LIPIDS

PHBIO 2103 UNIT 2

Catherine A. Ortega, RPh

Department of Pharmacy
University of San Carlos
Outline

• Physiologic significance of lipids

• Lipid Classifications
• Fatty acids
• Types of Lipids and their Functions
Definition

• Lipids may be broadly defined as hydrophobic or amphiphilic small molecules that

originate entirely or in part from two distinct types of biochemical subunits or
“building blocks”: ketoacyl and isoprene groups.
• Using this approach, lipids may be divided into eight categories: fatty acyls,
glycerolipids, glycerophospholipids, spingolipids, saccharolipids,
glycerophospholipids, and polyketides (derived from condensation of ketoacyl
subunits); and sterol lipids and prenol lipids (derived from condensation of isoprene
units).

*Fahy,E. et al, Journal of Lipid Research, Vol. 46, 839-862, May 2005
Physiologic Significance of Lipids

• The lipids are a heterogeneous group of compounds, including fats, oils, steroids,
waxes, and related compounds, that are related more by their physical than by their
chemical properties. They have the common property of being (1) relatively
insoluble in water and (2) soluble in nonpolar solvents such as ether and
chloroform.
• Lipids have essential roles in nutrition and health and knowledge of lipid
biochemistry is necessary for the understanding of many important biomedical
conditions, including obesity, diabetes mellitus, and atherosclerosis.
Physiologic Significance of Lipids

• They are important dietary constituents not only because of the high energy value
of fats but also because essential fatty acids and fat-soluble vitamins and other
lipophilic micronutrients are contained in the fat of natural foods.
Physiologic Significance of Lipids

• Dietary supplementation with long chain omega-3 fatty acids is believed to have
beneficial effects in a number of chronic diseases, including cardiovascular
disease, rheumatoid arthritis and dementia.
Physiologic Significance of Lipids

• Fats and oils are the most widely occurring types of lipids. Fat is stored in adipose
tissue, where it also serves as a thermal insulator in the subcutaneous tissues and
around certain organs.
• Fats also surround and insulate vital body organs, providing protection from
mechanical shock and preventing excessive loss of heat energy
• Phospholipids, glycolipids and cholesterol (a lipid) are the basic components of cell
membranes.
• Several cholesterol derivatives function as chemical messengers (hormones) within
the body
Physiologic Significance of Lipids

• Nonpolar lipids act as electrical insulators, allowing rapid propagation of

depolarization waves along myelinated nerves (the myelin sheath is rich in
sphingomyelins)
Physiologic Significance of Lipids

• Lipids are transported in the blood combined with proteins in lipoprotein particles
Physiologic Significance of Lipids

• Other lipids, although present in relatively small quantities, play crucial roles as
enzyme cofactors, electron carriers, light-absorbing pigments, hydrophobic
anchors for proteins, “chaperones” to help membrane proteins fold, emulsifying
agents in the digestive tract, hormones, and intracellular messengers.
• The lipids are an exceedingly diverse group of biologically important materials that
are distinguished by solubility
Building Blocks of Lipids
 LIPID MAPS Classification System
Categories and Examples
Category Abbreviation Example

Fatty acyls FA Dodecanoic acid

Glycerolipids GL 1-hexadecanoyl-2-(9Z-octadecenoyl)-sn-
glycerol
Glycerophospholipids GP 1-hexadecanoyl-2-(9Z-octadecenoyl)-sn-
glycero-3-phosphocholine
Sphingolipids SP N-(tetradecanoyl)-sphing-4-enine

Sterol lipids ST Cholest-5-en-3b-ol

Prenol lipids PR 2E,6E-farnesol

Saccharolipids SL UDP-3-O-(3R-hydroxy-tetradecanoyl)-aD-
N-acetylglucosamine
Polyketides PK Aflatoxin B1

E. Fahy 2010 ©
LIPID CLASSIFICATIONS
Lipid classification according to biosynthetic routes
Lipid classification: biosynthetic routes
1:condensation
1. Carbanion based Carbanion-based condensation

CATEGORIES
Fatty Acyls
Glycerolipids
Glycerophospholipids
Sphingolipids
Saccharolipids
Polyketides
 Lipid according
Lipid classification classification: biosynthetic routes
to biosynthetic routes
2: Carbocation-based condensation
2. Carbocation-based condensation
CATEGORIES
Sterol lipids
Prenol lipids
Lipid Classification according to Harper’s
Lipid Classification according to Stoker

1. Based on biochemical function of a lipid

2. Based on whether or not a lipid can be broken down into smaller units
Lipid classification based on biochemical function (Stoker)

2. Membrane lipids
1. Energy-storage (phospholipids, 3. Emulsification lipids
lipids (triacylglycerols) sphingoglycolipids, (bile acids)
and cholesterol)

