2. Structure & Classification of lipids
Lipids:
– Heterogeneous group of organic substances in
plant & animal tissues
• Fats
• Oils
• Waxes
• Related compounds
– Related either actually or potentially to fatty acids
– Related by their solubility
– Esters of fatty acids with different alcohols
– Some of them may contain phosphoric acid,
nitrogenous base, proteins & carbohydrates
3. Bloor’s Criteria to define Lipids:
According to Bloor lipids:
–Insoluble in water
–Soluble in fat solvents, such as ether,
chloroform, benzene, acetone,…
–In relationship to fatty acids as either
actual or potential esters
–Possibility of utilization by living organisms
4. Biomedical Importance of Lipids
Lipids:
– Act as stored fuel in the body
• Superior to carbohydrates
– Yields more energy as compared to carbohydrates
(9.5 C/gm Vs 4.0 C/gm)
– Can be stored in body in almost unlimited amount in
contrast to carbohydrates
– Important dietary constituent
– Deposited under skin exert insulating effect
against low temperature in body
– Deposited around internal organs ( e.g., kidney)
provide padding & protection
5.
6. Polar Bears Use Triacylglycerols to
Survive Long Periods of Fasting
7. Whales and Arctic mammals rely on body fat for both insulation and energy reserves
8. Cont…
– Breakdown products can be utilized for building
biological active materials
– Supply “Essential fatty acids (EFA)”
• Cannot be synthesized in body
• Essential in the diet for normal health & growth
– Provide fat soluble vitamins: A, D, E & K
– Important constituents of biological membranes:
cell walls, cell membranes & cell organelles
• E.g., Lipoproteins, cholesterol esters & phospholipids
– Serve as „carriers‟ of TAG, cholesterol &
Phospholipids in body fluids
• E.g., Lipoproteins
9. Cont…
– Functions of Lipids as a Summary
– Excellent energy reserves
– Structure of cell membranes
– Organ padding
– Body thermal insulation
– Essential fatty acids (EFA)
– Hormone synthesis
– Fat soluble vitamin absorption
– Lipids also play important roles in signal-
transduction pathways
10. Classification of lipids
– Bloor‟s Classification is generally adopted with a
few modifications as follows:
• Simple Lipids
• Compound/Complex Lipids
• Derived Lipids
• Mixed lipids
• Simple Lipids:
– Esters of fatty acids with various alcohols:
• Neutral fats (Triacylglycerols, TAGs):
– Triesters of fatty acids with glycerol
11. Cont…
– Waxes
• Esters of fatty acids with higher monohydroxy
aliphatic alcohols
• True waxes are esters of higher fatty acids with
Cetyl alcohol (C16H33OH) or other higher
straight chain alcohols
– Cholesterol esters
• Esters of fatty acid with cholesterol
– Vit A esters
• Palmitic acid esters of Vit A (Retinol)
– Vit D esters
• Stearic acid esters of Vit D
12. Cont…
• Compound/Complex Lipids:
– Esters of fatty acids containing groups, other
than, & in addition to alcohol & fatty acids
• Phospholipids:
– Esters of fatty acids containing phosphoric acid
residues, nitrogenous bases & other substituent's
– E.g.,
» Phosphatidyl choline (Lecithin)
» Phosphatidyl ethanolamine (Cephalin)
» Phosphatidyl inositols (Lipositols)
» Phosphatidyl serine
» Plasmalogens
» Sphingomyelins
13. Cont…
– Glycolipids:
• Esters of fatty acids containing carbohydrate moiety
& nitrogenous base
• Do not contain phosphoric acid or glycerol
• Contain a special alcohol called sphingol or sphingosine,
instead of glycerol
• Are of two types:
– Cerebrosides
– Gangliosides
– Sulpholipids:
• Lipids characterized by possessing sulphate groups.
