Chapter 3: LIPIDS

Definition:

A heterogeneous group of organic compounds, including fats, oils, steroids, waxed, and related compounds.

Lipids serve adverse functions in the human body.

 Efficient energy-store
 Electrical insulation of nerves
 Thermal insulation
 Cell membrane constituent

Classification:

1. Simple Lipids are esters of fatty acids with various alcohols

a. Fats: Ester of fatty acids and glycerol
b. Oils: Fats in the liquid state
c. Waxes: Esters of fatty acids with higher molecular weight alcohols.

2. Complex lipids are esters of fatty acids, which contain an alcohol and one or more fatty acid acids, and
another group.
a. Phospholipids contain a phosphoric acid residue, and the fatty acid can be glycerol
(glycerophospholipid) or sphingosine (sphingophospholipid)
b. Glycolipids contain a fatty acid, sphingosine and a carbohydrate.
c. Other complex lipids like lipoproteins and sulpholipids.

3. Derived lipids are formed from the hydrolysis of simple and complex lipids
a. Fatty acids
b. Glycerol (and other alcohols)
c. Steroids/Sterols
d. Fat-soluble Vitamins
e. Ketone bodies
f. Carotenoids

This diagram is not

inclusive
 Simple lipids are composed of an alcohol and 3 fatty acids joined by ester linkage.

If the alcohol is glycerol then we are talking about fats, aka, triacylglycerol.

 Triacylglycerols make around 90% of the total lipid content of our diet and 100% of animal and plant fats.
 They are stored mainly in the cytoplasm of adipose cells, found subcutaneously and surrounding body
organs like the liver.
 Body fat is an important source of energy.

Ester
link

Here R1, R2 and R3 correspond to fatty acids.

Triacylglycerol

Alcohols
The two most common alcohols correlated with lipids in our body are glycerol and cholesterol. Higher mass
number alcohols are found in wax.

Glycerol is a three carbon alcohol that contains three –OH groups (trihydric alcohol), giving it the ability to
join 3 fatty acids.

Characteristics: It is colorless, odorless, and soluble in both water and polar solvents.

USES: Glycerol is used in manufacturing creams and lotions and used as a drug for coronary dilation.

Cholesterol will be discussed in derived lipids.

Fatty acids
A fatty acid is a long chain carboxylic acid. In other words, a long chain organic molecule containing a
carboxylic acid group. They are usually aliphatic and mono-carboxylic. Occur mainly as ester in fats or found free
in blood plasma

Fatty acids can be saturated or unsaturated.

(a) Is a saturated fatty acid

(b) Is an unsaturated fatty acid in cis- configuration.

What does this mean?

Cis-configuration means the double bond curls the fatty acid

inwards. The opposite would be trans-configuration, where the
double bond curls the fatty acid outwards.

Double bonds in fatty acids are nearly always in cis configuration,

and are placed in 3 carbon intervals (at the 9th, 12th and 15th carbons,
for example.)
 Saturated vs unsaturated

Saturated fatty acids contain no double bonds and are non-essential to our diet as the body can produce
them.

Unsaturated fatty acids contain a double bond.

 Monounsaturated fatty acids contain one double bond and are non-essential.
 Polyunsaturated fatty acids contain 2 or more double bonds and are
essential.
o Also called polyenoic fatty acids.

Fats rich in unsaturated fatty acids (like olive oil) are liquid at room
temperature, whereas those with a higher content of saturated fatty acids (like
butter) are more solid.

A simplified nomenclature for unbranched fatty acids specifies the chain length and number of double
bonds, separated by a colon.

 16-carbon saturated palmitic acid is 16:0

 18-carbon oleic acid, with one double bond, is 18:1.

Table of the most common, naturally occurring, fatty acids

Only the carbon skeleton and

Common name are important in this table.

“Δ9” means a double bond is present

at the 9th carbon.
 Saturated fatty acids elevate cholesterol level in the blood and are oxygenated less rapidly than unsaturated
fatty acids and thus are considered less healthy than unsaturated fatty acids.

There are two systems for naming unsaturated fatty acids.

1. Omega system where the first carbon is the one

furthers from the –COOH group.
 Linoleic acid 18:2 Δ9, 6
2. Delta system where the first carbon is that of the –
COOH group.
 Linoleic acid 18:2 ω-3

Essential vs nonessential

Essential fatty acids are those that have double bonds after the 9th delta carbon, as the body lacks the
enzyme needed to introduce double bonds after carbon 9.