4. Messenger lipids 5. Protective-coating

(steroid hormones and lipids (biological
eicosanoids) waxes)
Lipid classification based on whether a lipid can be broken down

• Classified according to whether or not saponification occurs when a lipid is placed

in basic aqueous solution
1. Saponifiable lipids – triacylglycerols, phospholipids, sphingoglycolipids and
biological waxes
2. Nonsaponifiable lipids – cholesterol, steroid hormones, bile acids and
eicosanoids)
TYPES OF FATTY ACIDS
Fatty acids

• A fatty acid is a naturally occurring monocarboxylic acid. Because of the pathway

by which they are biosynthesized, fatty acids nearly always contain an even
number of atoms and have a carbon chain that is unbranched.
• In terms of carbon chain length, fatty acids are characterized as long-chain fatty
acids (C12 to C26), medium-chain fatty acids (C8 to C10), or short-chain fatty
acids (C4 to C6).
• Fatty acids are rarely found free in nature but rather occur as part of the structure
of more complex lipid molecules
Saturated and Unsaturated Fatty Acids

• Fatty acids are classified as saturated fatty acids (SFAs), monounsaturated fatty
acids (MUFAs) or polyunsaturated fatty acids (PUFAs) based on the presence or
absence of carbon-carbon double bonds.
• A saturated fatty acid is a fatty acid with a carbon chain in which all carbon-
carbon bonds are single bonds.
Monounsaturated fatty acids

• A monounsaturated fatty acid is a fatty acid with a carbon chain in which one
carbon-carbon double bond is present.
• In biochemically important MUFAs, the configuration about the double bond is
nearly always cis.
Polyunsaturated fatty acids

• A polyunsaturated fatty acid is a fatty acid with a carbon chain in which two or
more carbon-carbon double bonds are present.
• Up to six double bonds are found in biochemically important PUFAs.
Fatty acid Nomenclature

• The most frequently used systematic nomenclature names the fatty acid after the
hydrocarbon with the same number and arrangement of carbon atoms, with -oic
being substituted for the final -e (Genevan system). Thus, saturated acids end in -
anoic, eg, octanoic acid, and unsaturated acids with double bonds end in -enoic,
eg, octadecenoic acid (oleic acid)
Double-Bond Position (Delta Nomenclature)

• Two numbers separated by a colon are used to specify the number of carbon
atoms and the number of carbon-carbon double bonds present.
• Example: 18:0
- The notation denotes a C18 fatty acid with no double bonds.

• To specify double-bond positioning within the carbon chain of an unsaturated fatty

acid, the preceding notation is expanded by adding the Greek capital letter delta
(Δ) followed by one or more superscript numbers.
• Example: 18:3 (Δ𝟗,𝟏𝟐,𝟏𝟓 )
- The notation denotes a C18 PUFA with three double bonds located between
carbons 9 and 10, 12 and 13, and 15 and 16
Omega (ω) Fatty Acid Nomenclature

• Omega-3 fatty acid – endmost double bond is three carbon atoms away from its
methyl end

• Omega-6 fatty acid – endmost double bond is six carbon atoms away from its
methyl end
EXERCISE

• Classify the fatty acid with the following structural formula

• What is the type designation?

• What is the numerical shorthand
• To which “omega” family of fatty acids does this fatty acid belong?
• What is the “delta” designation for the carbon chain double-bond locations for this
fatty acid?
EXERCISE

• Classify the fatty acid with the following structural formula

• What is the type designation?

• What is the numerical shorthand
• To which “omega” family of fatty acids does this fatty acid belong?
• What is the “delta” designation for the carbon chain double-bond locations for this
fatty acid?
Physical Properties of Fatty Acids

• Largely determined by the length and degree of unsaturation of the fatty acid
carbon chain.
• Water solubility is a direct function of carbon chain length; solubility decreases as
carbon chain length increases
• Greater surface area associated with a longer carbon chain and to the increased
opportunities that this greater surface area affords for intermolecular attractions
between fatty acid molecules
Physical Properties of Fatty Acids

• Melting point for fatty acids is strongly influenced by both carbon chain length and
degree of unsaturation; as carbon chain length increases, melting point increases.
Saturated fatty acids have higher melting points than unsaturated fatty acids with
the same number of carbon atoms. The greater the degree of unsaturation, the
greater the reduction in melting points.
• The decreasing melting point associated with increasing degree of unsaturation in
fatty acids is explained by decreased molecular attractions between carbon chains
• More double bonds = more bends = less efficient packing
Physical Properties of Fatty Acids

• For example:
• The saturated fatty acids from
12:0 to 24:0 have a waxy
consistency
• Unsaturated fatty acids of
these lengths are oily liquids.
ENERGY STORAGE LIPIDS:
TRIACYLGLYCEROLS
Triacylglycerols

