Nizar Kishkeh , MD
Assistant Professor
Department of Laboratory Medicine
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Lipids
 Are large group of organic molecules, consist of carbon ,
hydrogen, and oxygen, but unlike carbohydrates, they do
not have a 2:1 ratio of hydrogen to oxygen .
 Some lipids contain phosphorus and nitrogen
 Are insoluble in water ( hydrophobic) , but soluble in
organic solvents such as alcohol
 Include :
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Fatty acids
Triglycerides (TGs)
Cholesterol
Phospholipids
Glycolipids
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Classification of Fatty Acids
I-The Length of the Carbon Chain:
Short-chain, medium-chain, Long-chain.
II-The Degree of saturation:
Saturated, unsaturated(monounsaturated,
polyunsaturated).
III-The Location of Double Bonds:
Omega-3 fatty acid, omega-6 fatty acid
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Fatty acids (R-COOH)
 Can be classified depending on their length into :
 Short- chain (4-6 carbon atoms ) fatty acids :
e.g. butyric acid(c4)
 Medium- chain (6-12 carbon atoms ) fatty acids:
e.g.Caproic acid (C6),Capric acid (C10),Lauric acid(c12).
 Long- chain (> 12 carbon atoms ) fatty acids :
e.g. palmitic(C16), stearic(C18),oleic(C18),
linoleic(C18),Alpha-linolenic(C18 and arachidonic
(C20) acids
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Fatty acids (R-COOH)
 Can be classified depending on degree of saturation to :
 Saturated fatty acids :
contain only single bonds , e.g. palmitic, butyric and
stearic acids
 Unsaturated fatty acids :
contain one double bond or more between some carbon
atoms :
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Monounsaturated (MUFA) , such as oleic acid .
Polyunsaturated ( PUFA) , such as linoleic(2 double bonds)
and linolenic (3 double bonds), and arachidonic (4 double
bonds) acids
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Saturated and unsaturated Fatty acids
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Fatty acids
 In plasma :
 The majority of FA are found in TG or phospholipids
 A small amount exists in free unesterified form , most of
which is bound to albumin
 Can be used as fuel.
 May be used in re-synthesis of other molecules.
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Essential Fatty Acids
 Are essential to human health , but can’t be made by human
body and must be obtained from foods or supplements
 Include:
 Linoleic acid, which is the precursor of arachidonic acid, the
substrate for prostaglandin synthesis
 α-linolenic acid, which is the precursor of other ω-3 fatty
acids important for growth and development. Note:
Arachidonic acid becomes essential if linoleic acid is deficient
in the diet.
 Functions:
 Are essential for formation of healthy cell membrane.
 Are essential for development and function of brain.
 Regulation of blood viscosity ,inflammatory ,and immune responses
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Omega-3 fatty acids
 Are a family of essential fatty acids contain two double bonds
or more, one of these double bonds is 3 carbon atoms from
the terminal methyl group
 Are present mainly in oily fish
 Include :
 Linolenic acid.
 Ecosapentanoic acid (EPA).
 Docosahexanoic acid (DHA).
 Have the following benefits:
 Protective effect against heart disease and stroke by lowering LDL-c
and raising HDL-c
 Anti-thrombotic and vasodilatory properties
 Anti-inflammatory properties
 They decrease bone loss
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TRIACYLGLYCEROLS (TAGs)
 Are the most plentiful lipids in our body and diet
 Consist of molecule of glycerol and 3 fatty acid molecules
attached to it by ester bonds.
 Most TAGs from plant sources ( corn, sunflower , safflower
seeds ,soybean) and fatty fish
(salmon ,tuna...) are rich in polyunsaturated fatty acids and
are oils at room temperature.
 TG from animal sources ( meats , whole milk ,cheese and
butter) contain mostly saturated fatty acids and are usually
solid at room temperature .
 Are major source of stored energy in the body ,store more
than twice as much chemical energy per gram as
carbohydartes or proteins
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TRIACYLGLYCEROLS
In a triacylglycerol:
 Glycerol forms ester bonds with three fatty acids.
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Triacyglycerol formation
+ Fatty Acids
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TAG Functions
 Energy source:
9 kcals per gram.
 Are major source of stored energy in the body.
 Thermal insulation and protection of internal organs.
 Sources of essential fatty acids
 They are carriers of fat- soluble vitamins.
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Cholesterol
 Free cholesterol :
 Unsaturated steroid alcohol containing 4 rings ( A ,B ,C ,and
D ), and has single C-H side chain tail.