Essential fatty acids must be supplied in the diet, they are mainly present in vegetable oils and fish oils. And
they are synthesized by plants.

Essential fatty acids

Arachidonic fatty acid is synthesized in the Type ω-3 ω-6
body by linoleic acid and only becomes essential if
linoleic acid is deficient.
Linolenic acid 18:3 Δ9, 12, 15 Linoleic acid 18:2 Δ9, 12
Fatty
acid Clupanodonic acid 22:5 Δ7, Arachidonic acid 20:4
10, 13, 16, 19
Δ5, 8, 11, 14

- Functions of essential fatty acids

1. Needed for normal growth
2. Help maintain fluidity of cellular membranes
3. Precursors for arachidonic acid (linoleic acid) from which the eicosanoids (e.g. prostaglandins) are
derived
4. Polyunsaturated fatty acids are Atheroprotective, which means they prevent atherosclerosis (narrowing
of blood vessels).

The opposite would be saturated fatty acids which are Atherogenic, the cause atherosclerosis

Non-essential fatty acids can be synthesized by the body either from other fatty acids or from other food
derived precursors.

Eicosanoids
Eicosanoids are a subcategory of unsaturated fatty acids. They are cyclic compounds derived from
arachidonic acid 20:4 after its cyclization. The two main groups are:

1. Prostanoids
a. Prostaglandins (PGs): exist in all mammals and have a local hormone-like action. They can cause
vasodilation and uterine or intestinal contraction.
b. Prostacyclins (PCIs): inhibits platelet activation and is also an effective vasodilator
c. Thromboxanes (TXs): cause platelet aggregation
2. Leukotrienes (LTs) are proinflammatory agents present in leukocytes, platelets and mast cells. They cause
leukocytes to collect at the site of inflammation (chemotaxis.)

Properties of fatty acids

Physical and physiological properties of fatty acids reflect chain length and degree of
unsaturation.
Shorter chain fatty acids tend to be
o more soluble in water
o Have lower melting point (liquid in room
temperature).

Higher degree of unsaturation of a fatty acid means it

has a lower melting point.
Animal triacylglycerols c0ntain around 50%
unsaturated fatty acid content while plant
triacylglycerols contain around 85% unsaturated fatty
acid content. Thus, plant fats have a lower melting point
and are liquid in room temperature (are oils) and animal fats have a higher melting point and are solid in room
temperature (fats).

Chemical properties of fatty acids.

Fatty acids can be 1. Hydrogenated (addition of hydrogen) or 2. Halogenated (addition of a halogen like
chlorine), to remove double bonds, converting unsaturated fatty acids to saturated fatty acids. They can also be
3. Oxidized to convert unsaturated fatty acids to peroxides.
Hydrogenation is the most common process, used in the production of margarine from vegetable oil.
Margarine is considered to be healthier than butter.

Rancidity is the toxic reaction of triacylglycerols, it is caused by the oxidation of its unsaturated fatty acids
by bacteria or just oxygen in the air/moisture. It leads to unpleasant taste and odor of the fat, (basically the fat
going bad).

Also called complex lipids or conjugated lipids

Compound lipids are esters of fatty acid with an alcohol AND other groups. The two major groups of compound
lipids are Phospholipids, Glycolipids and Lipoproteins.
 Phospholipids
Phospholipid are lipid molecules that contain a phosphate molecule (H3PO4) attached to the alcohol. The alcohol
can be either glycerol (making glycero-phospholipids) or sphingosine (making sphingo-phospholipids).

Functions of phospholipids in the body:

1. Form cell membranes

2. Absorption of lipids from intestines
3. Components of lipoproteins
4. Solubilize cholesterol in bile
5. Have a role in blood coagulation process
6. Have a role in signal transmission across cell membranes

Glycerophospholipids

Are derivatives of Phosphatidic acid.

Phosphatidic acid, aka diacylglycerol phosphate, is a glycerol molecule esterified with:

 a saturated fatty acid at C1 Organic structure of one molecule

of phosphatidic acid;
 an unsaturated fatty acid at C2
a) Acyl chains;
 a phosphate at C3
b) Glycerol backbone;
c) Phosphate group;
The carbon molecules of glycerol
are numbered in blue.
It is formed during synthesis of triglycerides and phospholipids.

Different glycerophospholipids are made by attaching different alcohols or amino-alcohols to the phosphate at
carbon 3.