• Triacylglycerols function within the body as energy-storage materials which are

concentrated primarily in adipocytes.
• Adipose tissue containing these cells is found in various parts of the body: under
the skin, in the abdominal cavity, in the mammary glands, and around various
organs.
• Triacylglycerols are much more efficient at storing energy than glycogen because
large quantities of them can be packed into a very small volume.
Triacylglycerols

• Triacylglycerol is a lipid formed by esterification of three fatty acids to a glycerol

molecule.
• A simple triacylglycerol is a triester formed from the esterification
of glycerol with three identical fatty acid molecules.
• A mixed triacylglycerol is a triester formed from the esterification of glycerol with
more than one kind of fatty acid molecule.
• Naturally occurring simple triacylglycerols are rare. Most biochemically important
triacylglycerols are mixed triacylglycerols.
Fats and Oils

• In vertebrates, specialized cells called adipocytes, or

fat cells, store large amounts of triacylglycerols as fat
droplets. Triacylglycerols are also stored as oils in
the seeds of many types of plants, providing energy
and biosynthetic precursors during seed germination.
• Adipocytes and germinating seeds contain lipases,
enzymes that catalyze the hydrolysis of stored
triacylglycerols, releasing fatty acids for export to
sites where they are required as fuel.
Triacylglycerols: Fats and Oils

• A fat is a triacylglycerol mixture that is a solid or a semi-solid at room temperature

• An oil is a triacylglycerol mixture that is a liquid at room temperature

1. Fats are composed largely of triacylglycerols in which saturated fatty acids

predominate. Such triacylglycerols can pack closely together because of the
“linearity” of their fatty acids chains.
2. Fats are generally obtained from animals, while oils typically come from plants
(although there are also fish oils)
3. Pure fats and pure oils are colorless, odorless and tasteless. The tastes, odors,
and colors associated with dietary plant oils are caused by small amounts of
other naturally occurring substances present in the plant.
Fats contain both saturated
and unsaturated fatty acids.

Oils also contain both saturated

and unsaturated fatty acids.

The difference between a fat

and an oil lies in which type of
fatty acid is more prevalent.

In fats, __________ fatty acids

are more prevalent; in oils,
_____________ fatty acids are
more prevalent.
Triacylglycerols: Fats and Oils

• In general, a higher degree of fatty acid

unsaturation is associated with oils than with
fats.
• A notable exception to this generalization is
coconut oil, which is highly saturated.
• This oil is a liquid not because it contains
many double bonds within the fatty acids but
because it is rich in shorter-chain fatty acids,
particularly lauric acid
Why is fat the preferred storage fuel?

• Oxidation of triacylglycerols yields more than twice as much energy, gram for
gram, as the oxidation of carbohydrates.
• Second, because triacylglycerols are hydrophobic and therefore unhydrated, the
organism that carries fat as fuel does not have to carry the extra weight of water of
hydration that is associated with stored polysaccharides (2 g per gram of
polysaccharide).
• Humans have fat tissue (composed primarily of adipocytes) under the skin, in the
abdominal cavity, and in the mammary glands.
Why is fat the preferred storage fuel?

• Moderately obese people with 15 to 20 kg of triacylglycerols deposited in their

adipocytes could meet their energy needs for months by drawing on their fat
stores. In contrast, the human body can store less than a day’s energy supply in the
form of glycogen.
• Carbohydrates such as glucose do offer certain advantages as quick sources of
metabolic energy, one of which is their ready solubility in water.
• In some animals, triacylglycerols stored under the skin serve not only as energy
stores but as insulation against low temperatures. Seals, walruses, penguins, and
other warm-blooded polar animals are amply padded with triacylglycerols. In
hibernating animals (bears, for example), the huge fat reserves accumulated before
hibernation serve the dual purposes of insulation and energy storage
Triacylglycerols: Good Fat vs Bad Fat

• Research studies indicate that saturated fats are “bad fat”, monounsaturated fats
are “good fat”, and polyunsaturated fats can be both “good fat” and “bad fat”
• Studies indicate that saturated fat can increase heart disease risk, that
monounsaturated fat can decrease both heart disease and breast cancer risk,
and that polyunsaturated fat can reduce heart disease risk but promote the risk of
certain types of cancers.
• Dietary fats high in “good” MUFAs include: olive, avocado, and canola oils. They
also help reduce the stickiness of blood platelets and prevent the formation of
blood clots.
• Most tree nuts and peanuts are good sources of MUFAs.
What is it about olive oil?

• A grain- and vegetable-rich diet that contains small

amounts of extra virgin olive oil (three to four
teaspoons daily) has been found to help people
with high blood pressure reduce the amount of
blood pressure medication they require, on
average, by 48%.
What is it about olive oil?

