzable or nonhydrolyzable.
[1] Hydrolyzable lipids can be cleaved into smaller molecules by hydrolysis with water.
Most hydrolyzable lipids contain an ester linkages/unit. There are three subgroups:
waxes, triacylglycerols, and phospholipids.

[2] Nonhydrolyzable lipids cannot be cleaved into smaller units by aqueous

hydrolysis. Nonhydrolyzable lipids tend to be more varied in structure. They are of
four different types: fat-soluble vitamins, eicosanoids, terpenes, and steroids.
 Fatty Acids
• Fatty acids are carboxylic acids with long hydrocarbon chains. The fatty acids most
frequently found in nature are shown in Table 26.1.

• Because they are synthesized from acetate, a compound with two carbon atoms,
most naturally occurring fatty acids contain an even number of carbon atoms
between 12 and 20 and are generally unbranched.

• Fatty acids can be saturated with hydrogen (and therefore have no carbon–carbon
double bonds) or unsaturated (have carbon–carbon double bonds).

• Fatty acids with more than one double bond are called polyunsaturated fatty acids.
• Double bonds in naturally occurring unsaturated fatty acids are never
conjugated—they are always separated by one methylene group.
More than 100 different fatty acids are known, and about 40 occur widely.

Palmitic acid (C16) and stearic acid (C18) are the most abundant saturated fatty acids;
Oleic and linoleic acids (both C18) are the most abundant unsaturated ones.

Oleic acid is monounsaturated because it has one double bond, whereas linoleic,
linolenic, and arachidonic acids are polyunsaturated fatty acids because they have
more than one double bond.

Linoleic and linolenic acids occur in cream and are essential in the human diet; infants
grow poorly and develop skin lesions if fed a diet of nonfat milk for prolonged periods.
 Physical Properties Fatty Acids
The physical properties of a fatty acid depend on the length of the hydrocarbon chain
and the degree of unsaturation. As expected, the melting points of saturated fatty
acids increase with increasing molecular weight because of increased van der Waals
interactions between the molecules.

The double bonds in unsaturated fatty acids largely, although not entirely, have Z, or
cis geometry. This configuration produces a bend in the molecules, which prevents
them from packing together as tightly as fully saturated fatty acids. As a result,
unsaturated fatty acids have fewer intermolecular interactions and, therefore, lower
melting points than saturated fatty acids with comparable molecular weights (Table
26.1).

The melting points of the unsaturated fatty acids decrease as the number of double
bonds increases. For example, an 18-carbon fatty acid melts at 69 °C if it is saturated,
at 13 °C if it has one double bond, at -5°C if it has two double bonds, and at -11°C if it
has three double bonds.
 Waxes
Waxes are esters formed from long-chain carboxylic acids and long-chain alcohols. For
example, beeswax, the structural material of beehives, has a 26-carbon carboxylic acid
component and a 30-carbon alcohol component.

The word wax comes from the Old English weax, meaning “material of the
honeycomb.”

Carnauba wax is a particularly hard wax because of its relatively high molecular weight,
arising from a 32-carbon carboxylic acid component and a 34-carbon alcohol
component. Carnauba wax is widely used as a car wax and in floor polishes.
Waxes are common in living organisms. The
feathers of birds are coated with wax to make
them water repellent.

Some vertebrates secrete wax in order to keep

their fur lubricated and water repellent.

Insects secrete a waterproof, waxy layer on the

outside of their exoskeletons.

Wax is also found on the surfaces of certain

leaves and fruits, where it serves as a protectant
against parasites and minimizes the evaporation
of water.
 Fats and Oils:
Triacylglycerols/Triglycerides
Triacylglycerols, also called triglycerides, the most abundant lipids, are compounds in
which the three OH groups of glycerol are esterified with fatty acids.

If the three fatty acid components of a triacylglycerol are the same, the compound
is called a simple triacylglycerol.

Mixed triacylglycerols, on the other hand,

contain two or three different fatty acid
components and are more common than
simple triacylglycerols.
Not all triacylglycerol molecules from a single source are necessarily identical;
the fat or oil from a given source is likely to be a complex mixture of many
different triacylglycerols.
Substances such as lard and olive oil, for example, are mixtures of several
different triacylglycerols.
Table 16.2 lists the approximate composition of some fats and oils from
different sources.
Triacylglycerols that are solids or semisolids at room temperature are called fats.
Fats are usually obtained from animals and are composed largely of triacylglycerols
with either saturated fatty acids or fatty acids with only one double bond. The
saturated fatty acid tails pack closely together, giving the triacylglycerols relatively
high melting points, causing them to be solids at room temperature.