– Lipoproteins:
• Lipids as prosthetic group to proteins
14. Cont…
• Derived Lipids:
– Hydrolysis product of simple & compound lipids
• Fatty acids:
– May be saturated, unsaturated or cyclic
• Monoglycerides (MAG) & Diglycerides (DAG)
• Alcohols:
– Straight chain alcohols
» Water insoluble alcohols of higher molecular
weight
– Cholesterol & other sterols including Vit-D
– Alcohols containing β-ionone ring including Vit-A
– Glycerol
– Sphingosine
15. Cont…
• Miscellaneous (mixed) Lipids:
– Aliphatic hydrocarbons
• Found in liver fat, bees wax & plant waxes
• E.g., Isooctadecane found in liver fat
– Carotenoids
– Squalene
• Hydrocarbon found in shark, mammalian liver & in
human sebum
– Vitamins E & K
– Eicosanoids:
– Prostaglandins & prostacyclenes
– Thromboxanes
– Leukotrienes
16. Derived Lipids
Fatty Acids
– Building block molecules of almost all lipids
– Organic acids with long alkyl chain (C4 to C36)
and terminal carboxyl group
– Contain polar carboxylic acid „head‟ which is
hydrophilic and non-polar hydrocarbon ‘tail’
which is hydrophobic
– Differ among each other based on:
• Alkyl chain length
• Presence /absence of double bond
• Number & positions of double bonds
17.
18. Classification of Fatty Acids
• Based on alkyl chain length:
–Short chain fatty acids (4-6)
–Medium chain fatty acids (8-12)
–Long chain fatty acids ( 12-22)
–Very long chain fatty acid (>22)
• Based on presence / absence of
double bond
–Saturated Fatty Acids
–Unsaturated Fatty Acids
• Monounsaturated Fatty Acids
• Polyunsaturated Fatty Acids
19. Cont…
• Based on biological origins:
–Essential Fatty acids
–Non-essential Fatty acids
• Based on position & orientation of double
bonds
–Usual (Cis- oriented) Fatty acids
–Unusual (Trans- oriented) Fatty Acids
20. Cont…
• Saturated Fatty acids:
– Contain long aliphatic alkyl chain &terminal
carboxyl group
– Hypothetical short form structure is given by
CH3(CH2)nCOOH, where n=10,12,14,16,&18
• For Lauric acid
– Short form structure CH3(CH2)10COOH & C=12
• For Myristic Acid
– Short form structure CH3(CH2)12COOH & C=14
• For palmitic acid
– Short form structure CH3(CH2)14COOH & C=16
• For stearic acid
– Short form structure CH3(CH2)16COOH & C=18
21. Cont…
• For Arachidic acid
– Short form structure CH3(CH2)18COOH & C=20
– Saturated fatty acids with C=16 & C=18 are
most abundant in natural lipids
• Unsaturated Fatty Acids
– Contain long alkyl chain with one or more double
bonds & terminal carboxyl group
• Monounsaturated fatty acids:
– With only one double bond
– In most monounsaturated fatty acids of higher
animals a double bond is b/n C-9 & C-10
• Polyunsaturated fatty acids:
– With more than one double bonds
– Methylene (-CH2-) group separates first double
bond from next
22. Cont…
• Both unsaturated fatty acids contain methyl (CH3-)
oil-soluble Omega (ω)-end & carboxylic acid (-COOH)
water soluble Delta (Δ)-end
– Common monounsaturated fatty acids in higher
animals include:
• Oleic Acid:
– ω-9 fatty acid with 18-carbon atoms
– Short form structure
CH3(CH2)7CH=CH(CH2)7COOH & C=18
– Most abundant unsaturated FA in human beings
• Palmitoleic acid:
– ω-7 fatty acid with 16-carbon atoms
– Most abundant unsaturated FA in plants (peanuts,
cotton seeds & soyabeans)
– Short form structure
CH3(CH2)7CH=CH(CH2)5COOH & C=16
23. Cont…