• Virgin means the oil was produced by the use of

mechanical means only, with no chemical
treatment. The term virgin oil with reference to
production method includes all grades of virgin
olive oil
Grades of Olive oil

• Extra virgin olive oil is the highest grade of virgin oil derived by cold mechanical
extraction (that the oil was not heated over a certain temperature (usually 27 °C
(80 °F)) without use of solvents or refining methods
• Virgin olive oil is a lesser grade of virgin oil, and is judged to have a good taste,
but may include some sensory defects.
• Refined olive oil is virgin oil that has been refined using charcoal and other
chemical and physical filters, methods which do not alter the glyceridic structure.
The Truth about Olive oil

• Substitution of sunflower oil for the olive oil resulted in only a 4% reduction in
medication dosage.
• The blood-pressure-reduction benefits of olive oil do not relate to the
triacylglycerols present but rather come from other compounds naturally present,
namely from antioxidant polyphenols olive oil contains.
• These antioxidants help promote the relaxation of blood vessels.
Dietary Considerations

• In general, nations whose citizens have high dietary intakes of triacylglycerols (fats
and oils) tend to have higher incidences of heart disease and certain types of
cancers.
• Contrary to the general trend, however, there are several areas of the world where
high dietary fat intake does not translate into high risks for cardiovascular disease,
obesity, and certain types of cancers.
• Relationships between dietary triacylglycerol intake and risk factors for disease
involve more than simply the total amount of triacylglycerols consumed
Triacylglycerols: Good Fat vs Bad Fat

• Inuit population (Greenland) • US Population

Both populations have diets very high in fat.

What accounts for the difference between the two peoples?
Good vs Bad Fat

• The Inuit diet is high in omega-3 fatty acids (from fish), and the U.S. diet is high in
omega-6 fatty acids (from plant oils). An American consumes about double the
amount of omega-6 fatty acids and half the amount of omega-3 fatty acids that an
Inuit consumes
• Not all fish are equal in omega-3 fatty acid content.
• Cold-water fish, also called fatty fish because of the extra amounts of fat they have
for insulation against the cold, contain more omega-3 acids than leaner, warm-
water fish.
• Fatty fish include albacore tuna, salmon, and mackerel
Essential Fatty Acids

• An essential fatty acid is a fatty acid needed in the human body that must be
obtained from dietary sources because it cannot be synthesized within the body, in
adequate amounts, from other substances.
• There are two essential fatty acids: linoleic acid and linolenic acid

Linoleic acid (18:2)

Linolenic acid (18:3)

Linoleic and Linolenic acid

• These two acids are need for proper membrane structure and as starting materials
for the production of several nutritionally important longer-chain omega-6 and
omega-3 acids.
• Linoleic acid is the starting material for the biosynthesis of arachidonic acid

• Arachidonic acid is the major starting material for eicosanoids which help regulate
blood pressure, clotting, and several other important body functions.
Linoleic and Linolenic acid

• Linolenic acid is the starting material for the biosynthesis of two additional omega-3
fatty acids

• Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are important

constituents of the communication membranes of the brain and are necessary for
normal brain development. EPA and DHA are also active in the retina of the eye.
CHEMICAL REACTIONS OF TRIACYLGLYCEROLS

HYDROLYSIS
- Under acidic conditions, the hydrolysis products are glycerol and fatty acids
- Under basic conditions, the hydrolysis products are glycerol and fatty acid salts
CHEMICAL REACTIONS OF TRIACYLGLYCEROLS

HYDROLYSIS
CHEMICAL REACTIONS OF TRIACYLGLYCEROLS

SAPONIFICATION
• Saponification is a reaction carried out in an alkaline (basic) solution. For fats and
oils, the products of saponification are glycerol and fatty acid salts.
Step 1: Hydrolysis of ester linkages to produce glycerol and three fatty acid molecules

Step 2: Reaction between fatty acid molecules and the base

CHEMICAL REACTIONS OF TRIACYLGLYCEROLS

SAPONIFICATION
• Saponification of animal fat is the process by which soap was made in pioneer
times. Soap making involved heating lard (fat) with lye.
• The cleansing action of soap is related to the structure of the carboxylate ions
present in the fatty acid salts of soap and the fact that these ions readily participate
in micelle formation.
CHEMICAL REACTIONS OF TRIACYLGLYCEROLS

HYDROGENATION
• Hydrogenation involves hydrogen addition across carbon-carbon multiple bonds,
which increases the degree of saturation as some double bonds are converted to
single bonds.