Liquid triacylglycerols are called oils. Oils

typically come from plant products such as
corn, soybeans, olives, and peanuts. They are
composed primarily of triacylglycerols with
unsaturated fatty acids that cannot pack tightly
together. Consequently, they have relatively low
melting points, causing them to be liquids at
room temperature.

This melting point difference correlates with the number of degrees of unsaturation
present in the fatty acid side chains. As the number of double bonds increases, the
melting point decreases, as it does for the constituent fatty acids as well.
Three-dimensional structures of a saturated and unsaturated triacylglycerol are shown in
Figure 29.2. With no double bonds, the three side chains of the saturated lipid lie parallel
to each other, making it possible for this compound to pack relatively efficiently in a
crystalline lattice, thus leading to a high melting point.
In the unsaturated lipid, however, a single Z double bond places a kink in the side chain,
making it more difficult to pack efficiently in the solid state, thus leading to a lower
melting point.
Solid fats have a relatively high percentage of saturated fatty acids. Liquid oils have a
higher percentage of unsaturated fatty acids. Table 29.3 lists the fatty acid composition
of some common fats and oils.
REACTIONS OF TRIGLYCERIDES
The hydrolysis, hydrogenation, and oxidation of
triacylglycerols
 Hydrolysis of Triacylglycerols

Hydrolysis of a triacylglycerol with water in the presence of either acid,

base, or an enzyme yields glycerol and three fatty acids. This cleavage
reaction follows the same mechanism as any other ester hydrolysis. This
reaction is the first step in triacylglycerol metabolism.
 Hydrogenation of Unsaturated fatty acids

The double bonds of an unsaturated fatty acid can be hydrogenated by using H2 at high
temperature in the presence of a transition metal (Pd, Ni etc.) catalyst.

Hydrogenation converts a liquid oil to a solid fat. This process, sometimes called
hardening, or “hardening of oils” is used to prepare margarine from vegetable oils.
Margarine and shortening are produced by hydrogenating soybean, peanut, or
cottonseed oil until the proper consistency is obtained.

Unfortunately, the hydrogenation reaction is accompanied by some cis–trans

isomerization of the double bonds that remain, producing fats with about 10% to 15%
trans unsaturated fatty acids.

Dietary intake of trans fatty acids increases cholesterol levels in the blood, thereby
increasing the risk for heart problems.

The conversion of linoleic acid into elaidic acid is an example.

Oxidation of Unsaturated Fatty acids

Allylic C– H bonds are weaker than other C– H bonds and are thus susceptible to
oxidation with molecular oxygen by a radical process.

The hydroperoxide formed by this process is unstable, and it undergoes further

oxidation to products that often have a disagreeable odor.

This oxidation process turns an oil rancid.

Polyunsaturated fats and oils are easily oxidized by
means of a radical chain reaction. In the initiation step,
a radical removes a hydrogen from a methylene group
that is flanked by two double bonds. This hydrogen is
the most easily removed one because the resulting
radical is resonance stabilized by both double bonds.
This radical reacts with O2, forming a peroxy radical with
conjugated double bonds. The peroxy radical removes a
hydrogen from a methylene group of another molecule
of fatty acid, forming an alkyl hydroperoxide. The two
propagating steps are repeated over and over.

The reaction of fatty acids with causes them to become rancid. The unpleasant taste
and smell associated with rancidity are the results of further oxidation of the alkyl
hydroperoxide to shorter chain carboxylic acids such as butyric acid that have strong
odors. The same process contributes to the odor associated with sour milk.
 Source of Energy
In the cell, the principal function of triacylglycerols is energy storage. Complete
metabolism of a triacylglycerol yields CO2 and H2O, and a great deal of energy.
This overall reaction is reminiscent of the combustion of alkanes in fossil fuels, a process
that also yields CO2 and H2O and provides energy to heat homes and power
automobiles. Fundamentally both processes convert C–C and C– H bonds to C– O bonds,
a highly exothermic reaction.
Organisms store energy in the form of triacylglycerols.

