CHEMISTRY OF LIPIDS- COMPOUND

LIPIDS

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WHAT REMAINS TO BE COVERED IN THE
CHAPTER

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 SPECIFIC LEARNING OBJECTIVES
By the end of this class we must be able to...
1. Define and classify Phospholipids with examples,
importance, and functions
2. Describe the role of dipalmitoyl phosphatidyl
choline in pulmonary surfactant

3. Describe the action of phospholipases

4. List the components and examples of glycolipids
5. Name the lipoproteins and their functions.
6. Name the Sterols and their structure

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 Lipids
Compound
1. Phospholipids
Miscellaneous
Simple (Glycerophospholipids Derived
–PC, PE, PS, PA, PI, C,
1. Fats/oils- Fatty acids,
Plsmlgn, &
TriAcylGlyc glycerol,
Sphingophospholipids-
erol (TAG)- cholesterol &
Sphingomyelin) Hydrocarbons,
tristearin, other Fatty
2. Glycolipids Terpenes,
tripalmitin alcohols, fat
(Cerebrosides, Carotenoids, fat
2. Waxes- soluble vitamins
gangliosides etc) soluble vitamins
Cerumen, A & D, ketone
3. Lipoproteins (CM, E&K
Sebum bodies, bile
VLDL, LDL, HDL, FFA)
Bees wax, acids,
4. Sulpholipids- sulfated
Cholesterol prostaglandins,
ganglioside , sulf
ester, hormones
globoside, sulf
Retinol
cerebroside
ester
5. Aminolipids &
Lipopolysaccharides
 Glycerophospholipids
Phospholipids
Sphingophospholipids
Compound Lipids
(Alc+FA+P+Nitro base)
Amphipathic Ester link

Stereo chemical/specific
numbering- sn-1, sn-2, sn-3

Amide link 5
SPHINGOPHOSPHOLIPID

GLYCEROPHOSPHOLIPID
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Glycerophopsholipids
Usually one saturated and one
unsaturated FA
Ex-Palmitic, Stearic, Oleic,
Linoleic, Arachidonic acid

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 Types of glycerophopholipids
1. Phosphatidic acid
2. Lecithin/Phosphatidyl
Choline
3. Cephalin/ Phosphatidyl
ethanolamine
4. Phosphatidyl inositol
5. Phosphatidylserine
6. Plasmalogens
7. Cardiolipin

Nitrogen-Containing glycero-
Phospholipids
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Phosphatidic acid
 Simplest phospholipid- no N2
base
 Structure
 Intermediate in the synthesis of
TAG and other Phospholipids

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 Lecithin/Phosphatidyl Choline
 Most abundant PL in membranes
 Phosphatidic acid with the quaternary
N base choline
 Constituent of bile- for lipid digestion
 Store for choline in body. ? Functions
 Choline- ACh synthesis, methyl group
donor(methionine metabolism),
lipoprotein formation, cell signalling
 Dipalmitoyl lecithin- lung surfactant

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 Lungstracheabronchibronchiolesalveoli
 Each alveolus has a thin fluid coating to facilitate gas
transfer between air and blood
 Type II alveolar cells secrete surfactant that lines the
air-water interface
 Surfactant is composed of Dipalmitoyl lecithin, other
phospholipids(lecithin, phosphatidyl inositol, phosphatidyl
ethanolamine, sphingomyelin), cholesterol, Proteins-
albumin, Immunoglobulins, Surfactant
Proteins(immunity) A, B, C, D 12
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• Surfactant- adsorbing to the air-water interface of alveoli, with
hydrophilic head groups in the water and the hydrophobic tails
facing towards the air.
• Reduces surface tension at the fluid air interface.
• Lowers the work of breathing and prevents collapse of alveoli/
lung at the end of expiration
• Synthesis of surfactant starts at 26 weeks in-utero , continues
till 35 weeks Mature fetal lungs
• Absence of surfactant leads to Respiratory Distress Syndrome
(RDS) in premature infants born 28-32 weeks
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 RDS- hypoxia, fast breathing (>60
breaths per minute), a fast heart rate,
chest wall retractions expiratory
grunting, nasal flaring and blue
discoloration of the skin during
breathing efforts- respiratory failure.
 Fetal lung maturity has to be evaluated
before planning a premature delivery
 Assessment of fetal lung maturity -
amniocentesis- lecithin-sphingomyelin
ratio ("L/S ratio")(<2:1- immaturity) and
the surfactant/albumin (S/A) ratio
(<35mg surfactant protein per g of
albumin- immature lungs)
 Maternal steroids promote fetal lung
maturity prior to delivery 15
Cephalins/phosphatidyl ethanolamine

