Lipid chemistry

1. 1
Course contents
1. Define and classify lipids and describe their
biochemical function.
2. Define and classify fatty acids and describe their
biochemical functions.
3. List and describe the function of essential fatty
acids.
4. Describe the structure and biochemical function
of phospholipids glycolipids sphingolipids.

2. 2
5. Discuss Eicosanoides and their
function in health and disease.
6. Describe steroids and their
biochemical role.
7. Define cholesterol and describe its
structure chemistry and function.
8. Discuss lipid peroxidation and its
significance.

3. 3
Definition
Heterogeneous group of
• water insoluble
• organic molecules
• That can be extracted from the tissues
by nonpolar solvents

4. 4
lipids
• Related to each other more by their
physical properties than chemical
nature
• all have diverse chemical structures
and functions
• major common feature is that
all are relatively insoluble in water

5. 5
Biological importance 1
• High energy value
One gm of fat supplies 9.1 Kcal when oxidized
in human body, so important dietary
ingredient
• Best form of stored energy in body in adipose
tissues
• Fat soluble vitamins &
• Essential fatty acids are carried in fat of
natural food
• Decrease gastric motility[decrease hunger
level]
• High satiety value

6. 6
Biological importance 2
• Stored in adipose tissues under skin &
around organs,
– Thermal insulator
– protecting, supporting them
– also gives contours to body
• Electrical insulator
in myelinated nerves, cause rapid
propagation of depolarization wave

7. 7
• Combination of lipids & proteins in
mitochondria & cell membrane are important
constituent.
• lipoproteins is way of transporting lipids in
blood
• Precursors of e.g cholesterol & vitamin D3
• Receptors
• function in signal transduction
• Blood group specificity, organ & tissue
specificity as well
• Hormone like function

8. 8
Biomedical importance
• Study of lipid biochemistry necessary in
understanding
– Atherosclerosis
– Obesity
– Diabetes mellitis
– Hyperlipidemias
– Hyperglycaemias
– Role of polyunsaturated fatty acids in
nutrition & health

9. 9
No single internationally accepted Classification
Lipids in diet
TRIACYLGLYC
EROL :MOST
OF DIETARY
CONSTITUENT.
PHOPHOLIPIDS
CHOLESTEROL

10. 10
Classification of lipids
• SIMPLE LIPIDS
• COMPOUND or COMPLEX
LIPIDS
• DERIVED, PRECURSOR or
ASSOCITED LIPIDS

11. 11
lipids
simple compound derived
fats waxes phospholipids Nonphospholipids
Glycolipids
sulfolipids
SphingophospholipidsglyceroPhospholipids

12. 12
SIMPLE LIPIDS
Esters of fatty acids & alcohol
fatty acids & alcohol may differ
Esters
compound formed by condensation
of an acids & alcohol

13. 13
Esters formation
R-COOH + R-OH
O
//
H2O + R - C -O-R

14. 14
SIMPLE LIPIDS
1. Fats
2. Waxes
Fats
• Are Esters of fatty acids & alcohol
Glycerol
• Oils are fats in liquid state
• Neutral fats, triglycerides,
triacylglycerol - same

15. 15
waxes
• Are Esters of fatty acids & alcohol other
than glycerol
• Higher molecular weight monohydric
alcohol is present

16. 16
Phospholipids
1. GlyceroPhospholipids
Glycerol (alcohol)
+ fatty acids + phosphate
2. Sphingophospho lipids
Sphingosine (alcohol)
+ fatty acids + phosphate

17. 17
DERIVED, PRECURSOR or
ASSOCIATED LIPIDS
Include
• Hydrolytic product of above mentioned
compound
Diacyle glycerol
• Precursor
Sterols
• Associated
Prostaglandin

18. 18
Fatty acids

19. 19
Fatty acids(structure)

20. 20
Fatty Acids as Stored Energy
• Fatty acids are the body’s
principal form of stored energy
• Carbon almost completely
reduced as CH2
• Very closely packed in storage
tissues - not hydrated as sugars
are

21. 21
Dietary Fatty Acids
• Comprise 30-60% of caloric
intake in average American diet
• Triacylglycerols, phospholipids,
sterol esters
• Principal sources: dairy products,
meats

22. 22
Fatty acids structure
• Hydrocarbon chain with carboxylic
group at one end (Monocarboxylic acid)
• Ranging in chain length from 4 to
usually 24 Carbon atoms
• Occurring in Triglycerides
• Generally contain even number of
Carbon atoms
• Below 8 C chain are liquid at room
temperature

23. 23
structure of Fatty Acids
•At physiologic pH, the COOH group ionizes
to COO- ( pKa ~ 4.8 for COOH)
•Physical & physiological properties of
fatty acids reflect chain length & degree
of unsaturation
• Short and medium chain FAs are
amphipathic (both hydrophilic and
hydrophobic regions) and partially
soluble in water

24. 24
• Long chain fatty acids are highly
insoluble in water
(must be transported in association
with plasma proteins)
• Unusual fatty acids with branched or
ring-containing chains are found in
some species

25. 25
functions
• Stored as Triacylglycerols
• Function as one of the major fuel
sources for energy
• Essential fatty acids
• Precurssor of Eicosanoids