 The only hydrophilic part of it is the hydroxyl group in the Aring .
 Is found on the surface of lipid layers along with
phospholipids.
 In plasma , it constitutes about 30 % of total cholesterol.
 Esterified cholesterol :
 The hydroxyl
group in free cholesterol is conjugated by an
ester bond to a fatty acid, in plasma by LCAT and in cells by
ACAT
 Hydrophopic , so it is not found on the surface of lipid layers
but in center of lipid drops, along with TG.
 In plasma , it constitutes about 70 % of total cholesterol.
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Cholesterol structure
“free” Cholesterol
consists of :
-4 fused hydrocarbon rings
(A, B, C, and D, called the
“steroid nucleus”).
-An eight-carbon, branched
hydrocarbon chain
attached to C-17 of the D
ring.
-Ring A has a hydroxyl
group at C-3.
-Ring B has a double bond
between C-5 and C-6.
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Cholesterol
 Sources of cholesterol :
 Dietary cholesterol.
 De novo biosynthesis, almost exclusively synthesized by
animals.
 Functions of cholesterol :
 Is an essential component of cell membranes .
 Is a precursor for :
Primary bile acids (cholic and chenodeoxycholic acids).
 Steroid hormones in adrenal gland, testis, and ovary .
 Vit D3 : from 7- dehydrocholesterol in skin.
 Doese not serve as a source of fuel.
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Glycerophospholipids
 Are composed of glycerol backbone with 2
esterified fatty acids and a phosophate group
(PHOSPHATIDIC ACID) attached to an amino
alcohol that may be :
 Choline ----> phosphatidylcholine PC (lecithin )
 Ethanolamine ---> phosphatidylEthanloamine (PE)
(cephalin)
 Serine---> phosphatidylserine(PS)
 Inositol---> phosphatidylInositol(PI)
 Are amphipathic molecules
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Glycerophospholipids
 Are the main class of phospholipids
 They are similar to triacylglycerols, but have one ester bond
replaced with an amino alcohol phosphate ester.
 Glycerophospholipids are the main lipid component of cell
membranes, and are important in the cell’s
semipermeability.
 These abilities of glycerophospholipids are due to their
amphipathic nature, with a polar head group and nonpolar
tails.
Fatty acid
Glycerol
Fatty acid
PO4
Amino
alcohol
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Glycerophospholipids are
amphipathic compounds
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Phospholipids are amphipathic
molecules
 The glycerol and head
group moieties are
hydrophilic - readily
associate with water
 The fatty acyl part of
the molecule is
hydrophobic .
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Glycerophospholipids
 Can be classifiedbased on the amino alchol group
 Two common types are:
 lecithin (which contains choline)
 cephalins (which contain ethanolamine)
 Lecithins and cephalins are highly abundant in brain and
nerve tissues, and are also found in egg yolks, wheat germ
.and yeast
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Cardiolipin
• Is a kind of diphosphatidylglycero lipid:
• Two phosphatidylglycerols connect with a glycerol backbone in the center
to form a dimeric structure.
• Since there are two phosphates in the molecule, each of them can catch one
proton.
• Under normal physiological conditions (wherein pH is around 7), the
molecule may carry only one negative charge.
• Cardiolipin is an important component of the inner mitochondrial
membrane, where it constitutes about 20% of the total lipid composition.
can also be found is in the membranes of most bacteria.
• The name ‘cardiolipin’ is derived from the fact that it was first found in
animal hearts. It was first isolated from beef heart in the early 1940s.
Functions:
It is essential for the optimal function of numerous enzymes of inner
mitochondrial membrane that are involved in mitochondrial energy
metabolism.
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Cardiolipin structure
Cardiolipin(diphosphatidylglycerol):
• consists of two molecules of
Phosphatidic acid esterified through
their phosphate groups to an additional
molecule of glycerol .
• Cardiolipin is found in bacteria and
eukaryotes.
• In eukaryotes, cardiolipin is virtually
exclusive to the inner mitochondrial
membrane, where it appears to be
required for the maintenance of certain
respiratory complexes.
• Cardiolipin is antigenic, and is
recognized by antibodies raised against
Treponema pallidum, the bacterium that
causes syphilis.
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Cardiolipin structure
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Ether Phospholipids
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Plasmalogens
• Are a type of ether phospholipid characterized by the
presence of a vinyl ether linkage at the sn-1 position and an
ester linkage at the sn-2 position.
