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 solvents (benzene,
chloroform, ethanol, ether,
CCL4, acetone, etc)

 Lipids consist of alcohol and

fatty acids joined together by
ester linkage
 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 sheath

4. Protect internal organs by cushioning effect

5. Provide shape and contour to the body

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

9. Protects against changes due to external heat e.g.

10. subcutaneous fat

10. Helps in the absorption of fat soluble vitamins

 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 diseases
 CLASSIFICATION OF LIPIDS

Phospholipids, glycolipids steroids,

TGs & (cerebroside, globoside, cholesterol,
waxes ganglioside), sulpholipids PGs,
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)

TRIGLYCERIDES
 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

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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, butyric
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 metabolic
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 COOH

or ω1, ω2, ω3…. Starting from CH3 group
 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 during
metabolism trans isomers may be formed
 They could be MUFA or PUFA
 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 carbon 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 starting 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 stable fats in
food industries that resists oxidation 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 Butter & Margarine 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
6. Limit egg yolks to 3-4/week
PHOSPHOLIPIDS
 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 soluble (phosphate
+ N – compound), hence they are amphipathic
in nature.

 The hydrophobic portion of the molecules are

associated with other non polar constituents
of membranes, including glycolipids, protein,
and cholesterol.
 STRUCTURE OF PHOSPHOLIPIDS

 There are two classes of phospholipids: those that have

glycerol (from glucose) as a backbone and those that have
sphingosine (from serine and palmitate).
A. Phosphoglycerides- Phospholipids that contain glycerol
are called phosphoglycerides (or glycerophospholipids).
Phosphoglycerides constitute the major class of
phospholipids and are the predominant lipids in
membranes. All contain (or are derivatives of)
phosphatidic acid (PA), which is diacylglycerol (DAG) with
a phosphate group on carbon 3. PA is the simplest
phosphoglyceride and is the precursor of the other
members of this group.
 STRUCTURE OF PHOSPHOLIPIDS

1. Phospholipids From
Phosphatidic Acid
And Alcohol: The
phosphate group on
PA can be esterified
to another
compound
containing an
alcohol group.
 STRUCTURE OF PHOSPHOLIPIDS
2. Cardiolipin: Two molecules of PA esterified through
their phosphate groups to an additional molecule of
glycerol is called cardiolipin. Note that cardiolipin is an
important component of the inner mitochondrial
membrane and bacterial membrane.

3. Plasmalogens: When the fatty acid at carbon 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
phosphoglyceride known as a plasmalogen is produced.
 STRUCTURE OF PHOSPHOLIPIDS
B. Sphingomyelin- The backbone of sphingomyelin is the
amino alcohol sphingosine, rather than glycerol. [Note:
The fatty acids found most frequently in
sphingomyelin are palmitic, stearic, lignoceric and
nervonic acid. The alcohol group at carbon 1 of
sphingosine is esterified to phosphorylcholine,
producing sphingomyelin, an important constituent of
the myelin sheaths of nerve fibers. [Note: The myelin
sheath is a layered, membranous structure that
insulates and protects neuronal 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 phosphoglyceride
 Clinical relevance of lecithin

 Lecithin is a component
of surfactants produced by
type II alveolar cells.

Partial hydrolysis by
lecithinases (active enzyme
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
hemolysis.
 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

Nitrogen base could be serine, ethanolamine

or choline
 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 myelin sheath
(hence the name, sphingomyelins)
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 sphingomyelinase
Niemann−Pick’s disease, sphingomyelins are
stored in the brain in large quantities.
o .
 Overview of Glycolipids
 Glycolipids are molecules that contain both carbohydrate
and lipid components. Like the phospholipid sphingomyelin,
glycolipids are derivatives of ceramides in which a long-
chain fatty acid is attached to the amino alcohol sphingosine.
They are, therefore, more precisely called glycosphingolipids.
Like the phospholipids, glycosphingolipids are essential
components of all membranes in the body, but they are
found in greatest amounts in nerve tissue. They are located
in the outer leaflet of the plasma membrane, where they
interact with the extracellular environment. As such, they
play a role in the regulation of cellular interactions (for
example, adhesion and recognition), growth, and
development.
 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: Members
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 and peripheral nervous tissue, with high concentrations
in the myelin sheath.
 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  cerebrosides
accumulation in the liver and the spleen in Gaucher’s
disease patient
o Types: kerasin, cerebron, nervon, oxynervon
fatty acid, sphingosine and galactose/glucose instead 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 toxin.
o They are also suggested to play a role in cell-cell
interaction
B. Acidic glycosphingolipids: Acidic
glycosphingolipids 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 negatively
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 also component of
surfactants. Cardiolipin is an imp e.g.
 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

7. In food technology, they are used as emulsifiers to allow

oils form colloids with water
 Clinical significance of 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 mortality
 Diseases associated with non-phospholipid sphingolipids
Enzyme Accumulating
Disorder Symptoms
Deficiency Substance

infantile form: rapidly

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

Tay-Sachs AB variant
GM2 activator infantile form: same symptoms
GM2 activator GM2 ganglioside
(GM2A) as Tay-Sachs
deficiency

globoside; infantile form: same symptoms

Sandhoff-Jatzkewitz
HexA and HexB GM2 ganglioside as Tay-Sachs, progresses more
disease
rapidly

acid β-
hepatosplenomegaly, mental
glucosidase
Gaucher disease glucocerebrosides retardation in infantile form, long
(glucocerebrosid
bone degeneration
ase)
globotriaosylceramid
α-galactosidase e; also called
Fabry disease kidney failure, skin rashes
A ceramide trihexoside
(CTH)
 Accumulating
Disorder Enzyme Deficiency Symptoms
Substance

Krabbes disease
galactocerebroside mental retardation,
globoid cell galactocerebrosidase
s myelin deficiency
leukodystrophy (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,
pentahexosylfucogl
Fucosidosis α-fucosidase thickened skin, muscle
ycolipid
spasticity

Farber hepatosplenomegaly,
acid ceramidase ceramides
lipogranulomatosis 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 membrane

structure influencing its fluidity and
permeability

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

hormones, bile acids and Vitamin D)
[ .UMMAR} O IpOpROTEINS COMpOSITIONS
Lipoprotein Density Diameter Protein Phospho Triacyl Apoproteins
class (g/mL) (nm) % lipids % glycero
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