26. 26
Types of fatty acids
Fatty acids
Essential Saturated
UnsaturatedNon-essential
Cis isomer Trans isomer
Odd chain
Even Chain
Straight
Branched
Short chain
Medium
Long

27. 27
Saturated
• Fatty acids chains that contain
only carbon-carbon single bonds
Unsaturated
• Those molecules that contain
one or more double bonds

28. 28
Palmitic acid 16 : 0 CH3(CH2)14COOH
16 15 14 13 12 11 10 9 8 7 6 5 4 3 2 1O
H H H H H H H H H H H H H H H //
H-C–C–C–C–C–C–C–C–C–C–C–C–C–C–C–C-
OH
H H H H H H H H H H H H H H H
ω β α

29. 29
Abbreviations for fatty acids (16 : 1 ∆9
)
• The number to the left of the colon is
the total number of carbon atoms
• and the number to the right is the
number of double bonds.
• A superscript denotes the placement of
a double bond.
• For example, ∆9 signifies that there is a
double bonds between carbons 9 and
10.

30. 30
Palmitoleic acid 16 : 1 ∆9
16 15 14 13 12 11 10 9 8 7 6 5 4 3 2 O
H H H H H H H H H H H H H H H //
H-C–C–C–C–C–C–C–C–C–C–C–C–C–C–C–C-
OH
H H H H H H H H H H H H H

31. 31
Isomeric forms: Cis and trans
• double bonds are rigid structures,
molecules that contain them can occur
in two isomeric forms
Cis-isomers
• similar or identical groups are on the
same side of a double bond.
Trans-isomer
• groups are on opposite sides of a
double bond

32. 32
• The double bonds in most naturally
occurring fatty acids are in a cis
configuration.
• The presence of a cis double bond
causes an inflexible “kink” in a fatty acid
chain.

33. 33
Isomeric forms of unsaturated fatty acids
CH3 COOH COOH
R R R H
C=C C=C
H H H R
CH3
Cis. Isomer Trans isomer
1200

34. 34
O
॥
C-O-
O
॥
C-O-
Saturated bonds
unsaturated bonds
Cis configuration
Saturated fattyacid unSaturated fattyacid

35. 35
• Because of KINk unsaturated fatty acids
do not pack as closely together as
saturated fatty acids.
• Less energy is required to disrupt the
intermolecular forces between
unsaturated fatty acids.
• Therefore, they have lower melting points
and are liquids at room temperature.
• For example, a sample of palmitic acid
(16:0), a saturated fatty acid, melts at
63o
C, whereas palmitoeic acid (16:1∆9
)
melts at 0o
C.

36. 36
• Fatty acids with one double bond
monounsaturated
• two or more double bonds occur in fatty
acids usually separated by methylene
groups (-CH2-), they are
polyunsaturated.
• The monounsaturated fatty acid oleic
acid (18:1∆9
) and the polyunsaturated
linoleic acid (18:2∆9, 12
) are among the
most abundant in living organisms.

37. 37
• presence of one or more double bonds
in a fatty acid makes it susceptible to
oxidative attack.
• tendency of oils to become rancid.

38. 38
Some naturally occurring saturated fatty
acids in animals
Name
No. of
carbon
structure
abbreviat
ion
Palmitic
acid
16 CH3(CH2)14COOH 16:0
Stearic
acid
18 CH3(CH2)16COOH 18:0
Arachidic
acid
20 CH3(CH2)18COOH 20:0

39. 39
Some naturally occurring unsaturated fatty
acids in animals
name No. of
carbo
n
Structure (sat)x Abbreviat-
ion
oleic
acid
18
CH3(CH2)16COO
H
18:1∆9
linoleic
acid
18 CH3(CH2)16COO
H
18:2∆9,12
Arachid-
onic acid
20 CH3(CH2)18COO
H
20:4∆5,8,1
1,14

40. 40
Essential Fatty Acids
• Organisms such as plants and bacteria
can synthesize the entire fatty acids
they require.
• Mammals obtain most of their fatty
acids from dietary sources. However,
these organisms can synthesize
saturated fatty acids and some
monounsaturated fatty acids. They can
also modify some dietary fatty acids by
adding two-carbon units and introducing
some double bonds.

41. 41
Definition
• Nonessential Fatty acids that can be
synthesized in body
• Essential fatty acids must be obtained
from the diet, Because mammals do not
possess the enzymes required to synthesize
them
• linoleic (18:2∆9, 12
)
• linolenic (18:3∆9, 12, 15
) acids
• Arachidonic acid(20:4∆5,8,11,14
)

42. 42
Linolenic acid:
CH3-CH2-CH=CH-CH2-CH=CH-CH2-CH=CH-(CH2)7-COOH
• Linoleic Acid has 2 instead of 3 double
bonds
• Arachidonic and Eicosapentaenoic
acids produced from these.
• Some species not able to do these
conversions.

43. 43
sources
• Rich sources of essential fatty acids
include some vegetable oils, nuts, and
seeds.
• Linoleic and linolenic – green plants,
animal fats, seed oils
• Arachidonic – not found in plants.