• In mammals, the sn-1 position is typically derived from
C16:0, C18:0, or C18:1 fatty alcohols while the sn-2 position
is most commonly occupied by polyunsaturated fatty acids
(PUFAs).
• The most common head groups present in mammalian
plasmalogens are :
• Ethanolamine (plasmenylethalomines)
• Choline (plasmenylcholines)
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General structure of a plasmalogen
General structure
of a plasmalogen:
• Carbon 1 of glycerol is
joined to a long-chain fatty
alcohol by an ether linkage.
• The fatty alcohol group
has a double bond between
carbons1 and 2.
• The head group is usually
ethanolamine or choline.
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Plasmalogens
Main Functions:
• Plasmalogens are found in numerous human tissues
particlurly in the nervous, immune, and cardiovascular
system.
• In human heart tissue, nearly 30-40% of choline
glycerophospholipids are plasmalogens,
• Almost 30% of the glycerophospholipids in the adult human
brain and up to 70% of myelin sheath ethanolamine
glycerophospholipids are plasmalogens.
• They can protect mammalian cells against the damaging
effects of Reactive oxygen species.
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Structure of Platelet Activating Factor (PAF)
Platelet-activating factor (PAF):
• Is an unusual ether
glycerophospholipid, with a
saturated alkyl group in an ether
link to carbon 1 and an acetyl
residue (rather than a fatty acid)
at carbon 2 of the glycerol
backbone .
• Is synthesized and released by
a variety of cell types.
• It activates inflammatory cells
and mediates hypersensitivity,
acute inflammatory, and
anaphylactic reactions.
• It causes platelets to
aggregate and degranulate, and
neutrophils and alveolar
macrophages to generate
superoxide radicals.
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Sphingophospholipids
 Are phospholipids that are based on the 18-carbon
amino alchol sphingosine, instead of on glycerol.
 A fatty acid is linked to the amine group by an
amide bond, and an amino alcohol phosphate ester
is linked to the bottom hydroxyl group (the top
hydroxyl group remains free).
 Sphingolipids are also abundant in cell
membranes, particularly in brain and nerve tissues
 Sphingmyelin, is the main component of the
myelin sheath of nerve cells.
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Sphingomyelin:
-It consists of ceramide
(sphingosine+one fatty acid ) and
phosphate group attached to choline
-Is prevalent in myelin sheath of nerve
fibers
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Sphingomyelin
• Sphingomyelin cocnsists of :
• Sphingosine (an amino
alcohol ).
• A long-chain fatty acid is
attached to the amino group
of sphingosine through an
amide linkage, producing a
ceramide.
• phosphorylcholine
esterified to the alcohol group
at carbon 1 of sphingosine .
• Sphingomyelin is an important
constituent of the myelin of
nerve fibers.
• The myelin sheath is a layered,
membranous structure that
insulates and protects neuronal
fibers of the central nervous
system.
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Sphingomyelin structure
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Glycolipids
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 Consists of ceramid and one sugar residue or more , and
can be classified into :
1-Cerebrosides =glucosyl or galactosyl ceramid
2-Globosides =ceramid + two sugar residues or more
3-Gangliosides = ceramid + sugar residues + NANA
(N-Acetyl Neuraminic Acid )
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Cerebrosides
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Gangliosides
 Gangliosides are acidic glycosphingolipids
 They contain oligosaccharides with terminal, charged N-
acetyl neuraminic acids (NANA)
 Depending on the number of NANA sugars, gangliosides
are designated M, D, T, Q (e.g., GM).
 Accumulation of the ganglioside GM2 causes Tay-Sachs.
Ganglioside GM2
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Ganglioside structure
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Catabolism of sphingolipids in
humans
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Lipid storage diseases
 Are a group of inherited metabolic disorders usually, due to
lack of an enzyme leads to accumulation of a particular
lipid.
 Over time, this excessive storage of lipids can cause
permanent cellular and tissue damage, particularly in the
brain,peripheral nervous, liver, spleen, and bone marrow.
 Symptoms may appear early in life or develop in the teen or
even adult years such as :
 Enlarged spleen and liver
 Seizures
 Blindness
 Mental retardation and learning problems.
 Death
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Sphingomyelin degradation
 Sphingomyelin is degraded
in lysosomes by
sphingomyelinase to give
ceramide,
 and ceramidase to give
sphingosine
 Niemann-Pick disease is
due to sphingomyelinase
deficiency
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