– Common polyunsaturated fatty acids in higher
animals include:
• Linoleic acid
– ω-6 fatty acid with 18-carbon atoms
– Two double bonds at position 9 &12
– Short form structure
CH3(CH2)3(CH2CH=CHCH2)2(CH2)7COOH & C=18
Δ(9,12)
– Precursor molecule for ω-6 arachidonic acid
• α-Linolenic acid:
– ω-3 fatty acid with 18-carbon atoms
– Three double bonds at position 9, 12 & 15
– Short form structure
CH3(CH2CH=CHCH2)2CH=CH(CH2)6 COOH &
C=18 Δ(9,12,15)
– It gives rise to ω-3 fatty acids EPA and DHA
24. Cont…
• γ-Linolenic acid:
– ω-6 fatty acid with 18-carbon atoms
– Three double bonds at position 6, 9 & 12
– Short form structure CH3(CH2)3(CH2
CH=CHCH2)3CH2 COOH &C=18 Δ(6,9,12)
– Derived from linoleic acid by introduction of a
double bond at position 6 by the enzyme Δ-
desaturase
• Arachidonic acid:
– ω-6 fatty acid with 20-carbon atoms
– Four double bonds at position 5,8, 11 & 14
– short form structure CH3(CH2)3(CH2CH=CH)4
(CH2)3 COOH & C=20 Δ(5,8,11,14)
– Serves as precursor molecules in biosynthesis of
eicosanoids
25. Cont…
• Eicosapentaenoic acid (EPA):
– ω-3 fatty acid with 20-carbon atoms
– Five double bonds at position 5,8, 11,14 & 17
– Short form structure CH3CH2(CH2CH=CH)5
(CH2)2 COOH & C=20 Δ(5,8,11,14,17)
– Also serves as a precursor molecule in biosynthesis
of eicosanoids
• Docasahexaenoic Acid (DHA):
– ω-3 fatty acid with 22-carbon atoms
– Six double bonds at position 4,7,10,13,16 and 19
– Short form structure CH3CH2(CH=CHCH2)6CH2
COOH & C=22 Δ(4,7,10,13,16,19)
26. Cont…
• Essential Fatty acids:
– Fatty acids which higher animals including human
beings cannot synthesis but get through their
diet
– Higher animals cannot introduce double bonds
beyond C-9 counted from carboxyl carbon
• E.g., Linoleic acids & α-Linolenic acid
– Daietry source of EFA:
• Linoleic acids
– Corn oil, peanut oil, cottonseed oil, soya bean oil, egg yolk
• α-Linolenic acid
– Linseed oil, rapeseed oil, soya bean oil, fish oil
27.
28. Cont…
– Biomedical Importance of EFA
• Structural elements of tissues
– PUFA occur in higher conc. in lipids associated with
structural elements of tissues
– EFA serves as a precursor for synthesis of PUFA in
animals including human beings
• Structural element of gonads:
– PUFA occur in higher conc. in lipids of gonads
– EFA serves as a precursor for synthesis of PUFA in
animals including human beings
» This suggests importance of EFA in
reproductive function
29. Cont…
• Structural element of mitochondrial membrane
–A deficiency of EFA causes:
»Swelling of mitochondrial membrane
»Reduction in efficiency of oxidative
phosphorylation
»Increased heat production
• Synthesis of Eicosanoids:
– Eicosanoids are synthesized from arachidonic acid
by cyclooxygenase enzyme system & Lipoxygenase
pathway
– Ѡ-6 EFA, Linoleic acid serves as a precursor for
synthesis of arachidonic acid in animals including
human beings
30. Cont…
• Serum level of cholesterol & TAG
– Fats with high content of PUFA tends to lower
serum level of Cholesterol & TAG
• Role of EFA in fatty liver
– Deficiency of EFA produces fatty liver
• Effect on fibrinolytic activity
– An increase in fibrinolytic activity follows
ingestion of fats rich in EFA
• Effect on clotting time
– Prolongation of clotting time is noted in ingestion
of fats rich in EFA
• Role in vision:
– DHA (22:6∆4,7,10,13,16,19) is most abundant PUFA
present in retinal photoreceptor membranes
– Ѡ-3 EFA, α-Linolenic acid serves as a precursor
for synthesis of DHA
31. Cont…
• Role in skin:
– Ѡ-6 EFA, Linoleic acid covalently binds another
FA attached to cerebrosides in skin Unusual
lipid (acylglucosylceramide) is formed
» Helps to make skin impermeable to water
– This why?, Dietary deficiency of EFA associated with red,
scaly dermatitis
32. Cont…
• Unusual Fatty Acids
– Contain different structural features than
common fatty acid structures
• Trans double bond that is not common in natural fatty
acids
– E.g.,
» Eldaic acid, a trans form of oleic acid
33. Cont…
• Other functional groups
– E.g.,
» Cerebroic acid in nerve tissues & brain
contains hydroxyl group at position 2
» Lactobacillic acid in bacteria contains
cyclopropane group
34. Nomenclature of Fatty acids
– Fatty acids are abbreviated based on:
• Hydrocarbon chain length
• Number of double bonds
– Separated by a colon
» E.g.,
• 16-carbon saturated palmitic acid =>16:0
• 18-carbon oleic acid, with one double
bond=>18:1
– Positions of any double bonds are specified by
• Superscript numbers following ∆(delta)
– E.g.,
» 18-carbon fatty acid with one double bond b/n
C-9 & C-10 & another b/n C-12 & C-13 =>
18:2(∆9,12)
36. Physical properties of fatty acids
– Physical properties of fatty acids and compounds
that contain fatty acids can be determined by:
• Length of hydrocarbon chain
• Degree of unsaturation of hydrocarbon chain
– Solubility:
» The longer fatty acyl chain & fewer double
bonds, lower is solubility in water
» The shorter fatty acyl chain & more double
bonds, higher is solubility in water
– Melting points:
» The longer fatty acyl chain & fewer double
bonds, higher melting point of FAs
» The shorter fatty acyl chain & more double
bonds, lower melting point of FAs
37. Cont…
– Why Saturated FAs have higher melting point
when compared to unsaturated FAs?
• Reason:
– In fully saturated compounds, molecules can pack
together tightly
– In unsaturated fatty acids, a cis-double bond
forces a kink that prevents tight packing of
molecules
» Takes less thermal energy to disorder poorly
ordered arrays of unsaturated fatty acids, than
tightly ordered arrays of saturated FAs
38.
39. Cont…
Alcohols
• Lipid molecule contained alcohols:
– Glycerol
– Cholesterol
– Sphingosine
– Higher alcohols
• E.g. cetylalcohol, C16H33COOH (usually found in waxes)
Glycerol:
– Commonly called as “glycerin”
– Simplest trihydric (3-OH groups) alcohol
– Colourless oily fluid with a sweetish taste
– Miscible with water & alcohol in all proportions but is
almost insoluble in ether
40. Physiological Sources of Glycerol
• Endogenous source:
– Lipolysis of fats in adipose tissue
• Exogenous (Dietary) source:
– Approx. 22 % of glycerol directly absorbed to
portal blood from gut
Uses of Glycerol
• Industrial:
– Glycerol finds many uses in industry, as a result
of its solubility, its solvent action & its
absorbent nature
– Many pharmaceuticals & cosmetic preparations
have glycerol in their formulas
41. Cont…
• In medicine:
– Nitroglycerine is used as a vasodilator
– Glycerol therapy in cerebrovascular (CV)
diseases reduces cerebral oedema
• Physiological:
– In body, glycerol has definite nutritive value