44. 44
Functions
• Important in cell membranes,
contributing to proper membrane
structure,
• linolenic and linoleic acids are
precursors of several important
metabolites.
• The most-researched examples of fatty
acid derivatives are the eicosanoids i.e
Precursors for prostaglandins and
leukotrienes

45. 45
Essential Fatty Acids
• Discovered when animals fed on fat
free diets but
• adequate energy, protein, minerals, and
vitamins developed symptoms.
• Symptoms disappeared with addition of
fat.
• Animals cannot make some double
bonds, so fatty acids required in the
diet.

46. 46
Deficiency Symptoms
• Loss of hair
• Dermatitis
• Poor growth and reproduction
• kidney problems
• Poor healing
• Dehydration
• Degeneration of liver
• Immune system failure
• Thrombocytopenia [ a relative decrease

47. 47
Reactions of fatty acids
1. Esters formation
• Fatty acids react with Alcohols to form
Esters
• This reactions reversible; that is, under
appropriate conditions a fatty acid Ester
can react with water to produce a fatty
acid and an alcohol.

48. 48
2. Hydrogenation reactions
• Unsaturated fatty acids with double bonds
can undergo hydrogenation reactions to form
saturated fatty acids.
3. Oxidative attack
• unsaturated fatty aids are susceptible to
oxidative attack.
• Rancidity, development of unpleasant odour
& taste in lipids when exposed to air due to
ketoacids & short chain fatty acids

49. 49
Reactions of fattyacids
4. Acylated proteins
• Certain fatty acids (primarily myristic
and palmitic acids) are covalently
attached to a wide variety of eukaryotic
proteins.
• Fatty acids are transported from fat
cells to body cells esterified to serum
proteins and enter cells via acyl transfer
reactions.

50. 50
Simple lipids
Triacylglycerol
waxes

51. 51
Structure of triacylglycerols
• Tricylglycerols are esters of glycerol
with three fatty acid molecules
• Glycerides with one or two fatty acid
groups, called Monoacylglycrols and
Diacylglycerols, respectively, are
metabolic intermediates. They are
normally present in small amounts

52. 52
O
॥ ester
O CH2-O- C- R1 bond
॥
R2 -C-O-CH O
॥
CH2-O- C-R3
Triacylglycerol

53. 53

54. 54
Structure of Triacylglycerols(TAG)
• The carboxyl group of Three fatty acid
is joined to glycerol through a covalent
bond (ester)
• Most triacylglycerol molecules contain
fatty acids of varying lengths, which
may be unsaturated, saturated, or a
combination
• Loss of negative charge generates
“neutral fat”

55. 55
• FAs of TGs usually vary:
•fatty acid on carbon 1 is usually
saturated
•fatty acid on carbon 2 usually
unsaturated
• fatty acid on carbon 3 can be
either saturated or
unsaturated

56. 56
• Carbon 1 & 3 of glycerol are not
identical (3 D structure)
• Enzyme can distinguish them
readily & are specific to them
• Example,
Glycerol is always phosphorylated
at C # 3 by Glycerol kinase

57. 57
• Depending on their fatty acid
compositions, TAG mixtures referred to
as fats or oils.
• Fats, solid at room temperature,
contain a large proportion of saturated
fatty acids.
• Oils are liquid at room temperature
because of their relatively high
unsaturated fatty acid content
• Unsaturated FAs decrease Tm

58. 58
• In animals, Triacylglycerol (usually
referred to as fat) have several roles.
storage
• Major
• Triacylglycerol molecules store energy
more efficiently than glycogen for
several reasons:

59. 59
Triacylglycerol, best form of energy stores.
1. Because Triacylglycerol are
hydrophobic, they coalesce into
compact, anhydrous droplets.
• Glycogen (the other major energy
storage molecule) binds a substantial
amount of water
• Triacylglycerols store an equivalent
amount of energy in about one-eighth
glycogen’s volume.

60. 60
Triacylglycerol,best form of energy stores.
2. Triacylglycerol molecules are less
oxidized than carbohydrate
molecules. Therefore, triacylglycerols
release more energy (38.9 kj/g of fat
compared with 17.2 kj/g of
carbohydrate) when they are
degraded.

61. 61
Insulation
• A second important function of fat is to
provide insulation in low temperatures.
Fat is a poor conductor of heat.
Because adipose tissue, with its high
triacylglycerol content, is found
throughout the body (especially
underneath the skin), it prevents heat
loss.

62. 62
• Are Carrier of fatty acids.
• Finally, in some animals fat molecules
secreted by specialized glands make
fur or feathers water-repellent.

63. 63
Triacylglycerols in plants,
• In plants, Triacylglycerols constitute an
important energy & and fatty acids
(e.g., oleic and linoleic), reserve (plant
oils)
• Seeds rich in oil include peanut, corn,
palm, sunflower, and soybean. Olives
have high oil content

64. 64
WAX ESTERS
• Esters composed of long-chain fatty
acids and long-chain alcohols are
prominent constituents of most waxes.
• They are protective coatings on leaves,
stems, and fruits of plants and the skin
and fur of animals.

65. 65
Examples of waxes
• Well-known examples of waxes include
carnauba wax, produced by the leaves
of the Brazilian wax palm, and
Beeswax.
• Triacontyl hexadecanoate is one of
several important wax esters in
beeswax.
• Waxes also contain aldehyde and
sterols (steroid alcohol).