A fat provides about six times as much metabolic energy as an equal weight
of hydrated glycogen because fats are less oxidized than carbohydrates and,
since fats are nonpolar, they do not bind water. In contrast, two-thirds of the
weight of stored glycogen is water.

Animals have a subcutaneous layer of fat cells that serves as both an energy
source and an insulator.

Humans can store sufficient fat to provide for the body’s metabolic needs for
two to three months, but can store only enough carbohydrate to provide for
its metabolic needs for less than 24 hours. Carbohydrates, therefore, are used
primarily as a quick, short-term energy source, such as during strenuous
exercise.

Our long-term energy needs are met by triacylglycerols, because they store
~38 kJ/g, whereas carbohydrates and proteins store only ~16 kJ/g
 Source of Biofuels
Because triacylglycerols release heat on combustion, they can in principle
be used as fuels for vehicles.

In fact, coconut oil was used as a fuel during both World War I and World
War II, when gasoline and diesel supplies ran short.

Since coconut oil is more viscous than petroleum products and freezes at
24°C, engines must be modified to use it and it can’t be used in cold
climates.

Nonetheless, a limited number of trucks and boats can now use vegetable
oils, sometimes blended with diesel, as a fuel source.

When the price of crude oil is high, the use of these biofuels becomes
economically attractive.
 Soap
Soap has been known since at least 600 BC, when the Phoenicians prepared a curdy
material by boiling goat fat with extracts of wood ash.

The cleansing properties of soap weren’t generally recognized, however, and the use of
soap didn’t become widespread until the 18th century.

Chemically, soap is a mixture of the sodium or potassium salts of long-chain fatty acids
produced by hydrolysis (saponification) of animal fat with alkali.
Crude soap curds contain glycerol and excess alkali as well as soap but can be purified
by boiling with water and adding NaCl or KCl to precipitate the pure carboxylate salts.

The smooth soap that precipitates is dried, perfumed, and pressed into bars for
household use.

Dyes are added to make colored soaps, antiseptics are added for medicated soaps,
pumice is added for scouring soaps, and air is blown in for soaps that float.

Soaps act as cleansers because the two ends of a soap molecule are so different. The
carboxylate end of the long-chain molecule is ionic and therefore hydrophilic, or
attracted to water. The long hydrocarbon portion of the molecule, however, is nonpolar
and hydrophobic, or water avoiding, and therefore more soluble in oils.

The net effect of these two opposing tendencies is that soaps are attracted to both oils
and water.
When soaps are dispersed in water, the long hydrocarbon tails cluster together on the
inside of tangled, hydrophobic balls, while the ionic heads on the surface of the
clusters stick out into the water layer.

These spherical clusters, called micelles, are shown schematically in Figure. Grease
and oil droplets are solubilized in water when they are coated by the nonpolar,
hydrophobic tails of soap molecules in the center of micelles.
Once solubilized, the grease and dirt can be rinsed away.

A soap micelle solubilizing a grease

particle in water. An electrostatic
potential map of a fatty-acid carboxylate
shows how the negative charge is located
in the head group.
As useful as they are, soaps also have some drawbacks. In hard water, which contains
metal ions such as Mg2+, Ca2+, and Fe3+, soluble sodium carboxylates are converted into
insoluble metal salts, leaving the familiar ring of scum around bathtubs and the gray
tinge on white clothes.

Chemists have circumvented these problems by synthesizing a class of synthetic

detergents based on salts of long-chain alkylbenzenesulfonic acids.

The principle of synthetic detergents is the same as that of soaps: the alkylbenzene end
of the molecule is attracted to grease, while the anionic sulfonate end is attracted to
water.

Unlike soaps, though, sulfonate detergents don’t form insoluble metal salts in hard
water and don’t leave an unpleasant scum.
 Phospholipids
Just as waxes, fats, and oils are esters of carboxylic acids, phospholipids are esters of
phosphoric acid, H3PO4.Phospholipids are hydrolyzable lipids that contain a phosphorus
atom.

Phosphoacylglycerols (or phosphoglycerides) are the second most abundant type of lipid. They form
the principal lipid component of most cell membranes. Their structure resembles the triacylglycerols
with one important difference. In phosphoacylglycerols, only two of the hydroxy groups of glycerol
are esterified with fatty acids. The third OH group is part of a phosphodiester. Because
phosphoacylglycerols are lipids that contain a phosphate group, they are classified as phospholipids.