– It can be converted to glucose/& glycogen,
process called as gluconeogenesis
42. Cont…
Steroids & Sterols
– Steroids:
• Are often found in association with fat
• Have similar cyclic nucleus resembling phenanthrene
(ring A, B and C) to which a cyclopentane ring (ring D)
is attached
• Cyclopentano perhydro-phenanthrene nucleus
– Methyl side chains at positions 10 & 13
(constituting carbon atoms 19 & 18 respectively)
– A side chain at position 17 is usual
• Steroids of biomedical importance
– Sterols
– Bile acids
– Adrenocortical hormones
– Gonadal hormones
– D vitamins
– Cardiac glycosides
44. Cont…
– Sterol:
• Steroid with one or more –OH groups & no carbonyl or
carboxyl groups
• Most important sterol in human body is cholesterol
Cholesterol:
• C27H45OH is its molecular formula
• Possesses “steroid nucleus” with:
– –OH group at C3
– Unsaturated double bond between C5 & C6
– Two –CH3 groups at C10 & C13
– Eight carbon side chain attached to C17
• Insoluble in water & slightly soluble in alcohol
• Soluble in ether, chloroform, hot alcohol, ethyl
acetate & vegetable oils
47. Cont…
Sources of cholesterol
– Exogenous (Dietary) source:
• Approximately 0.3 gm/day obtained from diets such as
butter, cream, milk, egg yolk, meat, etc.
– Endogenous Source:
• Approximately 1.0 gm/day of cholesterol synthesized in the
body from acetyl-CoA
Occurrence of cholesterol:
– It is widely present in body tissues
• 2 % in brain and nervous tissue
• 0.3 % in the liver
• 0.3 % in skin
• 0.2 % in intestinal mucosa
• >= 10 % in certain endocrine glands (adrenal cortex)
– Corpus luteum is also rich in cholesterol
48. Cont…
Forms of Cholesterol
– Exists in free & ester forms
• Cholesterol esters:
– Formed when FA esterifies with –OH group of
cholesterol at C3
– Also referred as bound form
– Various FAs esterifies with cholesterol
• 50% Linoleic acid
• 18% Oleic acid
• 11% Palmitic acid
• 5% Arachidonic acid
• 16% other FAs
49. Cont…
– Tissue distribution of two forms:
• Free form is equally distributed b/n plasma & red blood
cells
• Ester forms do not present in RBCs
• Free form predominates in brain & nervous tissue
• Ester forms predominates in adrenal cortex
– Biomedical importance of cholesterol
• As constituent of plasma membrane & plasma lipoproteins
• As precursor of steroid hormones, bile acids & pro-vitamin
D3
• Other Sterols of Biological Importance
– 7-Dehydrocholesterol
• Important sterol present in skin
• Only difference from cholesterol presence of 2nd double
bond, b/n C7 & C8
• Sources:
– In human, may be obtained partly by synthesis from
cholesterol in skin and/or intestinal wall
50.
51. Cont…
• Biomedical importance:
– In skin, UV rays change 7-dehydrocholesterol (pre-
cholecalciferol) to cholecalciferol (vitamin D3)
– 7-dehydrocholesterol is called as provitamin-D3
– This explains the value of sunshine in preventing
rickets, a disease produced from vitamin D
deficiency
– Ergosterol
• Plant sterol
• Isolated yeast & certain mushrooms
• Same as 7-dehydrocholesterol but, differs slightly in
its side chain
52. Cont…
• Biomedical importance:
– Moderate irradiation with UV rays changes
ergosterol to vitamin D2 (opening of ring B of
sterol)
» Ergosterol is called as Provitamin-D2
– Over irradiation with UV rays may produce toxic
products e.g., toxisterols & suprasterols
53.