66. 66
Compound lipids
1. PHOSPHOLIPIDS
2. NON-PHOSPHOLIPIDS

67. 67
COMPOUND or COMPLEX LIPIDS
Esters of fatty acids & alcohol containing
an additional group. subdivided as,
1. Phospholipids
additional group is phosphate
2. Nonphospholipids
– Glycolipids
– Sulfolipids
– Gangliosides

68. 68
PHOSPHOLIPIDS (Biological role)
• They are first and foremost structural
components of membranes.
• Several phospholipids are emulsifying agents
and surface active agents.
• (A surface active agent is a substance that
lowers the surface tension of a liquid, usually
water, so that it spreads out over a surface.)
Phospholipids are suited to these roles
because they are Amphipathic molecules.

69. 69
Amphipathic
• Despite their structural differences, all
phospholipids have hydrophobic and
hydrophilic domains.
• The hydrophobic domain is composed
largely of the hydrocarbon chains of
fatty acids;
• the hydrophilic domain, called a polar
head group, contains Phosphate and
other charged or polar groups.

70. 70
• When phospholipids are suspended in water,
they spontaneously rearrange into ordered
structures.
• Phospholipids hydrophobic groups are buried in
the interior to exclude water. Simultaneously,
hydrophilic polar head groups are oriented so
that they are exposed to water.
• When Phospholipids molecules are present in
sufficient concentration, they form bimolecular
layers. This property of phospholipids (and other
amphipathic lipid molecules) is the basis of
membrane structure

71. 71
There are two types of phospholipids
1. GlyceroPhospholipids
Phosphoglycerides Glycerol (alcohol)
+ fatty acids + phosphate
2. Sphingophospho lipids
sphingocyelins.
Sphingosine (alcohol)
+ fatty acids + phosphate

72. 72
GlyceroPhospholipids
Phosphoglycerides are the most
numerous phospholipids molecules
found in cell membranes.
• Phosphatidic acid
• Phosphatidyl cholin (Lecithin)
• Phosphatidyl ethanolamin
• Phosphatidyl Serine
• Cardiolipin
• Plasmalogen

73. 73
GlyceroPhospholipids (cont)
• Phosphatidyl Inositol
• Platelete activating factor

74. 74
Membrane Phospholipids
• Phosphatidyl choline is major lipids
• Outer membrane --- Phosphatidyl
Choline & Sphingomyline are
dominant
• Inner membrane---Phosphatidylserine
& Phosphatidyl ethanolamine
• Phosphatidyl inositol (only in inner
membrane) as second messenger

75. 75
• The most common fatty acids in the
Phosphoglycerides have between16
and 20 carbons.
• Saturated fatty acids usually occur at C-
1 of glycerol.
• The fatty acid substituent at C-2 is
usually unsaturated.

76. 76
O
॥
O CH2-O- C-R1
॥
R 2-C-O-CH O
॥
CH2-O- P-O-
।
O-
Phosphatidic Acid

77. 77
Phosphatidic acid
• The simplest Phosphoglyceride,
• is the precursor for all other
Phosphoglyceride molecules.
• is composed of Glycerol-3-phosphate
that is esterified with two fatty acids.
• Phosphoglyceride molecules are
classified according to which
nitrogenous base becomes esterified to
the phosphate group.

78. 78
O
॥
O CH2-O- C-R1
॥
R 2-C-O-CH O
॥
CH2-O-P-O–
-CH2CH2N+
(CH3)3
।
O-
Phosphatidyl cholin
(Lecithin)

79. 79
Lecithin
• Membrane sturcture.
• Abundant PL in serum & bile
• Amulsifying agent
• Is part of Surfactant on alveolar membranes,
lower surface tension.
• Synthesized in later period of pregnancy
• Premature birth may results in lung collapse
• Respiratory distress syndrome

80. 80
Clinical corelation
• Lecithin/Sphingomyelin ratio in amniotic
fluid predicts about lung function &
hence survival of baby before delivery

81. 81
O
॥
CH2-O- C-R1
OH-CH O
॥
CH2-O-P-O-CH2CH2N+
(CH3)3
।
O-
Lysophosphatidyl cholin
(LysoLecithin)

82. 82
LysoLecithin
• Enzymatic removal of fatty acid from C1 or
C2 of lecithin
• 1 acyl radical only
• Important in interconversion &
metabolism of phospholipids
• Phospholipase A, is present in snake venom
• LysoLecithin causes hemolysis of
erythrocytes
• Found in oxidized lipoproteins,implicated in
some of their effects in promoting
atherosclerosis

83. 83
O
॥
O CH2-O- C-R1
॥
R 2-C-O-CH O
॥
CH2-O-P-O-CH2CH2-NH3
+
।
O-
Phosphatidyl
Ethanolamin(Cephalin)

84. 84
Phosphatidyl Ethanolamin (Cephalin)
• Resembles Lecithin in function & found
in association with it
• Head groups differ
• Named, separated in high concentration
from brain tissues

85. 85
O
॥
O CH2-O- C-R1
॥
R 2-C-O-CH O NH3
+
॥ ।
CH2-O-P-O-CH2CH
। ।
O-
COO-
Phosphatidyl Serine

