LIPIDS

LIPIDS CHEMISTRY
Muhammad Hassan Yankuzo (MBBS,
PhD)
 Outline
 Overview of Lipids
 Classification
 Functions & Clinical Significance
 Chemistry and properties
 Fatty Acids, TGs, PLPs, Waxes, & PGs
 Lipid micelles, monolayers & bilayers
 Sterols
 Lipoprotein system
 LIPIDS
 Lipids are heterogeneous
organic substances that
are relatively insoluble in
water (hydrophobic) but
soluble in organic sol-
vents (benzene, chloro-
form, ethanol, ether,
CCL4, acetone, etc)

 Lipids consist of alcohol

and fatty acids joined
 Functions of lipids
1. Reservoir of energy e.g. Triglycerides - 9

Kcal/g; supplies 60% of body’s energy

need

2. Important constituents of cell membrane

e.g. phospholipids, cholesterol

3. As insulators on the neurons e.g. myelin

6. Act as surfactants, detergents and emulsifying

agents e.g. lecithin, sphingomyelin, bile acid,

e.t.c.

7. Helps in the regulation of metabolic processes.

e.g.

steroid hormones, prostaglandins

8. Contributes flavor, aroma and palatability of

foods
 Clinical significance of
lipids
To know the diseases associated with
abnormal metabolism of lipids such as:
 Obesity
 Atherosclerosis
 Hyperlipidemia/Hypercholesterolemia
 Diabetes mellitus
 Fatty liver
 Lipid storage diseases e.g. Gauchers,
Niemann-Pick, Fabry’s & Tay-Sach’s dis-
eases
CLASSIFICATION OF LIPIDS

Phospholipids, glycol- steroids,

TGs & ipids (cerebroside, cholesterol,
globoside, ganglio-
waxes PGs,
side), sulpholipids & leukotrienes
lipoproteins
I. Simple lipids
a. Triacylglycerol/triglycerides/neutral fats
b. Waxes: esters of FA with alcohol
II. Compound lipids
1. Phospholipids
a. Nitrogen containing phospholipids: lecithin,
cephaline, phosphatidyl serine

b. Non-nitrogen containing phospholipids:

phosphatidyl inositol, phosphatidyl glycerol,
cardiolipin (diphosphatidyl glycerol)
 c. Plasmalogens: lipids with long
chain alcohol. e.g. choline &
ethanolamine.
d. Phosphosphingosides: e.g.
sphingomyelin

2. Non-phosphorylated lipids. Examples

a. Glycolipids: e.g. cerebrosides,
globosides, gangliosides

b. Sulpholipids: e.g. Sulphated

glycolipids
III. Examples: steroids including
cholesterol, prostaglandins,
leukotrienes, terpenes, etc

IV. Lipids conjugated with other

compounds: e.g. lipoproteins,
glycolipids, etc
 EXAMPLES OF
LIPIDS

1. Triglycerides

2. Phospholipids

3. Steroids (cholesterol & others)

TRIGLYC-
ERIDES
 TRIGLYCERIDES
Esters of FAs with alcohol
Predominant form of fat in foods and
major fuel store in the body
Sources – exogenous ie. Dietary (90%
of 60 -150g adult lipid intake per day), and
endogenous (mainly by liver & adipose tissue)
Structure – composed of 3 fatty acids + glycerol
Structure of a Triglyceride
 Fatty Acids
Organic acids (chain of carbons with
hydrogen attached) that have acid
group at one end & a methyl group at
the other end
 Fatty Acids
 Most common components of lipids
 Exist as esters on different classes of
lipids
 In humans FFAs are formed only during
metabolism
 FAs are aliphatic carboxylic acids with

general structure of R--COOH

 Hydrogenation: UFA can be converted
,.

to SFA
Halogenation:UFA react with halogens
such as l2
3. Melting point: increases with increase
in chain length. Short and medium
chain have lower melting point than
long chain
f

Salt formation: UFA & SFA can form •

salts (soaps) with Na ,K, Ca or Mg
 Ester formation: UFA & SFA react with alcohol
especially glycerol to form esters