• Many food products are produced via partial hydrogenation, e.g. peanut butter is
produced from peanut oil through partial hydrogenation. Stick margarine and soft-
spread margarines are also partial hydrogenations products.
CHEMICAL REACTIONS OF TRIACYLGLYCEROLS

OXIDATION
• The carbon-carbon double bonds present in the fatty acid residues of a
triacylglycerol are subject to oxidation with oxygen from air as the oxidizing agent.
• This breaks the C-C bonds producing aldehyde and carboxylic acid products.

• This process results to rancidification of fats and oils. To avoid this, commercially
prepared foods containing fats and oils nearly always contain antioxidants.
MEMBRANE LIPIDS:
PHOSPHOLIPIDS
• Most lipid molecules in the bilayer contain at least one unsaturated fatty acid.
WHY?
Phospholipids

• Phospholipids are the most abundant type of membrane lipid.

• It is a lipid that contains one or more fatty acids, a phosphate group, a platform
molecule to which the fatty acid(s) and the phosphate group are attached, and an
alcohol that is attached to the phosphate group.
Phospholipids

• The phosphate group is the negatively-charged polar head, which is hydrophilic.

• The fatty acid chains are the uncharged, nonpolar tails which are hydrophobic.
• Since the tails are hydrophobic, they face the inside away from the water and meet
in the inner region of the membrane
• Since the heads are hydrophilic, they face outward and are attracted to the
intracellular fluid.
• If phospholipids are placed in water, they form into micelles, which are lipid
molecules that arrange themselves in a spherical form in aqueous solutions.
Glycerophospholipids vs Sphingophospholipids
Sphingophospholipids → based on a more complex C18 aminodialcohol
called sphingosine

Glycerophospholipids → Glycerol-based phospholipids

Glycerophospholipids

• A glycerophospholipid is a lipid that contains two fatty acids and a phosphate

group esterified to a glycerol molecule and an alcohol esterified to the phosphate
group.
Glycerophospholipids

• The alcohol attached to the phosphate group in a glycophospholipid is usually one

of three amino alcohols: choline, ethanolamine or serine.

• Glycerophospholipids containing these three amino alcohols are respectively

known as phosphatidylcholines, phosphatidylethanolamines, and
phosphatidylserines.
• Fatty acid + glycerol + phosphate = phosphatidyl group
Glycerophospholipids

• Glycerophospholipids function almost

exclusively as components of cell membranes
and are not stored.
• The polar head of a glycerophospholipid is
soluble in water, while the nonpolar tail is
soluble in nonpolar substances. This dual
polarity is a structural characteristic of most
membrane lipids.
Glycerophospholipids

• Phosphatidylcholines are also known as lecithins. These are waxy solids that form
colloidal suspensions in water.
• Phosphatidylethanolamines and phosphatidylserines are also known as cephalins.
These compounds are found in heart and liver tissue and in high concentrations in
the brain. They are important in blood clotting.
Sphingophospholipids

• A sphingophospholipid is a lipid that contains one fatty acid and one phosphate
group attached to a sphingosine molecule and an alcohol attached to the
phosphate group.
Sphingophospholipids

• Sphingophospholipids in which the

alcohol esterified to the phosphate group
is choline are called sphingomyelins.
Sphingomyelins are found in all cell
membranes and are important structural
components of the myelin sheath, the
protective and insulating coating that
surrounds nerves.
Sphingoglycolipids

• A sphingoglycolipid is a lipid that contains both

a fatty acid and a carbohydrate component
attached to a sphingosine molecule.
• Sphingoglycolipids undergo saponification
reactions; both the amide and the glycosidic
linkages can be hydrolyzed
Sphingoglycolipids
• The carbohydrate moieties of certain
sphingolipids define the human blood
groups and therefore determine the type of
blood that individuals can safely receive in
blood transfusions.
Sphingoglycolipids

• The simplest sphingoglycolipids called cerebrosides contain a single

monosaccharide unit- either glucose or galactose. Cerebrosides occur primarily in
the brain and in the myelin sheath of nerves.
• More complex sphingoglycolipids, called gangliosides, contain a branched chain
of up to seven monosaccharide residues. These substances occur in the gray
matter of the brain as well as in the myelin sheath.
MEMBRANE LIPIDS:
CHOLESTEROL
Cholesterol

• Cholesterol is a steroid. A steroid is a lipid whose structure is based on a fused

ring system that involves three 6-membered rings and one 5-membered ring.
• Cholesterol is a C27 steroid molecule that is a component of cell membranes and a
precursor for other steroid-based lipids. It is the most abundant steroid in the
human body.
Where do sterols come from?