86. 86
O O
॥ ॥
O CH2-O- C-R1R 4-C-O-CH O
॥ ॥
R 2-C-O-CH O CH2-O- C-R3
॥ OH
CH2-O- P-O-CH2-C-CH2-O- P-CH2
। H
O-
Cardiolipin

87. 87
Cardiolipin
• Diphosphatidyl glycerol
• 2 phosphatidic acid esterified through
phosphate to a glycerol
• Only GPL in human i-e antigenic
• In inner mitochondrial membrane

88. 88
O H2C-O- CH=CH-R1
॥
R 2-C-O-CH O
॥
CH2-O-P-O–
-CH2CH2-NH3
+
।
O-
Plasmalogen
(Phosphatidyl
Ethanolamin)
Ether linkage

89. 89
Plasmalogen (Phosphatidyl Ethanolamin)
• Carbon 1 of glycerol has a vinyl ether
instead of fatty acid
• Unsaturated alkyl group
• Otherwise identical to Phosphatidyl
Ethanolamin & Cholin
• Skeletal muscle, brain(10%), heart liver
& platelets
• Resistant to Phosoholipases

90. 90
Platelets activating factor (PAF)
• Is a related to Plasmalogen compound
• vinyl ether with saturated alkyl group at
C1 & Acetyl at C2
• One of most potent biomolecule
• Released from Basophils
• Binding to receptors triggers potent
– Thrombotic
– Inflammatory events

91. 91
PAF
• Stimulates the aggregation of Platelets
• Helps in clotting of blood
• Mediates
– hypersensitivity
– Anaphylactic shock
– Acute inflammatory reaction
• stimulates inflammatory cells to produce
superoxides to kill becteria

92. 92
Phosphatidylinositol (2nd
messanger)
• Phosphatidyl-4,5-bisphosphate
(PIP2) A derivative of
phosphatidylionositol, is found in plasma
membranes, in only small amounts.
• PIP2 is now recognized as an important
component of intracellular signal
transduction.
• The Phosphatidylinositol cycle, initiated
when certain hormones bind to
membrane receptors
• Carrier of Arachidonic acid in membrane

93. 93
SPHINGOLIPIDS
• Sphingolipids are important
components of animal and plant
membranes.
• All sphingolipid molecules contain long-
chain amino alcohol.
• In animals this alcohol is primarily
sphingosine.
• Phytosphingosine is found in plant
sphingolipids.

94. 94
OH O
। H ॥
CH3-(CH2)12-CH=CH-CH-CH-N-C-R
।
CH2
।
O
।
O=P-O-
।
Sphingomyelin O- CH2- CH2-N (CH3)
Fatty acidSphingosine
Ceramide
Choline

95. 95
Ceramide
• The core of each type of Sphingolipid is
Ceramide
• a fatty acid amide derivative of
sphingosine.
• In Sphingomyelin, the 1-Hydroxyl group
of Ceramides esterified to the
Phosphate group of Phosphorylcholine
or Phosphorylethanolamine.

96. 96
Sphingomylein
• Is found in most animal cell membranes.
• However, as its name suggests,
Sphingomyelin is found in greatest
abundance in the Myelin sheath of
nerve cells. (The myelin sheath is formed
by successive wrappings of the cell
membrane of a specialized myelinating
cell around a nerve cell axon.
• Its insulating properties facilitate the rapid
transmission of nerve impulses.

97. 97
Non phospholipids (Glycosphingolipids)
• The Ceramides are also precursors for
the Glycolipids or Glycosphingolipids.
• In Glycolipids a monosaccharide,
disaccharide, or oligosaccharide is
attached to a ceramides through an O-
glycosidic linkage.
• Glycolipids also differ from
Sphingomyelin in that they contain no
phosphate
• Particularly in outer leaf of plasma
memb

98. 98
OH
। H
CH3-(CH2)12-CH=CH-CH-CH-N-
O-CH2
Fattyacid
Sphingosine
Ceramide
HH
H
H
H
CH2OH
OH
OH
OH
O
Galactose
Galactocerebroside

99. 99
Glycolipid classes
• The most important glycolipid classes
are the
• Cerebrosides
• Sulfatides
• Gangliosides

100. 100
Cerebrosides (Neutral)
• Are Sphingolipids in which the head group is
a monosaccharide.
• These molecules, unlike phospholipids, are
nonionic.
• Galactocerebrosides the most common
example of this class, are almost entirely
found in the cell membranes of the brain, may
contain Cerebronic acid(C24)
• Globosides (Lactosylceramide)

101. 101
Sulfatide (Acidic)
• If a Cerebroside is sulfated, it is referred
to as a sulfatide.
• Sulfatides are negatively charged at
physiological pH.
• Found in nerve tissue & kidneys

102. 102
Gangliosides (Acidic)
• Sphingolipids that possess
Oligosaccharide groups with one or more
Sialic acid residues are called
Gangliosides
• Although were first isolated from nerve
tissues, they also occur in most other
animal tissues.

103. 103
Name of Gangliosides
• This includes subscript letter and
numbers.
• The letters M, D, and T indicate whether
the molecule contains one, two, or three
sialic acid residues respectively.
• The number is designated on basis of
chromatographic migration
• The Tay-Sachs Ganglioside is GM2

104. 104
• Certain Glycolipid molecules may bind
bacterial toxins, as well as bacterial cells,
to animal cell membranes.
• For example, the toxins that cause
Cholera, Tetanus, and Botulism bind to
Glycolipid cell membrane receptors.
• The role of Glycolipids is still unclear.