54. Cont…
– Stigmasterol & Sitosterol
• Plant sterols
• Occur in higher plants
• No nutritional value for human beings
– Biomedical Importance
» Sitosterol appears to decrease intestinal
absorption of both exogenous & endogenous
cholesterol Lowering blood cholesterol level
– Coprosterol (Coprostanol)
• Trans form of cholesterol
• Occurs in faeces as result of reduction of cholesterol
by bacterial action
– Double bond b/n C5 &C6 is saturated due to
hydrogenation
– Rings A & B b/n C5 & 10 are unsaturated & trans-
configurated
55. Simple Lipids
– Triacylglycerols (TAGs)
• Also known as:
– Triglycerides
– Fats & oils
– Neutral fats & oils
• Constructed from 3-FAs & tri-hydric alcohol,
glycerol
• Non-polar, hydrophobic, water insoluble
molecules
• Can be simple or mixed based on type of
component fatty acids
56. Cont…
– Simple TAGs:
• All three component FAs are of same kinds
• Named after component FAs
– E.g.,
» Simple TAG of 16:0 =>Tripalmitin
» Simple TAG of 18:0=>Tristearin
» Simple TAG of 18:1=>Triolein
57. Cont…
– Mixed TAGs:
• Contain two or more d/t kinds of FAs
• Most naturally occurring TAGs
• Named after specific FAs & position of each FAs
– E.g.,
» Mixed TAGs of 18:0 at C-1, 18:2(∆9,12) at C-2 &
16:0 at C-3 =>1-stearoyl,2-linoleoyl,3-
palmitoyl glycerol
58. Cont…
– Types of TAGs
• Oils:
– TAGs with higher proportion of unsaturated FAs
– Liquid at room temperature
• Neutral Fats:
– TAGs with higher proportion of long chain
saturated FAs
– Solids at room temperature
• Butter:
– TAGs with higher proportion of short chain
saturated FAs
– Semi-solids at room temperature
59.
60. Physical properties of TAGs
– Melting point:
• Longer carbon chain of component FAs, higher melting
point TAGs
• Shorter carbon chain of component FAs, lower melting
point of TAGs
• More degree of un-saturation of component FAs, lower
melting point of TAGs
• Fewer degree of un-saturation of component FAs,
higher melting point of TAGs
– Oils have lower melting point than butter
– Butter has lower melting point than fats
– Specific gravity:
• Fats & oils are water insoluble with a specific gravity
of less than 1 Float on water
61. Cont…
– Emulsification:
• Vigorous shaking of neutral fats in water Unstable
emulsions (Emulsified fats)
• Stabilized by emulsifying agents:
– Gums
– Soaps
– Bile salts
– Phospholipids
• Important during fat digestion & absorption
– Increases surface area of fats for a better action
of digestive lipases
62. Chemical properties of fats & oils
– Hydrolysis/saponification:
• Simple lipids can be hydrolyzed by:
– Hot alkali
– Super heated steam
– Acid
– Lipases
– Esterases
• Hydrolysis products of hot alkali
– Glycerol
– Alkali salts of the free FAs (soaps)
» Such reaction Saponification
• Soaps:
– Facilitate emulsification of oils & grease (fats)
Increased solubility in water Removal of „dirt‟
from cloth or other materials
64. Cont…
– Hydrogenation & Margarine Industry:
• Hydrogenation, or hardening of fats & oils
– Carried out under high pressure at industrial scale
– Catalyzed by finely divided nickel or copper & heat
– Unsaturated FAs converted into saturated FAs
» E.g., Oleate Stearate
• Advantages:
– Hydrogenated products:
» More pleasant
» Less irritant to stomach
» Less liable to rancidity than original fats and oils
• Disadvantages:
» Reduces biological value of original fat or oil
• Due to loss of most of unsaturated bonds
» Facilitates cis- into trans-tranformation (toxic)
66. Cont…
– Oxidation:
• Atmospheric O2 oxidizes unsaturated FAs
– Epoxides
– Peroxides
– Endoperoxides