Glycerol + FA - monoacyl glycerol

Monoacyl glycerol + FA - diacyl glycerol
Diacyl glycerol + FA - triacy!glycerol

6. Oxidation: FA can undergo oxidation to

generate energy in ~-oxidation. But UFA can
.> undergo auto-oxidation due to C=C - rancidity
Classification of FAs
Common FAs and their characteristics

as above
as above

as above
as above
as above

as above as above
as above
Common FAs and their characteristics
Saturated fatty acid – Carbon
chains filled with hydrogen
atoms (i.e. no double bond).
Saturated fats appear solid at
room temperature. Examples:
acetic acid, palmitic acid, bu-
tyric acid & stearic acid
 Saturated FA (SFA)
 Carbon chains filled with H atoms (i.e.
no double bond)
 Have general formula CH3-(CH2)n-COOH
 Appear solid at room temperature
 Examples:
 Acetic acid CH3-COOH
 Butyric acid CH3-(CH2)2-COOH
 Palmitic acid CH3-(CH2)14-COOH
 Stearic acid CH3-(CH2)16-COOH
 Saturated FA (SFA)
 Acetic and butyric acids are important meta-
bolic
intermediates

 The palmitic and stearic acids are most

abundant in
body fat

 Human body fat consists of 50% oleic, 25%

palmitic, 10% linoleic and 5% stearic

 Carbons are numbered 1,2,3… starting from

 Unsaturated FA (UFA)
 They have C=C double bond
 Liquid at room temperature
 The higher the C=C bonds the more
liquid they are
 Are similar to saturated FAs by reaction
at COOH group but exhibit isomerism
at C=C
 Naturally exist as cis isomers, but dur-
ing metabolism trans isomers may be
formed

 Unsaturated FA (UFA)
Oleic acid – 18-carbon, monounsaturated

Polyunsaturated FA
 Location of double bonds

Omega number – refers to the

position of double bond nearest
the methyl (CH3) end of the car-
bon chain
Example is seen in 2 essential
PUFAs

Omega-3 fatty acid

Omega-6 fatty acid
FA composition of some common Oils
 Omega-3 Vs Omega-6 Fatty Acids

Carbons are numbered 1,2,3 starting from COOH end, and Omega 1,2,3 start-
ing from omega carbon (CH3) end
 Essential Fatty Acids

Linolenic and Linoleic acids are

essential FAs because they cannot be
synthesized by the body

Arachidonic acid – a semi essential FA,

becomes essential only when its’
precursor (linoleic acid/Omega-6 FA) is
not provided
 Functions of essential FAs
As components of phospholipids in the cell
membrane

Synthesis of eicosanoids (potent hormone

like chemicals such as PGs & leukotrienes)

 Omega-3 produce eicosanoids that lowers

 BP by regulating SMs contraction

 Omega-3 eicosanoids decreases blood clotting

& viscosity, thereby reducing the risk of CHDs,
 Arthritis & cancer
Copyright 2005 Wadsworth Group, a division of Thomson Learning
Hydrogenation of PUFA
 Advantage
 Hydrogenation produces more chemically sta-
ble fats in food industries that resists oxida-
tion and rancidity (i.e. increase food shelf life).
Processing of margarine, peanut butter, baked
goods & Snacks


Disadvantage:

- Generation of less healthy trans-fats which

raises LDL-C (bad cholesterol) possibly by
decreasing the LDL receptor activity thereby
increasing the risk of developing CHDx
 Cis Vs Trans Fats

 In nature, most double bonds are cis;

meaning that hydrogens next to the
double bonds are on the same side of
the carbon chain
When a fat is partially hydrogenated,
some of the double bonds change from
cis to trans
Cis Vs Trans Fats
Copyright 2005 Wadsworth Group, a division of Thomson Learning
Copyright 2005 Wadsworth Group, a division of Thomson Learning
Comparing
Comparing Butter
Butter &
& Margarine
Margarine Labels
Labels
Cutting Fat Cuts Calories and Saturated Fat

Copyright 2005 Wadsworth Group, a division of Thomson Learning

Heart-Healthy Choices

Copyright 2005 Wadsworth Group, a division of Thomson Learning

Dietary Recommendations
1. Use all fats in moderation
*1 tsp fat = 5 gm = 45 kcals
2. Beware of “hidden fats” – added to
convenience foods, processed foods, & in
cooking
3. Choose lean meats, skinless poultry,
nonfat dairy products; limit meats to <7
oz./day
4. Choose fish 2-3 times/week
5. Choose monounsaturated fats – canola,
olive,
peanut, or sesame oils; avoid hydrogenated
oils
PHOSPHO-
LIPIDS
 Phospholipids are specialized form of
compound lipids containing fatty acids,
glycerol, and phosphorylated nitrogen
bases (serine, ethanolamine, choline,
inositol, sphingosine e.t.c)

The
phosphoric
acid has an
ester
linkage with
alcohol
 Phospholipids structure has 2 distinct
parts: Fat soluble (FAs) and water sol-
uble (phosphate + N – compound),
hence they are amphipathic in na-
ture.