• The sterols of all eukaryotes are synthesized from simple five-carbon isoprene
subunits, as are the fat-soluble vitamins, quinones, and dolichols

Stigmasterol in plants

Ergosterol in fungi

Bacteria can’t make sterols but some

species can incorporate exogenous sterols
Cholesterol

• Because cholesterol is only sparingly soluble in water (blood), a protein carrier

system is used for its distribution. These cholesterol-protein combinations are
called lipoproteins.
• LDLs (low density lipoproteins) carry cholesterol from the liver to various tissues,
while those that carry excess cholesterol from tissues back to the liver are called
HDLs (high density lipoproteins).
• If too much cholesterol is being transported by LDLs or too little by HDLs, the
imbalance results in an increase in blood cholesterol levels. High blood cholesterol
levels contribute to atherosclerosis, a form of cardiovascular disease characterized
by the buildup of plaque along the inner walls of arteries.
Cholesterol

• Cholesterol are also components of cell membranes. They regulate rigidity by

restricting the movement of fatty acid chains.
Quick Recap: Transport Across Cell Membranes

• Passive transport is the transport process in which a substance moves across a

cell membrane by diffusion from a region of higher concentration to a region of
lower concentration without the expenditure of any cellular energy.
• Facilitated transport is the transport process in which a substance moves across
a cell membrane wit the aid of membrane proteins from a region of higher
concentration to a region of lower concentration without the expenditure of cellular
energy.
• Active transport is the transport process in which a substance moves across a
cell membrane with the aid of membrane proteins against a concentration gradient
with the expenditure of cellular energy.
Quick Recap: Transport Across Cell Membranes
EMULSIFICATION LIPIDS:
BILE ACIDS
Bile acids

• An emulsifier is a substance that can disperse and stabilize water-insoluble

substances as colloidal particles in an aqueous solution.
• Bile acids are cholesterol derivatives that function as lipid-emulsifying agent in the
aqueous environment of the digestive tract.
Bile

• The medium through which bile acids are supplied to the small intestine is bile. It is
a fluid containing emulsifying agents that is secreted by the liver, stored in the gall
bladder, and released into the small intestine during digestion.
• From one-third to one-half of the daily production of cholesterol by the liver is
used to replenish bile acid stores.
• Bile is composed of
- 38% cholic acid derivatives, 34% deoxycholic acid derivatives and 28% 12-
deoxycholic acid derivatives
- also contains bile pigments, cholesterol itself, and electrolytes such as
bicarbonate.

• The bile acids present increase the solubility of the cholesterol in the bile fluid.
Bile

• An increased secretion of cholesterol and

decrease in the size of the bile pool results to
the precipitation of crystallized cholesterol
from the bile and the resulting formation of
gallstones in the gallbladder.
• In Western countries, approximately 80% of
gallstones are almost pure cholesterol.
Other roles of Lipids

• Lipids can also act as signals, cofactors and pigments

Some serve as potent signals—as hormones, carried in the

blood from one tissue to another

intracellular messengers generated in response to an

extracellular signal (hormone or growth factor).

Others function as enzyme cofactors in electron-transfer

reactions in chloroplasts and mitochondria, or in the transfer
of sugar moieties in a variety of glycosylation reactions.
Other roles of Lipids

• Lipids with a system of conjugated double bonds act as pigment molecules that
absorb visible light. Some of these act as light-capturing pigments in vision and
photosynthesis; others produce natural colorations, such as the orange of
pumpkins and carrots and the yellow of canary feathers.
• Finally, a very large group of volatile lipids produced in plants serve as signals that
pass through the air, allowing plants to communicate with each other, and to invite
animal friends and deter foes.
Other roles of Lipids

• Phosphatidylinositols and sphingosine derivatives act as intracellular signals:

- Phosphatidylinositol 4,5-bisphosphate in the cytoplasmic (inner) face of plasma
membranes serves as a reservoir of messenger molecules that are released
inside the cell in response to extracellular signals interacting with specific
surface receptors
Other roles of Lipids
FAT-SOLUBLE VITAMINS
Vitamins are also considered as hormone precursors
Fat-soluble vitamins

• Fat-soluble vitamins were resolved into the four vitamin groups A, D, E, and K, all of
which are isoprenoid compounds synthesized by the condensation of multiple
isoprene units.
Vitamin A

• Vitamin A (retinol), in its various forms, functions as a hormone and as the visual
pigment of the vertebrate eye.
• Acting through receptor proteins in the cell nucleus, the vitamin A derivative
retinoic acid regulates gene expression in the development of epithelial tissue,
including skin.
• Retinoic acid is the active ingredient in the drug tretinoin (Retin-A), used in the
treatment of severe acne and wrinkled skin. Retinal, another vitamin A derivative, is
the pigment that initiates the response of rod and cone cells of the retina to light,
Vitamin A

• Vitamin A was first isolated from fish liver oils; liver, eggs, whole milk, and butter are
also good dietary sources. In vertebrates, β-carotene, the pigment that gives
carrots, sweet potatoes, and other yellow vegetables their characteristic color, can
be enzymatically converted to vitamin A.
• Deficiency: Deficiency of vitamin A leads to a variety of symptoms in humans,
including dryness of the skin, eyes, and mucous membranes; retarded
development and growth; and night blindness, an early symptom commonly used
in diagnosing vitamin A deficiency
Vitamin D