– Hydroxide derivatives
» Cause lipid deterioration
• Rancidity (in vitro)
• Lipid peroxidation (in vivo)
• Lipid peroxidation (in vivo)
– E.g., Oxidative damage of membranes via
deterioration of phospholipids
67. Cont…
– Rancidity:
• Physico-chemical change in natural properties of fats
or oils
– Unpleasant odor or taste or abnormal color
• Causes:
– Exposure to:
» Atmospheric oxygen
» Light
» Moisture
» Heat
» Bacterial contaminant
» Fungal contaminant
• Decomposes unsaturated FAs into toxic products
• Destroys associated fat-soluble vitamins
68. Cont…
– Types of Rancidity
• Hydrolytic rancidity:
– After bacterial lipase action (under high
temperature & moisture)
» Fats are hydrolyzed into volatile short-chain
free FAs Unpleasant odor
• Oxidative rancidity:
– After exposure of oils to atmospheric O2, light &
heat decomposition of oils into peroxides,
hydroxides, aldehydes, ketones & dicarboxylic
acids Unpleasant odor
• Ketonic rancidity:
– After fungal contamination of fats or oils in
presence of high moistureFat decomposition
mainly into ketones Unpleasant odor
69. Cont…
– Prevention of Rancidity
• Good storage conditions
• Addition of antioxidants
E.g.,
» Vitamin E
» Phenols
» Naphthols
» Tannins
» Hydroquinones
– Waxes:
• Esters of long-chain (C14 to C36) saturated &
unsaturated FAs with long chain (C16 to C30) alcohols
• Possess water-repellent properties & firm consistency
70. Biological importance of Waxes
– Chief storage form of metabolic fuel for marine
animals
– Waxes secreted by skin glands of certain
vertebrates
• Protection to hair & skin
• keep skin pliable, lubricated, and waterproof
– Waxes secreted by preen glands of waterfowl
birds
• Keep their feathers water-repellent
– Thick layer of waxes that coat shiny leaves of
many tropical plants
• Prevent excessive evaporation of water and protects
against parasites
71. Cont…
– Lanolin (from lamb‟s wool)
– Beeswax
– Carnauba wax (from palm tree)
– Wax extracted from sperm whales
• Widely used in the manufacture of lotions, ointments,
and polishes
72. Compound Lipids
– Also known as membrane lipids
– Membrane lipids are amphipathic:
• Hydrophobic end
• Hydrophilic end
– Hydrophobic interactions with each other &
hydrophilic interactions with water Direct
packing of membrane lipids into sheets
Membrane bilayers
• Acts as a barrier to the passage of polar molecules &
ions
– Two common membrane lipids:
• Phosphoglycerides
• Sphingolipids
73. Cont…
• Phosphoglycerides
– Also called glycerophospholipids
– Two FAs esterified to C-1 & C-2 of glycerol
» C16 or C18 saturated FAs at C-1
» C18 or C20 unsaturated FAs at C-2
– Highly polar group is attached to C-3 via
phosphodiester linkage
– Phosphatidic acid is a parent compound to all
phosphoglycerides
– Named as derivatives of phosphatidic acid
according to polar alcohol in head group
74. Saturated C16 or C18 FA
Unsaturated C16 – C20 FA
Derived from polar alcohol
Smallest = H
Least common in membranes
Phosphatidic acid
Phosphodiester
linkage
77. Cont…
– Biomedical Importance of Phosphoglycerides
(1) As major constituent of cellular & sub-cellular
organelle membranes
– Facilitates transport of substance across
membranes
– Cardiolipin
» Important component of inner mitochondrial
membrane
» Only human glycerophospholipid Antigenic
• E.g.,
• Used in serological diagnosis of syphilis &
autoimmune diseases
• Recognized by antibodies raised
against Treponema pallidum
Bacterium that causes syphylis
78. Cont…
(2) As Lipotropic agents
– Help in mobilization of fats from liver to