105. 105
• Bacteria that have been shown to bind
to Glycolipid receptors include
• E. Coli, Streptococcus pneumoniae,
and Neisseria Gonorrhoenae,
• the Causative agents of urinary tract
infectons, pneumonia, and gonorrhea,
respectively.

106. 106
SPHINGOLIPID STORAGE
DISEASES
• Each Lysosomal storage disease is
caused by a hereditary deficiency of an
enzyme required for the degradation of
a specific metabolite.
• Several Lysosomal storage diseases
are associated with Sphingolipid
metabolism.
• Most of these diseases, also referred to
as the Sphingolipidoses, are fatal.

107. 107
Tay-Sachs disease
• The most common Sphingolipid storage
disease
• is caused by a deficiency of β-
hexosaminidase A, the enzyme that
degrades the ganglioside GM2.
• As cells accumulate this molecule, they
swell up

108. 108
Tay-Sachs disease
• blindness, muscle weakness, seizures,
and mental retardation) usually appear
several months after birth.
• Because there is no therapy for Tay-
Sachs disease or for any other of the
sphingolipidoses the condition is always
fatal (usually by age 3)

109. 109
Other SPHINGOLIPID STORAGE
DISEASES
• Niemann-Pick disease
– Sphingomyleinase deficiency
– Liver & spleen filled with lipids,
enlarged
– Neurodegeneration
• Gaucher disease
• Fabry disease
• GM1 Gangliosidosis

110. 110

111. 111

112. 112
DERIVED, PRECURSOR or
ASSOCITED LIPIDS
Steriods
Eicosanoides
Lipoproteins

113. 113
Steroids
• are complex derivatives of Triterpenes.
• They are found in all eukaryotes and a
small number of bacteria.
• Each type of steroid is composed
of four fused rings.
• Perhydrocyclopantanophenanthren
e
• Steroids are distinguished from each
other by the placement of carbon-carbon
double bonds and various constituents
• Cholesterol important example

114. 114
Cholesterol
CH3 CH2 CH2 CH3
CH CH2 CH
CH3
C D
A B
HO
CH3
CH3
1
2
3
4
5
6
7
8
9
27
10

115. 115
Cholesterol
• Cholesterol possesses a branched
hydrocarbon side chain at C-17.
• hydroxyl group attached to C-3), it is
classified as a sterol.
• is usually stored in cell as a fatty acid
Eester.
• Abundant in adrenal glands nervous
system
• 140 gm in normal adult

116. 116
Cholesterol
• Normal blood level
150 -200 mg / dl
• 200 mg / dl is taken as
maximum desirable
upper limit

117. 117
Cholesteryl ester
CH3 CH2 CH2 CH3
CH CH2 CH
CH3
C D
A B
Fattyacid-O
CH3
CH3
1
2
3
4
5
10
6
7
8
9
27

118. 118
• This esterification reaction is
catalyzed by the enzyme
Acyl-CoA:Cholesterol acyl
Transferase
(ACAT), located on the cytoplasmic
face of the endoplasmic reticulum.

119. 119
Cholesterol (function)
1. Stability of phospholipid bilayers
(membranes)without affecting fluidity
2. Precursor of bile salts (lipid digestion
& absorption)
3. Precursor of all steroid hormones
4. Precursor of Vitamin D
(7 dehydrocholestrol)
3. Precursor of Cardiac glycosides

120. 120
Cardiac glycosides
• Molecules that increase the force of
cardiac muscle contraction, are among
the most interesting steroid derivatives.
• Glycosides are carbohydrate-containing
acetals. Although several cardiac
glycosides are extremely toxic e.g.,
ouabain, others have valuable
medicinal properties.
• For example, Digitalis, an extract of the
dried leaves of Digitalis purpurea is a
time-honored stimulator of Cardiac
muscle contracton.

121. 121
Digitoxin
• Digitoxin, the major “cardiotonic”
glycoside in digitalis, is used to treat
congestive heart failure (an illness in
which the heart is so damaged by
disease processe that pumping is
impaired).
• In higher than therapeutic doses,
Digitoxin is extremely toxic.

122. 122
Lipoprotein

123. 123
Lipoprotein
• Group of molecules transporting lipids in the
bloodstream from one organ to another
• Composition
– Triacylglycerols
– Phospholipids
– Cholesterol
– Proteins
• Lipoproteins also contain several types of
lipid-soluble vitamins (α-tocopherol and
several carotenoids).
• The protein components are called
apolipoprotiens or apoproteins.

124. 124
Plasma
Lipoprotein

125. 125
Types of lipoproteins
• Lipoprotiens are classified (named)
according to their
1. Density
2. Electrophoretic mobility

126. 126
Density
There are six lipoproteins
1. Chylomicrons
2. Chylomicron remnants
3. VLDL
4. VLDL remnants or IDL
5. LDL and
6. HDL.