The ones we are going to discuss are Cardiolipin, Lecithin, Cephalin, Phosphatidyl Serine and Phosphatidyl
Inositol.

1. Cardiolipin
Di-phosphatidyl Glycerol.

Structure: Two phosphatidic acids linked together by a glycerol.

Function:
 major component lipid of mitochondrial membranes
 Antigenic (can stimulate antibody formation)

2. Lecithin
Phosphatidyl choline
Structure: Phosphatidic acid and choline amino alcohol attached to the
phosphate group
Function:
 Major component lipid of mitochondrial membranes
 Antigenic (can stimulate antibody formation)
 Can form cholesterol ester
  Acts as a store of Choline, choline is a methyl donor in transmethylation reactions.
 Solubilizes cholesterol (prevent cholesterol gall stones)
 Di-palmityl-lecithin is a lung surfactant continuously produces by alveolar cells. It prevents lung
collapse.
 Lysolecithin is similar in lecithin in structure but lacks the unsaturated fatty acid on carbon 2, it
is important in metabolism and making of phospholipids.
 Plasmalogen is similar to lecithin in structure but has an unsaturated fatty acid on carbon 1, it
contributes to 10% of the phospholipids in the brain and muscles.

Clinical application: Respiratory Distress Syndrome

Hyaline membrane disease that occurs in babies where the lungs do not secrete enough surfactant, leading to lung
collapse and respiratory failure.

3. Cephalin
Phosphatidyl Ethanolamine

Structure: Phosphatidic acid and ethanolamine amino alcohol attached to the

phosphate group
Function:
 Activating factor of coagulation mechanism
 Lysocephalin is similar to Cephalin in structure but lacks the
unsaturated fatty acid on carbon 2 (just like lysolecithin). It is a
strong surface-active substance, used in manufacturing most types of chocolates.

4. Phosphatidyl Serine
Phosphatidyl Serine

Structure: Phosphatidic acid and serine amino alcohol attached to

the phosphate group

Serine, ethanolamine and choline

 Ethanolamine is decarboxylated serine.

 Choline is tri-methylated ethanolamine.

5. Lipositol
Phosphatidyl Inositol

Structure: Phosphatidic acid and inositol cyclic sugar alcohol attached to the phosphate group
Function:
 Present in cell membranes
 Precursor of the secondary messenger Inositol Triphosphate, so plays a role in mediating
hormonal action.
Glycerophospholipids table.

SphingoPhosopholipid

Only one exists and it’s called sphingomyelin.

 It is a phospholipids where the alcohol is not glycerol but Sphingosine.

 Present in high concentration in the brain and nerves

Structure: Ceramide (sphingosine + Fatty acid),

phosphate and choline.

Sphingosine is a complex 18 carbon amino-alcohol and is a constituent of both phospholipids and glycolipids.
Lipids that have sphingosine are called sphingolipids.

Medical application: Niemann Pick’s disease

Disease caused by the accumulation of large amount of sphingomyelin due to the lack of the enzyme
sphingomyelinase. Symptoms are mental retardation and early death.
 Glycolipids

Glycolipids (glycosphingolipids) are lipids with an attached carbohydrate or carbohydrate chain. They are
widely distributed in every tissue in the body, particularly in nervous tissue such as brain.

The glycolipids we are going to discuss are Cerebrosides, Gangliosides, Sulphatides (sulpholipids),
Globosides and Ceramide oligosaccharides.

1. Cerebrosides
The simplest glycolipid.

Structure: Ceramide (sphingosine and fatty acid) and

a single sugar residue (glucose or galactose)

Function: acts as a nerve impulse insulator in the

white matter or the brain and myelin sheath of
nerves.

Based on the fatty acid in the ceramide molecule, different Cerebrosides are made:

Fatty acid Cerebroside

Lignoceric acid Kerasin
Cerebronic acid Cerebron
Nervonic acid Nervon
Oxynervonic acid Oxynervon

2. Gangliosides
Gangliosides are mole complex glycolipids, with an oligosaccharide fragment attached to the ceramide
molecule.

Structure: Ceramide (sphingosine and fatty acid) and

number of sugar groups, hexose-amine and sialic acid.

Function: abundant in grey matter at nerve ending and

has function in cell communication and molecular
recognition.