Phospholipids are of two general kinds:

 Glycerophospholipids
 Sphingomyelins
 Glycerophospholipids
Glycerophospholipids are based on phosphatidic acid, which contains a glycerol backbone
linked by ester bonds to two fatty acids and one phosphoric acid.

Although the fatty-acid residues can be any of the C12–C20 units typically present in fats,
the acyl group at C1 is usually saturated and the one at C2 is usually unsaturated.

The phosphate group at C3 is also bonded to an amino alcohol such as choline

ethanolamine or serine.

Phosphatidylethanolamines are also called cephalins, and phosphatidylcholines are called

lecithins. Used as emulsifying agents, lecithins are added to foods such as mayonnaise to
prevent the aqueous and fat components from separating.
The phosphorus side chain of a phosphoacylglycerol makes it different from a
triacylglycerol. The two fatty acid side chains form two nonpolar “tails” that lie
parallel to each other, while the phosphodiester end of the molecule is a charged or
polar “head.”
 Sphingolipids
Sphingolipids are also found in membranes. They are the major lipid components in the
myelin sheaths of nerve fibers. Sphingolipids contain sphingosine instead of glycerol. In
sphingolipids, the amino group of sphingosine is bonded to the acyl group of a fatty acid.

Two of the most common kinds of sphingolipids are sphingomyelins and cerebrosides. In
sphingomyelins, the primary OH group of sphingosine is bonded to phosphocholine or
phosphoethanolamine, similar to the bonding in lecithins and cephalins.

In cerebrosides, the primary OH group of sphingosine is bonded to a sugar residue through

a β-glycosidic linkage.

Sphingomyelins are phospholipids because they contain a phosphate group. Cerebrosides,

on the other hand, are not phospholipids.
 Sphingomyelins
• Sphingomyelins, the second major class of phospholipids, are derivatives of the
amino alcohol sphingosine, in much the same way that triacylglycerols and
phosphoacylglycerols are derivatives of glycerol. Other notable features of a
sphingomyelin include:
 A phosphodiester at C1.
 An amide formed with a fatty acid at C2.

Like phosphoacylglycerols, sphingomyelins are also a component of the lipid bilayer of cell
membranes. The coating that surrounds and insulates nerve cells, the myelin sheath, is
particularly rich in sphingomyelins, and is vital for proper nerve function. Deterioration of
the myelin sheath as seen in multiple sclerosis leads to disabling neurological problems.
Comparison of the structural features of the most common hydrolyzable lipids: a
triacylglycerol, a phosphoacylglycerol, and a sphingomyelin
 Membranes
Phospholipids are found widely in both plant and animal tissues and make up
approximately 50% to 60% of cell membranes. Because they are like soaps in
having a long, nonpolar hydrocarbon tail bound to a polar ionic head,
phospholipids in the cell membrane organize into a lipid bilayer.
As shown in Figure, the nonpolar tails aggregate in the center of the bilayer in
much the same way that soap tails aggregate in the center of a micelle. This bilayer
serves as an effective barrier to the passage of water, ions, and other components
into and out of cells.
 Fat-Soluble Vitamins
• Vitamins are organic compounds required in small quantities for normal
metabolism. Because our cells cannot synthesize these compounds, they must
be obtained in the diet.

• Vitamins can be categorized as fat soluble or water soluble. The fat-soluble

vitamins are lipids.

• The four fat-soluble vitamins—A, D, E, and K—are found in fruits and

vegetables, fish, liver, and dairy products.
• Although fat-soluble vitamins must be obtained from the diet, they do not
have to be ingested every day. Excess vitamins are stored in fat cells, and then
used when needed.