127. 127
Electrophoretic mobility
• Chylomicron
• β lipoproteins
• Pre β lipoproteins
• α lipoproteins

128. 128

129. 129

130. 130
0%
20%
40%
60%
80%
100%
Chylo-
microns
VLDL LDL HDL
Lipoprotein Type
Composition
C
P
T
C
P
T
T
P
C
C
P
T
Figure 2. The major classes of lipoproteins and their relative content of
triacylglycerol (T), cholesterol (C) and protein (P).

131. 131
Chylomicron
TAG
85%
Ph.lipid9%
cholesterol
1%
Ch.Esters3%
Protein2% TAG
Ph.lipid
Protein
Ch. esters
cholesterol
othersApo C-II
Apo B-48
Apo E

132. 132
Chylomicrons
• are large lipoproteins
• of extremely low density
• transport dietary Triacylglycerols and
Cholesteryl esters from the intestine to
muscle and adipose tissues.

133. 133
Very Low Density Lipoproteins
TAG
50%
Ph.lipid
18%
others
3%
cholesterol
7%
Ch.esters
12%Protein
10%
TAG
Ph.lipid
Protein
Ch. esters
cholesterol
others
Apo C-II
Apo B-100
Apo E

134. 134
Very low density lipoproteins (VLDL)
• 0.95-1.006 g/cm3
• Synthesized in the liver
• Transport lipids to tissues.
• As VLDL are transported through the
body they become depleted of
Triacylglycerols, some Apoproteins &
Phospholipids
• The Tricylglycerol-depleted VLDL
remnants are either picked up by the Liver
or converted to low-density lipoproteins

135. 135
Low density Lipoproteins
Protein
24%
Ch.esters
38%
cholesterol
8%
Ph.lipid
20%
TAG
10%
TAG
Ph.lipid
Protein
Ch. esters
cholesterol
others
Apo B-100

136. 136
Low-density lipoproteins (LDL)
• (1.006-1.063 g/cm3)
• LDL carry Cholesterol to tissues
• In a complex process, LDL are engulfed
by cells after binding to LDL receptors.
• elucidated by Michael Brown and
Joseph Goldstein recipients of the 1985
Nobel prize

137. 137
HDL High Density Lipoproteins
TAG
4%
Ph.lipid
24%
cholesterol2%
Ch.esters
15%
Protein
55%
TAG
Ph.lipid
Protein
Ch. esters
cholesterol
others
Apo C-II
Apo E
Apo A

138. 138
High-density lipoprotein (HDL)
• 1.063-1.210 g/cm3
• also produced in the liver
• appears to be the scavenging of
excessive cholesterol from cell
membranes.

139. 139
Scavenger role of HDL
• Cholesteryl esters are formed when the
plasma enzyme lecithin: cholesterol
acyltransferase (LCAT) transfers a fatty acid
residue from lecithin to cholesterol.
• It is now believed that HDL transports these
cholesteryl esters to the liver.
• Liver, the only organ that can dispose
of excess cholesterol, converts most of it
is to bile acids.

140. 140
Lipids And Atherosclerosis

141. 141
ATHEROSCLEROSIS:
• Atherosclerosis is a chronic disease in which
soft masses, called Atheromas (plaque),
accumulate on the inside of arteries
• is a progressive process, smooth muscle cells,
macrophages, and various cell debris build up.
• macrophages fill with lipid (predominantly
Cholesterol and Cholesrteryl esters derived
from LDL), take a foam like appearance, Foam
cells.
• deposits mechanically damaged artery wall

142. 142
• Eventually, atherosclerotic plaque may
calcify and protrude sufficiently into
arterial lumens. the blood flow is
impeded.
• Disruption of vital organ functions,
especially those of the brain, heart, and
lungs caused by oxygen and nutrient
deprivation
• In coronary artery disease, one of the
most common consequences of
atherosclerosis, this deprivation
damages heart muscle

143. 143
Plasma LDL & HDL
• Because most of the cholesterol found
in plaque is obtained by the ingestion of
LDL by foam cells, high plasma LDL
levels are directly related with high risk
for coronary artery disease.
(LDL have a high cholesterol and
cholesteryl ester content)

144. 144

145. 145
Plasma LDL & HDL
• In contrast, a high plasma HDL level is
considered to be associated with a low risk
for coronary artery disese.
• Liver cells (hepatocytes) are the only cells
that possess HDL receptors
• Other high risk factors include
– a high-fat diet
– Smoking
– Stress
– sedentary lifestyle

146. 146
• The most important bile acids are
1. Cholic acid
2. Chenodeoxycholic acid.
 Cholesterol is precursor of bile salts
 In liver
 Required for lipid digestion & absorption
BILE ACIDS AND SALTS

147. 147
ketone bodies
• There are three compounds grouped
under the term ketone bodies; these are
• Acetoacetic acid
∀β- Hydroxybutyric acid
• Acetone

148. 148

149. 149
EICOSANOIDS

150. 150
EICOSANOIDS
• Compounds derived from 20 C
polyunsaturared fattyacid Arachidonic
acid
• 20:4 (5, 8, 11, 14)
• Linoleic acid is dietery precurssor,
elongated & desaturated in body to
Arachidonic acid
• Arachidonic acid is stored in the
membranes as Phosphatidylionositol

151. 151
Eicosanoids
Include
• Prostaglandins (PG)
• Thromboxanes (TX)
• Leukotrienes (LT)
• Prostacyclins