Because of the recognition related functions, gangliosides are concentrated in the outer leaflet of the cell
membrane

3. Sulphatides
Also called sulpholipids, are Cerebrosides containing a sulfate group attached to the sugar.
They are abundant in white matter of the brain.
 Structure: Ceramide (sphingosine and fatty acid) and a single sugar residue (glucose or galactose) with a
sulfate group attached

4. Globosides
Globosides are glycolipids with two or more sugars attached to the ceramide molecule, usually glucose
galactose. (Similar to Cerebrosides)

Function: they play roles in cell recognition, signaling, and adhesion.

5. Ceramide oligosaccharides
A broad category of glycosphingolipids that include any glycosphingolipids with oligosaccharide chains.
 Lipoproteins
Lipoproteins are complex particles composed of lipids and proteins that play a crucial role in the
transportation of lipids through the blood, and they are also found in cell membranes.

Lipoproteins are named according to their density, which increases with the percentage of protein in the
particle.

Types: from least to most dense

 Chylomicrons
 VLDL (very low density lipoprotein)
 LDL (low density lipoprotein)
 HDL (high density lipoprotein)

Lipid Protein
Lipoprotein Function
content content
Transport dietary triglyceride and cholesterol from
Chylomicrons 98% 2%
intestine to tissues
VLDL Transports triglyceride from liver to tissues 90% 10%
LDL Delivers cholesterol into cells 78% 22%
Picks up cholesterol accumulating in blood vessels and
HDL 50% 50%
delivers it to liver for elimination

Lipoproteins can be separated by electrophoresis and by ultracentrifugation.

Ultracentrifugation separated them into: While Electrophoresis separated them into:

- Chylomicrons - Chylomicrons
- VLDL - β-Lipoprotein
- LDL - Pre β-Lipoprotein
- HDL - α-Lipoprotein

Clinical application: Good vs Bad cholesterol

Chylomicrons, VLDL and LDL are Atherogenic lipoproteins, which means they prevent atherosclerosis (narrowing
of blood vessels).
HDL is Atheroprotective lipoprotein.
 Derived lipids is a group of compounds formed from simple and complex lipids through the process of
hydrolysis, and compounds associated with lipids in nature (miscellaneous lipids).

Derived lipids include:

 All hydrolytic products of simple and conjugated lipids

o Glycerol
o Fatty acids
o Monoglycerides
 Steroids
o Sterols
o Bile acids
o Steroid hormones
o Vitamin D
 Carotenoids
 Ketone bodies
 Fat soluble vitamins (ADEK)

Derived lipids have functions in cell signaling and communication, structures of cell membranes and can
be metabolic intermediates.

Steroids
A steroid is any compound that contains a steroid nucleus.

A steroid nucleus is three cyclohexane rings (Phenantherene) and one

cyclopentane ring fused together, in other words Cyclopentano-
Perhydro-Phenantherene Ring

A sterol is essentially a steroid alcohol.

The steroids we are going to discuss are Cholesterol, Ergosterol, Vitamins D2 and D3, Bile salts and
acids, and Steroid hormones.

1. Cholesterol
Cholesterol is an animal sterol (alcohol) that is an integral component of animal cell membranes, and it
serves as a precursor for the synthesis of steroid hormones, bile acids, and vitamin D.

Structure:
Steroid nucleus with:

 2 methyl groups at carbons 10 and 13

 An –OH group at carbon 3 (only polar group)
 A double bond between carbons 5 and 6
 8 carbon alkyl side chain at carbon 17
 Cholesterol is a non-polar molecule (with the only polar group being the –OH) so it is insoluble in water.

Function:
 Integral part of cell membranes and helps maintain
membrane fluidity
 Precursor of:
o Vitamin d3
o Steroid hormones
o Bile acids
 It transports long chain fatty acids
 Has insulating effect in the CNS and makes the skin water-resistant.

Sources:
Cholesterol can be obtained by two ways.

1. Exogenous, where is it taken in by being part of the diet. It is present especially in butter, milk
products, eggs, and meat.
2. Endogenous, where it is synthesized in body tissues like the liver. (1 gram/day)

Forms:
Cholesterol in the blood can take one of two forms:

1. Free (30%)
2. Esterified (70%), where it is bonded to a long chain fatty acid by its –OH at carbon 3.

Coprastanol is the name of the form cholesterol takes in the smack intestines. There, it is reduced
(reduction of the double bond between carbons 5 and 6) by bacteria flora before its excretion.