1.Found in bio-membranes
like lecithin
2.Constituent of
Thromboplastin- converts
prothrombin to thrombin-
Involved in blood clotting
3.Increases Lipoprotein
secretion from liver

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 Phosphatidyl-inositol
 Phosphatidic acid with
inositol (Sugar alcohol
derived from Glucose 6
PO4 in the body )
 Cell membranes cytosolic
aspect- cell signalling and
membrane trafficking
 PI derivatives- DAG & IP3–
act as 2nd messengers and
Mediate action of certain
peptide hormones- Epi
(α1 receptor), oxytocin,
ADH(V1 receptor)
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 Phosphatidyl-serine

 Found in cell membranes-

inner leaflet
 Plays a key role in cell
signalling & apoptosis-
programmed cell death.
 Damaged/defective cell
apoptosisPS moves to
outer leaflet-signal for
macrophages to
phagocytose dead cells
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 Plasmalogens
 sn-1 of glycerol is attached in an ether linkage (–
O–CH=CH–) and not an ester linkage(-O-C=O) to
unsaturated fatty acid
 The N base can be choline, serine, ethanolamine
or rarely inositol

 Example is platelet-activating factor (PAF), a

choline plasmalogen secreted by (host defence
cells) platelets, endothelial cells, neutrophils,
monocytes, and macrophages.

 PAF mediates many leukocyte functions, platelet

aggregation, WBC degranulation, inflammation,
and anaphylaxis

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CARDIOLIPIN

G G
FA-1 G FA-3
L L
L
Y Y
FA-2 Y
C FA-4 C
C
E E
E
R R
P R
O P O
O
L L
L

• Two molecules of phosphatidic acid linked by a

molecule of glycerol through phosphate groups
• Inner mitochondrial membrane of animal and
plant cells & in bacterial cell walls

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 Cardiolipin
 Isolated first from cardiac muscle
 2 molecules of phosphatidic acid
held by glycerol
 Found in the inner mitochondrial
membrane (cellular respiration and
ATP formation)
 Only phospholipid that has antigenic
properties- anticardiolipin
antibodies (Antiphospholipid
syndrome, Systemic lupus
erythromatosus SLE )
 Low cardiolipin levels can lead to
mitochondrial dysfunction - aging
and myopathy 21
 Fatty acid 18-24
Sphingophospholipids C atoms long
PUFA

SPHINGOMYELIN

Brain, nerves &

in ↓amt. In lungs,
blood, liver etc
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 Recap- Types of phopholipids
1. Phosphatidic acid -intermediate in synthesis of TG, PL
2. Lecithin/Phosphatidyl Choline – membranes, Bile,
choline store, surfactant
3. Cephalin/ Phosphatidyl ethanolamine- membranes,
blood clotting and secretion of Lipoproteins from liver
4. Phosphatidyl inositol- membranes, cell signalling,
membrane trafficking
5. Phosphatidylserine- membranes, apoptosis
6. Plasmalogens- protects against free radicals, PAF-
allergy, inflammation, platelet aggregation
7. Cardiolipin- inner mitochondrial membrane,
dysfunction in aging & myopathy
8. Sphingomyelin: myelin sheath and brain