• Figure 29.5 shows the structure of these vitamins and summarizes their
functions.
 Eicosanoids
• The eicosanoids are a group of biologically active compounds containing
20 carbon atoms derived from arachidonic acid. The prostaglandins and
the leukotrienes are two types of eicosanoids. Two others are the
thromboxanes and prostacyclins.
All eicosanoids are very potent compounds present in low concentration in cells.
They are local mediators, meaning that they perform their function in the
environment in which they are synthesized.
This distinguishes them from hormones, which are first synthesized and then
transported in the bloodstream to their site of action.
Eicosanoids are not stored in cells; rather, they are synthesized from arachidonic
acid in response to an external stimulus.
Each eicosanoid is associated with specific types of biological activity (Table 29.4).
In some cases, the effects oppose one another. For example, thromboxanes are
vasoconstrictors that trigger blood platelet aggregation, whereas prostacyclins are
vasodilators that inhibit platelet aggregation. The levels of these two eicosanoids
must be in the right balance for cells to function properly.
 Terpenes
• Terpenes are lipids composed of repeating five-carbon units called
isoprene units. An isoprene unit has five carbons: four in a row, with a
one-carbon branch on a middle carbon.

Terpenes have a wide variety of structures. They can be acyclic or have one or
more rings. They may have only carbon and hydrogen atoms, or they may have
heteroatoms as well. The most common heteroatom in terpenes is oxygen. Many
essential oils, a group of compounds isolated from plant sources by distillation, are
terpenes. Examples include myrcene and menthol.
 Myrcene and menthol, for example, each have 10 carbon atoms,
so they are composed of two isoprene units.

Terpenes are classified by the number of isoprene units they

contain. A monoterpene contains 10 carbons and has two
isoprene units, a sesquiterpene contains 15 carbons and has
three isoprene units, and so forth. The different terpene classes
are summarized in Table 29.5.
Examples of some common Terpenes
 Steroids
• The steroids are a group of tetracyclic lipids, many of which are biologically
active.
Steroid Structure
• Steroids are composed of three six-membered rings and one five-
membered ring, joined together as drawn.
• Many steroids also contain two methyl groups, called angular methyl
groups, at the two ring junctions indicated.
• The steroid rings are lettered A, B, C, and D, and the 17 ring carbons are
numbered as shown in the Figure.
• The two angular methyl groups are numbered C18 and C19.
 Cholesterol
• Cholesterol, has the tetracyclic carbon skeleton characteristic of steroids. It
also has eight stereogenic carbons (seven on rings and one on a side chain),
so there are 28 = 256 possible stereoisomers. In nature, however, only the
following stereoisomer exists:

Cholesterol is essential to life because it forms an important component of cell

membranes and is the starting material for the synthesis of all other steroids. Humans
do not have to ingest cholesterol, because it is synthesized in the liver and then
transported to other tissues through the bloodstream. Because cholesterol has only one
polar OH group and many nonpolar C–C and C– H bonds, it is insoluble in water (and,
thus, in the aqueous medium of the blood).
 Other Steroids
In humans, most steroids function as hormones, chemical messengers that
are secreted by endocrine glands and carried through the bloodstream to
target tissues.

There are two main classes of steroid hormones: the sex hormones, which
control maturation, tissue growth, and reproduction, and the
adrenocortical hormones, which regulate a variety of metabolic processes.
 Adrenocortical Hormones
• Adrenocortical steroids are secreted by the adrenal glands, small organs
located near the upper end of each kidney.
• There are two types of adrenocortical steroids, called mineralocorticoids and
glucocorticoids.
• Mineralocorticoids, such as aldosterone, control tissue swelling by regulating
cellular salt balance between Na and K.
• Glucocorticoids, such as hydrocortisone, are involved in the regulation of
glucose metabolism and in the control of inflammation. Glucocorticoid
ointments are widely used to bring down the swelling from exposure to poison
oak or poison ivy.
 Synthetic Steroids
In addition to the many hundreds of steroids isolated from plants and animals,
thousands more have been synthesized in pharmaceutical laboratories in a search for
new drugs.
The potent physiological effects of steroids led scientists, in their search for new drugs,
to synthesize steroids that are not available in nature and to investigate their
physiological effects. Stanozolol and Dianabol are drugs developed in this way. They
have the same muscle-building effect as testosterone.
Steroids that aid in the development of muscle are called anabolic steroids. These
drugs are available by prescription and are used to treat people suffering from traumas
accompanied by muscle deterioration. The same drugs have been administered to
athletes and racehorses to increase their muscle mass.
Stanozolol was the drug detected in several athletes in the 1988 Olympics. Anabolic
steroids, when taken in relatively high dosages, have been found to cause liver tumors,
personality disorders, and testicular atrophy.