Clinical application: Good vs Bad cholesterol

The normal plasma cholesterol level is less than 220 mg/dL.

2. Ergosterol
Ergosterol is plans’ sterol. It is similar to
cholesterol in structure but only differs in:

 Having an extra double bond between

carbons 6 and 7
 Side chain is unsaturated and has
extra methyl group.

Ergosterol is the precursor of vitamin D2.

3. Vitamins D2 and D3

They are formed by the rupture of the second ring of ergosterol (Vitamin D2) and cholesterol (Vitamin
D3) by UV radiation.

4. Bile acids and Bile salts

Bile acids are derivatives of the 24 carbon steroid acid, cholanic acid. They can be primary or secondary.

 Primary Bile Acids: Synthesized in the liver from cholesterol. The main primary bile acids in
humans are:
o Cholic acid: 3, 7, 12 TriHydroxy Cholanic acid
o Chenodeoxycholic acid: 3,7 Dihydroxy Cholanic

 Secondary Bile Acids: Formed by bacterial action in the colon. The main secondary bile acids in
humans are
o Deoxycholic acid: 3, 12 Dihydroxy Cholanic acid
o Lithocholic acid: 3 Monohydroxy Cholanic acid

Bile salts are produced from bile acids by conjugating them with taurine or glycine. They are produced in
the liver and released into the intestine. There, they have important functions:

 Emulsification of fat
 Way of excretion of cholesterol
 Participate in forming Micelle (the from fat takes during absorption)

Afterwards, a large portion of bile acids is reabsorbed in the ileum and returned to the liver via the portal
circulation, a process known as enterohepatic circulation.
5. Steroid hormones
Hormones are chemical messengers. One group of hormones is called steroid hormones because they are
synthesized from the steroid cholesterol.

The two main groups of steroid hormones are sex hormones and adrenocortical hormones.

1. Sex hormones
The sex hormones are a class of steroid hormones secreted by the gonads (ovaries or testes), the
placenta, and the adrenal glands.

Both males and females produce androgens and estrogens, differing in the amounts of secreted hormones
rather than in the presence or absence of one or the other.
 Male sex hormones (androgens):
1. Testosterone
And Dihydrotestosterone (DHT)

DHT is the active form of testosterone in tissues.

Functions:

 Production of sperm
 Responsible for the development of secondary male characteristics
 Have anabolic effect on proteins

Excretion:

Androgens are converted to 17-keto steroids which is excreted in urine

Clinical application: urinary 17-keto steroids

Increased urinary 17-keto steroid levels can be caused by diseases like testicular tumors
Decreased urinary 17-keto steroid levels can be caused by diseases like hypogonadism

Female sex hormones:

Two kinds of sex hormones are of particular importance in females: progesterone and the estrogens

1. Estrogen
Forms:

- Estrone E1
- Estradiol E2 (most active)
- Estriol E3
-

Produced in the ovary and placenta and minor amounts in the adrenal cortex and testes in males.

Functions:

 Responsible for the development of female primary and secondary sexual characteristics
 E2 has an anabolic effect on bones and cartilage.
 Can be synthetically made and used as contraceptive

Excretion:

E3 is the end product produced in the liver, conjugated with acids and excreted in urine.

2. Progesterone
Functions:

 Prepares the uterus for pregnancy

 Prevents the further release of eggs from the ovaries
during pregnancy
 Stabilizes pregnancy
 Inhibits milk production in late pregnancy
 Produced in the ovary and placenta and minor amounts in the adrenal cortex and testes in males.

Excretion:

Pregnadiol is the end product produced in the liver, conjugated with acids and excreted in urine.

Both males and females produce androgens and estrogens, differing in the amounts of secreted
hormones rather than in the presence or absence of one or the other.

2. Adrenocortical hormones

Adrenocortical hormones are a group of steroid hormones, derived

from cholesterol by the adrenal cortex, which is the outer layer of the
adrenal glands located on top of each kidney.

These hormones play crucial roles in regulating metabolism, immune response, blood pressure, and other
essential physiological functions.

Can be categorized into glucocorticoids and mineralocorticoids.

Glucocorticoids

- Corticosterone
- Cortisol
- Cortisone
- 11-dehydrocorticosterone

Glucocorticoids control the metabolism of carbohydrates, lipids and proteins.

Mineralocorticoids

- Aldosterone
- Deoxycorticosterone (DOC)

Mineralocorticoids control the metabolism of minerals and act mainly on the kidneys.