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Functions of phospholipids
1. Structural components of biological membranes-
regulate permeability.
2. Structural components (lecithin, cephalin,
cardiolipin) of mitochondrial membrane- required
for energy generation and functioning of
mitochondria.
3. PL are amphipathic in nature and are required to be
present in bile for digestion & absorption of dietary
fat from intestine
4. Required for Lipoprotein synthesis and transport of
lipids and PL act as Lipotropic factors- prevent fatty
liver by transporting lipids from liver to tissues
5. Arachidonic acid- released from membrane
Phospholipid hydrolysis is a precursor for
Prostaglandin synthesis. 24
 Functions of phospholipids
6.Act as lung surfactants-Dipalmitoyl phosphatidyl
choline- preventing Respiratory Distress
Syndrome
7.Cephalins- required for blood clotting mechanism
8 Phosphatidyl serine-inner leaflet of the cell
membrane (cell signaling, apoptosis)
9.Membrane PL(P-inositol and its phosphate
derivatives IP3 & DAG) involved in signal
transmission across the membrane (action of
hormones)- cell signalling and membrane
trafficking. PAF- allergy, inflmtn, pltlet aggrg.
10. Sphingomyelins- in myelin sheath that surrounds
nerve fibers (transmission of nerve impulses)
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 Functions of phospholipids

Components of cell membrane, regulate

permeability, mitochondrial membrane
integrity, signal transduction
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Functions of phospholipids

Lipid digestion and absorption,

lipid transport, lipotropic factors,
reverse cholesterol transport

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 Eicosanoid synthesis,
sphingomyelin- nerve
conduction.
Surfactants- RDS, Cephalins-
Blood clotting

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 Lipids
Compound
1. Phospholipids
Miscellaneous
Simple (Glycerophospholipids Derived
–PC, PE, PS, PA, PI, C,
1. Fats/oils- Fatty acids,
Plsmlgn, &
TriAcylGlyc glycerol,
Sphingophospholipids-
erol (TAG)- cholesterol &
Sphingomyelin) Hydrocarbons,
tristearin, other Fatty
2. Glycolipids Terpenes,
tripalmitin alcohols, fat
(Cerebrosides, Carotenoids, fat
2. Waxes- soluble vitamins
gangliosides etc) soluble vitamins
Cerumen, A & D, ketone
3. Lipoproteins (CM, E&K
Sebum bodies, bile
VLDL, LDL, HDL, FFA)
Bees wax, acids,
4. Sulpholipids- sulfated
Cholesterol prostaglandins,
ganglioside , sulf
ester, hormones
globoside, sulf
Retinol
cerebroside
ester
5. Aminolipids &
Lipopolysaccharides
 Glycolipids/ Glycosphingolipids
 Constituents of outer leaflet of
cell membranes and nervous
tissues
 Cell-cell recognition,
communication, receptors for
hormones, toxins
 Examples are cerebrosides
(simplest), globoside and
gangliosides (most complex)

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Glycolipids-Cerebrosides & Globosides

Cerebroside: Ceramide (Sphingosine with fatty acid) + one sugar

(Glucose or Galactose)  gluco cerebroside or galacto cerebroside

Globoside: Ceramide (Sphingosine with fatty acid) + 2 sugars

(Glucose & or Galactose)  Lactosylceramide (ceramide-Gal-Glu)
in RBC membrane

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Glycolipids-Gangliosides
 Gangliosides are found in the ganglion of
nerves

 Ceramide linked through a glycosidic bond

with an oligosaccharide chain

 Oligosaccharide chain contains hexose,

amino sugars and one or more neuraminic
acids(sugar derivatives)

 Ex: GM3, GM1

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Lipoproteins
 Spherical Molecular complexes
consisting of lipids and proteins
 Compound Lipids- Transport vehicles
for lipids in blood
 Neutral lipid core (TAG & Cholesteryl
ester)
 Peripheral coat of PL, proteins
(apoproteins) and free cholesterol
 Polar portions exposed on the outer
surface of the lipoprotein

1. Chylomicrons
2. VLDL
3. IDL
4. LDL
5. HDL
6. Free Fatty Acids
Classification & Functions of Lipoproteins

1.Chylomicrons- transport dietary lipids to peripheral tissues & liver

from intestine.