 The hydrophobic portion of the mole-

cules are associated with other non
polar constituents of membranes, in-
cluding glycolipids, protein, and
cholesterol.
 STRUCTURE OF PHOSPHOLIPIDS

 There are two classes of phospholipids: those

that have glycerol (from glucose) as a back-
bone and those that have sphingosine (from
serine and palmitate).
A. Phosphoglycerides- Phospholipids that con-
tain glycerol are called phosphoglycerides (or
glycerophospholipids). Phosphoglycerides con-
stitute the major class of phospholipids and are
the predominant lipids in membranes. All con-
tain (or are derivatives of) phosphatidic acid
(PA), which is diacylglycerol (DAG) with a
phosphate group on carbon 3. PA is the sim-
plest phosphoglyceride and is the precursor of
 STRUCTURE OF PHOSPHOLIPIDS

1. Phospholipids
From Phospha-
tidic Acid And
Alcohol: The
phosphate group
on PA can be es-
terified to an-
other compound
containing an
alcohol group.
 STRUCTURE OF PHOSPHOLIPIDS
2. Cardiolipin: Two molecules of PA esterified
through their phosphate groups to an addi-
tional molecule of glycerol is called cardi-
olipin. Note that cardiolipin is an important
component of the inner mitochondrial mem-
brane and bacterial membrane.

3. Plasmalogens: When the fatty acid at car-

bon 1 of a glycerophospholipid is replaced by
an unsaturated alkyl group attached by an
ether (rather than by an ester) linkage to the
core glycerol molecule, an ether phospho-
glyceride known as a plasmalogen is pro-
duced.
 STRUCTURE OF PHOSPHOLIPIDS
B. Sphingomyelin- The backbone of sphingomyelin
is the amino alcohol sphingosine, rather than
glycerol. [Note: The fatty acids found most fre-
quently in sphingomyelin are palmitic, stearic, lig-
noceric and nervonic acid. The alcohol group at
carbon 1 of sphingosine is esterified to phospho-
rylcholine, producing sphingomyelin, an important
constituent of the myelin sheaths of nerve fibers.
[Note: The myelin sheath is a layered, membra-
nous structure that insulates and protects neu-
ronal fibers of the central nervous system.]
 Phospholipids are divided into three
groups:

1. Phosphoglycerides

2. Phosphoinositides

3. Phosphosphingosides
 Phosphoglycerides
 Major phospholipids in cell membrane
containing two FAs esterified to the 1st & 2nd
OH groups of the glycerol

 The 3rd OH group forms ester bond with

phosphate

 There are 3 subtypes of phosphoglycerides:

Lecithins (phosphotidyl choline), cephalins &
Plasmalogens.
Lecithin for example, is richly abundant in
glandular
and nervous tissues
Chemistry of lecithin; a typical example of phos-
phoglyceride
 Clinical relevance of lecithin
 Lecithin is a com-
ponent of surfactants
produced by type II
alveolar cells.

Partial hydrolysis by
lecithinases (active en-
zyme in snake venoms)
causes removal of one
fatty acid to yield
lysolecithin, which is
responsible for
hemolysis.
 Cephalins

 Cephalins are structurally related to

lecithins
 except that choline is replaced by either
serine
 or ethanolamine.

 It is richly abundant in Soya bean Oil

Venoms containing lecithinases also split

off
one fatty acid from Cephalins thereby
inducing
 Plasmalogens

 Plasmalogens are structurally related to

lecithins and cephalins, except that one
of the
FAs is replaced by an unsaturated alkyl
ether
(O – CH)