• Vitamin D3, also called cholecalciferol

• Normally formed in the skin from 7-dehydrocholesterol
• Vitamin D3 is not itself biologically active, but it is converted by enzymes in the liver
and kidney to 1α,25-dihydroxyvitamin D3 (calcitriol), a hormone that regulates
calcium uptake in the intestine and calcium levels in kidney and bone
• Deficiency of vitamin D leads to defective bone formation and the disease rickets,
for which administration of vitamin D produces a dramatic cure . Vitamin D2
(ergocalciferol) is a commercial product formed by UV irradiation of the ergosterol
of yeast.
Vitamin D

• Dietary vitamin D prevents

rickets, a disease once
common in cold climates
where heavy clothing blocks
the UV component of sunlight
necessary for the production of
vitamin D3 in skin. On the left
is a 21⁄2-year-old boy with
severe rickets; on the right, the
same boy at age 5, after 14
months of vitamin D therapy.
Vitamin E

• Vitamin E is the collective name for a group of closely related lipids called
tocopherols, all of which contain a substituted aromatic ring and a long isoprenoid
side chain
Vitamin K

• The aromatic ring of vitamin K under goes a cycle of oxidation and reduction during
the formation of active prothrombin, a blood plasma protein essential in blood
clotting. Prothrombin is a proteolytic enzyme that splits peptide bonds in the blood
protein fibrinogen to convert it to fibrin,
• Vitamin K deficiency is very uncommon in humans, aside from a small percentage
of infants who suffer from hemorrhagic disease of the newborn, a potentially fatal
disorder. In the United States, newborns are routinely given a 1 mg injection of
vitamin K.
Vitamin K

• Vitamin K is one of the treatments for bleeding events caused by overdose of the
anticoagulant drug warfarin (Coumadin®).
• Vitamin K is also part of the suggested treatment regime for poisoning by
rodenticide (coumarin poisoning)
• Oral Vitamin K1 is preferred over other routes of administration because it has less
side effects.
• Forms of Vitamin K:
- Vitamin K1 (phylloquinone) is found in green plant leaves;
- a related form, vitamin K2 (menaquinone), is formed by bacteria living in the
vertebrate intestine.
- Menadione → Vit. K3
MESSENGER LIPIDS:
STEROID HORMONES
Steroid hormones

• A hormone is a biochemical substance produced by a ductless gland, that has a

messenger function, serving as a means of communication between various tissue.
Most hormones, though not all, are lipids.
• A steroid hormone is a hormone that is a cholesterol derivative. There are two
major classes of steroid hormones:
(1) sex hormones – control reproduction and secondary sex characteristics
(2) adrenocorticoid hormones – regulate biochemical processes in the body
• Steroid hormones move through the bloodstream (on protein carriers) from their
site of production to target tissues, where they enter cells, bind to highly specific
receptor proteins in the nucleus, and trigger changes in gene expression and thus
metabolism.
Sex Hormones

• The sex hormones can be classified into three major groups:

- Estrogens → the female sex hormones
- Androgens → the male sex hormones
- Progestins → the pregnancy sex hormones

• Estrogens are synthesized in the ovaries and adrenal cortex and are responsible
for the female sex characteristics at the onset of puberty and for regulation of the
menstrual cycle
• Androgens are synthesized in the testes and adrenal cortex and promote the
development of secondary male characteristics
• Progestins are synthesized in the ovaries and placenta and prepare the lining of
the uterus for implantation of the fertilized ovum. They also suppress ovulation
• Increased knowledge of the structures and functions of sex hormones has led to
the development of a number of synthetic steroids whose actions often mimic
those of the natural steroid hormones.

The best known types of synthetic steroids are oral contraceptives and anabolic
steroids.
Anabolic steroids

• Anabolic steroids include the illegal steroid drugs used by some athletes to build
up muscle strength and enhance endurance. Such steroids are now known to have
serious side effects in the user. It is close to the naturally occurring testosterone.
Anabolic steroids

• Testosterone is the template for synthetic anabolic steroids

• Testosterone derivatives increase the body’s ability to metabolize ingested protein

and facilitate the synthesis of new skeletal muscle proteins
Adrenocorticoid Hormones

• Produced by the adrenal glands, at least 28 different hormones have been isolated
from the adrenal cortex. There are two types of adrenocorticoid hormones:
(1) Mineralocorticoids – control the balance of Na+ and K+ ions in cells and body fluid
(2) Glucocorticoids – control glucose metabolism and counteract inflammation