2.Very Low Density Lipoproteins (VLDL)- transports endogenously

synthesized TAG from liver to peripheral tissues

3.Low Density Lipoproteins (LDL- bad cholesterol) –Transports

Cholesterol from liver to peripheral tissues

4.High Density Lipoproteins (HDL-good cholesterol) – Transports

cholesterol from peripheral tissues to liver for excretion in bile-
REVERSE CHOLESTEROL TRANSPORT
5.Free Fatty Acids (FFA) – present in blood transported by albumin to
the liver for oxidation to release energy

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 Lipids
Compound
1. Phospholipids
Miscellaneous
Simple (Glycerophospholipids Derived
–PC, PE, PS, PA, PI, C,
1. Fats/oils- Fatty acids,
Plsmlgn, &
TriAcylGlyc glycerol,
Sphingophospholipids-
erol (TAG)- cholesterol &
Sphingomyelin) Hydrocarbons,
tristearin, other Fatty
2. Glycolipids Terpenes,
tripalmitin alcohols, fat
(Cerebrosides, Carotenoids, fat
2. Waxes- soluble vitamins
gangliosides etc) soluble vitamins
Cerumen, A & D, ketone
3. Lipoproteins (CM, E&K
Sebum bodies, bile
VLDL, LDL, HDL, FFA)
Bees wax, acids,
4. Sulpholipids- sulfated
Cholesterol prostaglandins,
ganglioside , sulf
ester, hormones
globoside, sulf
Retinol
cerebroside
ester
5. Aminolipids &
Lipopolysaccharides
Steroids/ Sterols (-OH group)
 Derived Lipids- alcohol
with cyclic steroid
nucleus

 CYCLO PENTANO PER

HYDRO
PHENANTHRENE RING

 Found in steroids-
Cholesterol, bile acids,
Vit D, Sex hormones,
adrenocortical hormones
OTHER STEROIDS?

Aldosterone

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 Free Cholesterol  Esterified Cholesterol
 Cell membranes  Stored inside cells
 Derived lipid  Simple Lipid- wax
 Amphipathic  Hydrophobic
 Present in cell membranes-
Maintains membrane
structure, fluidity,
permeability
 Present in myelin sheath -
Insulating cover for
transmission of impulses in
nervous tissue
 Synthesis of bile acids (lipid
digestion and absorption), Vit
D, Sex hormones,
Adrenocortical hormones

Functions of free Cholesterol

Actions of Phospholipases
 Enzymes that hydrolyse PL
 A1, A2, C, D
 Phospholipase A1 - cleaves the SN-1
acyl chain FA + acyl glycero
phosphoryl choline

 Phospholipase A2 - cleaves the SN-2

acyl chainlysolecithin +FA

 Phospholipase C - cleaves before the

phosphate, releasing 1, 2
diacylglycerol and a Phosphoryl
choline. Found in hepatic lysosomes.
 Phospholipase D - cleaves after the
phosphate, releasing phosphatidic acid
and a base.
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 Actions of Phospholipases

 Phospolipase A2 acts on intact lecithin molecule and

hydrolyses the fatty acid esterified to the second carbon
atom.
 PLA2 is an enzyme present in human digestive tract & inside
cells-releases Arachidonic acid from C-2 for prostaglandin
synthesis
 The product formed is LYSOLECITHIN and fatty acid
(arachidonic acid). lysolecithin is a hemolytic substance.
 PLA2 is an enzyme present in human digestive tract, the
venom of the viper snakes, scorpions and spiders 42
THANK YOU

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