 It constitute about 10% of the PLPs in of

brain
and muscle, and it is not found in plant
tissues
 occur in brain tissue
 Available in soybeans
 Very important in transport processes in
cells
 Base is replaced by inositol
o Found in nerve tissue esp. in the my-
elin sheath (hence the name, sphin-
gomyelins)
o Absent in plants and microorganisms.
o Differ from other phospholipids by lack
of glycerol and the presence of another
nitrogenous base sphingosine in place
of glycerol
o deficiency of the enzyme sphingomy-
elinase Niemann−Pick’s disease,
sphingomyelins are stored in the brain
 Overview of Glycolipids
 Glycolipids are molecules that contain both car-
bohydrate and lipid components. Like the phos-
pholipid sphingomyelin, glycolipids are deriva-
tives of ceramides in which a long-chain fatty
acid is attached to the amino alcohol sphingo-
sine. They are, therefore, more precisely called
glycosphingolipids. Like the phospholipids, gly-
cosphingolipids are essential components of all
membranes in the body, but they are found in
greatest amounts in nerve tissue. They are lo-
cated in the outer leaflet of the plasma mem-
brane, where they interact with the extracellular
environment. As such, they play a role in the
regulation of cellular interactions (for example,
 Structure of glycosphingolipids
 The glycosphingolipids differ from sphingomyelin in
that they do not contain phosphate, and the polar
head function is provided by a monosaccharide or
oligosaccharide attached directly to the ceramide by
an O-glycosidic bond.
A. Neutral glycosphingolipids: The simplest neutral
(uncharged) glycosphingolipids are the cerebrosides.
These are ceramide monosaccharides that contain
either a molecule of galactose (forming ceramide-
galactose or galactocerebroside, the most common
cerebroside found in myelin or glucose. [Note: Mem-
bers of a group of galacto- or glucocerebrosides may
also differ from each other in the type of fatty acid
attached to the sphingosine.] As their name implies,
cerebrosides are found predominantly in the brain
 Cerebrosides and gangliosides
I. Cerebrosides
o Important constituent of brain (about 8%)
o consist of one or more sugar units
o are often called glycosphingosides.
o Both phospholipids and glycolipids form self-
sealing lipid bilayers that are the basis for all
cellular membranes
o Deficiency of glucocerebrosidase  cerebros-
ides accumulation in the liver and the spleen in
Gaucher’s disease patient
o Types: kerasin, cerebron, nervon, oxynervon
fatty acid, sphingosine and galactose/glucose in-
stead of choline, but no phosphoric acid.
2. Ganglioside
o A type of glycolipid from brain tissue called
ganglioside
o Found in ganglion cells of nervous tissue and
also in most parenchymatous tissues like
spleen and RBCs
o Consists of sphingosine, sugar
(oligosaccharide) and one or more sialic acid
(N-acetylneuraminic acid)
o They make up about 6% of the membrane
lipids in the grey matter of the brain.
o Act as receptors for toxic pathogens like
Vibrio cholerae, influenza virus and tetanus
B. Acidic glycosphingolipids: Acidic glycosph-
ingolipids are negatively charged at physiologic
pH. The negative charge is provided by N-
acetylneuraminic acid ([NANA], a sialic acid in
gangliosides, or by sulfate groups in sulfatides.
1. Gangliosides: These are the most complex
glycosphingolipids and are found primarily in
the ganglion cells of the CNS, particularly at
the nerve endings.
2. Sulfatides: These sulfoglycosphingolipids are
sulfated galactocerebrosides that are nega-
tively charged at physiologic pH. Sulfatides are
found predominantly in the brain and kidneys.
 Major classes of phospholipids

1. Phosphatidylcholine (PC) also known as

lecithins-component of pulmonary
surfactant (dipalmitoyl-lecithin), 80% of
extracellular phospholipids

2. Phosphatidylethanolamine (PE): also

cephalins, contain ethanolamine, FAs are
palmitic or stearic on C1 and long chain
unsaturated FAs on C2

3. Phosphatidylserine (PS): carries serine with

similar FAs as PE
 Major classes of phospholipids
4. Phosphatidylinositol (PI): contains inositol and
exclusively stearic at C1 and arachidonic acid
at C2

5. Phosphatidylglycerol (PG):
glycerophospholipids, found in surfactants,
also precursor for cardiolipin an important
component of inner mitochondrial membrane
thus the high concentration of PG in the
mitochondrial membrane

6. Diphosphatidylglycerol (DPG): highly acidic,

found in inner mitochondrial membrane and
 Biomedical importance of phospholipids
1. Serving as memrane barrier and allowing
the cell membrane to be fluidy
2. Regulation of cellular respiration via ETC by
cephalin and cardiolipin
3. Help in absorption of fats from the intestine
4. Essential for the synthesis of lipoproteins
thus participate in lipid transport
5. Eicosanoids (prostaglandins, prostacyclins,
thromboxanes) are synthesized from them
via arachidonic acid.
6. Act as surfactants e.g. dipalmitoyl
phosphatidylcholine. Deficiency 
respiratory distress syndrome (RDS)
7. Are used to synthesize second messengers
e.g. PIP2, IP3 and DAG