152. 152
Salient features
• Hormone like action But
• Produced in small amount
• By almost all tissues
• Act locally
• Extremly short half life, not stored
• Performing variable function in different
tissues depending upon receptor they bind
with
• Responses are physiologic as well as
pathologic

153. 153
Structures of a few different arachidonic acid derivatives

154. 154

155. 155
In general: regulate local inflammation but each
molecule has specific effects
eg. Prostaglandin E2 - vasodilator
Prostaglandin F2 - vasoconstriction
Prostacyclin (PGI2) - vasodilator / inhibits
platelet aggregation
Thromboxane A2 - vasoconstrictor /
stimulates platelet aggregation
Different prostaglandins are made by different cell
types.
eg. Thromboxane A2 is made in platelets
Prostacyclin is produced by vascular
endothelial cells

156. 156
Functions (examples)
TXA2 in Platelets
• aggregation of Platelets
• Vasoconstriction
• Contraction of smooth muscles
PGl2 in endothelium
• Vasodilation
• Inhibition of aggregation of Platelets
Opposing action limits Thrombi
formation------- Al-Mizan

157. 157
PGF2 most tissues
• Vasoconstriction
• Contraction of smooth muscles
• Contraction of uterine muscles
PGE2 most tissues
• Vasodilation
• Relaxation of smooth muscles
• Used to induce labour ,Contraction of
uterine muscles

158. 158
Chemistry of Lipids

159. 159
Role of Eicosanoids
• Mediating inflammation
• Fever
• Allergic response
• Gastric integrity
• Renal function
• Ovarian & uterine function
• Bone metabolism
• Nerve & brain
• Smooth muscle regulation
• Platelets homeostasis

160. 160
Eicosanoids & disease
• Inflammation
Vasodilatation & ↑ capillary permeability
 edema & pain
Glucocorticoids used as Anti-
Inflammatory & Anti allergic
Reason
they inhibit Phospholipase A pathway of
Eicosanoids synthesis

161. 161
Aspirin & Eicosanoids
• Inhibits fever & pain
• In low doses prevents Myocardial
infarction
• Reason
it irreversibly inhibits synthesis of
Prostacylins & TXA2 so ↓ incidence of
Thrombo-embolism

162. 162
• Type 2 Diabetic patients show ↓ in
insulin secretion due to PGE2
• Peptic ulcer, PGE2 analogues
↓ HCl secretion
• Indomethazine drug tried in patent
Ductus Arteriosis. It inhibits the PG
synthesis (↑ secretion stops closure)

163. 163
• Bronchial asthma
Antigen/Antibody recation liberates
several Eicosanoids cause intense
reaction with Bronchoconstriction &
Broncho-odema

164. 164
Lipid peroxidation
&
Its significance

165. 165
Lipid peroxidation
• It is auto-oxidation when lipids are
exposed to oxygen
• Responsible for “ rancidity ” of fats
• Rancidity is deterioration in fat foods
& development of specific odour, color,
taste

166. 166
Peroxidation in the body
• In vivo, it causes damage
• Free radicals are produced during
peroxide formation from naturally
occurring polyunsaturated fatty acids
• It is a chain reaction

167. 167
Same
• Free radicals
• Superoxides
• Reactive oxygen species (ROS)
• Respiratory Burst
• Oxidative stress

168. 168
Peroxidation in the body
• Partial reduction of molecular Oxygen
• O2 diffuses rapidly in to & out of cells
because it is soluble in non-polar lipid core of
membrane
• It can accept single electron to form unstable
derivative.
– H2O2 Superoxide radical
– OH-
Hydroxyl Radical
– O-
single oxygen.

169. 169
• Dangerous to cell if formed in significant
amount.
• Antioxidant mechanism are the agents to
trap it, in organism to keep it at minimum
level
– Antioxidant enzymes & coenzymes
system e.g Glutathione, Catalase,
NADPH[(nicotinamide adenine
dinucleotide phosphate-oxidase]
– Antioxidant vitamins, A, C, E
Antioxidant mechanism

170. 170
Action of Glutathione
2 R-SH + H2O2  R-S-S-R + 2H2O
2 Glutathione-SH + H2O2
G Peroxidase G reductase
+NADPH+H+
G-S-S-G + 2H2O

171. 171
• Enzyme inactivation.
• Depolymerization of CHO
• Depolymerization of DNA
• Membrane destruction
Oxidative stress can result in

172. 172
Respiratory Burst
• Cells like macrophages, produce large
number of Free radicals, to kill the
bacteria & damaged cells
• Rapid consumption of molecular
Oxygen that accompanies formation of
Superoxides is called
Respiratory BurstRespiratory Burst

173. 173
Causes of Oxidative stress (↑ peroxidation)
• Metabolic abnormalities
• Overuse of some drugs, Alcohol
• Radiation
• Repeated contact with environmental
contaminations e.g Tobacco smoke
• ↓ level of Antioxidants

174. 174
• in addition to aging process,
Oxidative stress linked to 100 human
diseases, examples
• Cancer
• CVS disorders[Cyclic vomiting syndrome]
– Atherosclerosis
– Myocardial Infarction
– Hypertension
• Neorologial disorders
– Parkinson syndrome
– Alzheimer’s disease