• The major mineralocorticoid is aldosterone, and the major glucocorticoid is

cortisol.
• Cortisol is the hormone synthesized in the largest amount by the adrenal glands.
Cortisol and its ketone derivative cortisone exert powerful anti-inflammatory effects
in the body.
Too little or too much Cortisol

• Cortisol is often called the “stress hormone”, as this hormone is released during
times of stress, increasing heart rate, blood pressure, blood glucose, respiration
and muscle tension.
• Addison's disease is an endocrine disorder characterized by inadequate
production of glucocorticosteroids (cortisol) and, sometimes,
mineralocorticosteroids by the adrenal gland.
• Cushing’s disease is a specific type of Cushing’s syndrome caused by a pituitary
tumor leading to excessive production of ACTH (adrenocorticotropic hormone).
Excessive ACTH stimulates the adrenal cortex to produce high levels of cortisol,
producing the disease state.
MESSENGER LIPIDS:
EICOSANOIDS
Eicosanoids

• An eicosanoid is an oxygenated C20 fatty acid derivative that functions as a

messenger lipid. The metabolic precursor for most eicosanoids is arachidonic
acid, the 20:4 fatty acid.
• Eicosanoids are hormone-like molecules rather than true hormones because they
are not transported in the bloodstream to their site of actions. Instead, they exert
their effects in the tissues where they are synthesized.
• Eicosanoids usually have a very short “life”, being broken down, often within
seconds of their synthesis to inactive residues which are eliminated in urine.
Eicosanoids

• The physiological effects of eicosanoids include mediation of

(1) The inflammatory response
(2) The production of pain and fever
(3) The regulation of blood pressure
(4) The induction of blood clotting
(5) The control of reproductive functions, such as induction of labor
(6) The regulation of the sleep/wake cycle

There are three principal types of eicosanoids: prostaglandins, thromboxanes and

leukotrienes.
Prostaglandins

• A prostaglandin is a messenger lipid that is a C20 fatty acid derivative that

contains a cyclopentane ring and oxygen-containing functional group.
• Prostaglandins are involved in many regulatory functions, including raising body
temperature, inhibiting the secretion of gastric juices, increasing the secretion of a
productive mucus layer into the stomach, relaxing and contracting smooth muscle,
directing water and electrolyte balance, intensifying pain and enhancing
inflammation responses.
• Aspirin works by reducing inflammation and fever because it inactivates the
enzyme needed for prostaglandin synthesis.
Thromboxanes

• A thromboxane is a messenger lipid that is a C20 fatty-acid derivative that

contains a cyclic ether ring and oxygen-containing functional groups.
• An important function of thromboxanes is to promote the formation of blood clots.
Thromboxanes are produced by blood platelets and promote platelet aggregation.
Leukotrienes

• A leukotriene is a messenger lipid that is a C20-fatty acid derivative that contains

three conjugated double bonds and hydroxy groups.
• Leukotrienes are found in leukocytes (white blood cells). Their source and the
presence of the three conjugated double bonds account for their name.
• They are powerful biological signals. For example, leukotriene D4, derived from
leukotriene A4, induces contraction of the smooth muscle lining the airways to the
lung.
• The overproduction of leukotrienes causes asthmatic attacks, and leukotriene
synthesis is one target of antiasthmatic drugs such as prednisone. The strong
contraction of the smooth muscle of the lungs that occurs during anaphylactic
shock is part of the potentially fatal allergic reaction in individuals hypersensitive to
bee stings, penicillin, or other agents.
PROTECTIVE-COATING LIPIDS:
BIOLOGICAL WAXES
Biological waxes

• A biological wax is a lipid that is a monoester of a long-chain fatty acid and a long-
chain alcohol.
Biological waxes

• Their melting points (60 to 100 C) are

generally higher than those of
triacylglycerols.
• Waxes serve a diversity of other
functions related to their water-repellent
properties and their firm consistency
(e.g. makes bird feather shiny, plant
surfaces shine)
Biological waxes

• The water-insoluble, water repellent properties of biological waxes result from the
complete dominance of nonpolar nature of long hydrocarbon chains present over
the weakly polar nature of the ester functional group that links the two carbon
chains together.
• Both humans and animals possess skin glands that secrete biological waxes to
protect hair and skin and to keep it pliable and lubricated .
Biological waxes

• Biological waxes find use in pharmaceuticals, cosmetics and polishing industries.

• Biological waxes find a variety of applications in the pharmaceutical, cosmetic, and
other industries. Lanolin (from lamb’s wool), beeswax , carnauba wax (from a
Brazilian palm tree), and wax extracted from spermaceti oil (from whales) are
widely used in the manufacture of lotions, ointments, and polishes
•
References

• Stoker, H. General, Organic and Biological Chemistry, 5th Ed.