8. Cephalins participate in blood clotting. PE and

PS increase thrombin formation by promoting
binding to fatctor V and X. 1-alkenyl2-
acetylglycerol-3-phosphocholine a
plasmalogen causes platelet aggregation
called platelet activation factor (PAF)

9. Are used to prepare nanoliposome, ethosomes

and other nano formulations for oral, dermal,
lingual and ocular drug delivery

10. In food technology, they are used as

 phospholipids
 Insufficient amount of pulmonary
surfactant (dipalmitoyl lecithin)
especially in premature babies cause
RDS or hyaline membrane disease
 Fetal lung maturity determined by L/S ratio,
<2.0 indicates potential risk of RDS
 Sphingomyelinase deficiency 
Niemann-Pick disease, an AR disorder.

 Types: A, B, C1, C2 and D.

 All types are associated with mental
retardation, hepatosplenomegaly & early
 Diseases associated with non-phospholipid
sphingolipids
Disorder Enzyme Defi- Accumulating Sub- Symptoms
ciency stance

Hexosaminidase infantile form: rapidly progressing

Tay-Sachs disease GM2 ganglioside mental retardation, blindness,
A (HexA) early mortality

Tay-Sachs AB variant GM2 activator infantile form: same symptoms as

GM2 activator deficiency GM2 ganglioside
(GM2A) Tay-Sachs

Sandhoff-Jatzkewitz globoside; GM2gan- infantile form: same symptoms as

disease HexA and HexB Tay-Sachs, progresses more
glioside rapidly

acid β-glucosi- hepatosplenomegaly, mental re-

Gaucher disease dase glucocerebrosides tardation in infantile form, long
(glucocerebrosi- bone degeneration
dase)

globotriaosylce-
Fabry disease α-galactosidase ramide; also called ce- kidney failure, skin rashes
A ramide trihexoside
(CTH)
 Accumulating Sub-
Disorder Enzyme Deficiency Symptoms
stance

Krabbes disease
mental retardation,
globoid cell leukodys- galactocerebrosidase galactocerebrosides
myelin deficiency
trophy (GLD)

mental retardation,
GM1gangliosidosis β-galactosidase-1 GM1 gangliosides skeletal abnormalities,
hepatomegaly

Metachromatic mental retardation,

leukodystrophy arylsulfatase A sulfatides metachromasia of
sulfatide lipodosis nerves

cerebral degeneration,
pentahexosylfuco-
Fucosidosis α-fucosidase thickened skin, muscle
glycolipid
spasticity

Farber lipogranulo- hepatosplenomegaly,

acid ceramidase ceramides
matosis painful swollen joints
STEROLS
Chemistry
of Sterols

Structure
consists of
carbon rings
 STEROLS
 Examples of sterols of clinical importance
are:
1. Sex hormone – testosterone
2. Vitamin D
3. Bile (aids fat digestion)
4. Adrenal hormones - cortisol
5. Cholesterol – made by the liver
and supplied in foods such as egg
yolk, liver, meat & dairy products
 CHOLESTEROL
 Cholesterol is a sterol forming important structural
component of cell membrane

 It consists of 4 fused A-D rings called

steroid nucleus
 It has an OH group at C3

 It has an 8-carbon chain attached to C17

 It has a double bond between C5 and C6

 STRUCTURE

22 24
. 26

18 20 23
CH
,
27
1 ]6
19
L C D
C 14
l
15
H,
10
A B
5 7
·-...

OH
6
 Sources of Cholesterol
Cholesterol has endogenous and
exogenous sources.
 >50% of cholesterol is synthesised de novo
in almost all nucleated cells mainly in the liver.

 Adrenal cortex, gonads, skin, and intestine

also actively synthesize cholesterol

Exogenous cholesterol mainly comes from diet

Dietary source of Cholesterol

Copyright 2005 Wadsworth Group, a division of Thomson Learning

 Functions of Cholesterol

 Important component of cell mem-

brane structure influencing its fluidity
and permeability

 Serves as a precursor of steroids (i.e.

steroid hormones, bile acids and Vita-
min D)
[ .UMMAR} O IpOpROTEINS COMpOSITIONS
Lipoprotein Density Diameter Protein Phos- Triacyl Apoproteins
class (g/mL) (nm) % lipids % glycero
pho
Is %

1.063-1.21 5- 15 33 29 A,
C(I,II,III),
D, E
1.019 - 18 - 28 25 B100
1.

30 - 80 10 B100,
C(I,II,I
E