peripheral tissues
(3) Important for excretion of cholesterol into bile
(4) Important for digestion & absorption of neutral
lipids
(5) Important components of lung surfactants
– Prevent irreversible collapse of alveoli & neonatal
respiratory distress syndrome (RDS)
79. Cont…
• Lung surfactant complexes
– Type II alveolar cells in lungs produce lung
surfactant complexes:
» Dipalmitoyl-lecithin
» Sphingomyelin
» Apoprotein A, B, C, & D
– Lung surfactant Complexes:
» Anchored to surface of type I & II alveolar
cells
» Activates macrophages to kill pathogens
» Lowers alveolar surface tension Improves gas
exchange
81. Cont…
• Respiratory Distress Syndrome (RDS)
– Preterm babies:
» Deficiency of lung surfactant complexes is
caused due to immaturity of lung alveoli
» Suffer difficulty of breathing at time of
delivery & during early infancy Respiratory
distress syndrome (RDS)
– Rx:
» Glucocorticoids
• Promote early differentiation of lung cells
• Increase synthesis of lung surfactant
complexes
• Small dose of glucocorticoids is injected to
mothers liable to give a preterm baby
82. Cont…
(6) Play important role in signal transduction across
cell membrane
– E.g.,
» Phosphatidyl inositols (Lipositols)
• Major phosphoglycerides in inner leaflet of
cell membrane
• Plays major role as second messengers during
signal transduction for certain hormones
• For signal transduction:
• Lipositols further phosphorylated at C4 &
C5 of inositol by receptor-mediated
activation of its kinase Phosphatidyl-
inositol-4,5-diphosphate On
hydrolysis by phospholipase C DAG &
IP3 Both act as mediators of hormone
action
• Major effect is release of calcium
from intracellular stores
O
H
H
OH
OH
H
OH
H
OH
OH
H H
1
3
2
5
4
6
CH2
CH
O
CH2
CH2 C
O
R2
P
O
O
OH
-Phosphatidylinositol(Inositide)
O
CH2 C
O
R1
myo-Inositol
83. Cont…
(7) As source of PUFAs for synthesis of eicosanoids
– Physiologically, body phospholipase A2 releases
PUFAs from membrane lipids for eicosanoid
synthesis
84. Clinical comments related to Phosphoglycerides
•Snake venoms
– Hydrolysis of one of ester bonds in
Lecithin/cephalin Lysolecithin/Lysocephalin
» Hemolytic, i.e., causes hemolysis of RBCs
– Venoms of snakes, scorpion, poisonous spiders &
stinging insects contain phospholiphases
(Lecithinase / Cephalinase)
» Act on lecithin/cephalin Lysolecithin/
Lysocephalin
• This explains toxic effect of venoms &
bites
85. Cont…
• Cephalins & Apoptosis
– Apoptosis „Programmed cell death‟
» Regular mechanism by which body eliminates
diseased or damaged cells
– Serine-cephalins
» Located primarily in inner leaflet of cell
membrane
» During Apoptosis:
• Exposed in outer leaflet of cell membrane
Diagnostic marker for early apoptosis
86. Cont…
– Ether lipids
» Phosphoglycerides with ether-linked FAs
• FA at C-1 of glycerol Ether (R-O-R) -
linked
• FA at C-2 of glycerol Ester -linked
» Two types:
• Alkyl ether lipids
• Ether-linked chain saturated
• E.g.,
• Platelet activating factor (PAF)
• Synthesized /released by variety of
cell types
• Binds to surface receptors
• Activates inflammatory cells
87. Cont…
• Mediates hypersensitivity, acute
inflammatory, & anaphylactic reactions
• E.g.,
• Neutrophils cause platelets to
aggregate & degranulate, & alveolar
macrophages to generate
superoxide radicals
– Plasmalogens
» Ether-linked chain unsaturated in b/n C-1 & C-2
» Heart tissue is uniquely enriched in ether lipids
89. Cont…
– Sphingolipids
• Another large class of membrane lipids
• Like phosphoglycerides
– Polar head group
– Non-polar tails
• Unlike phosphoglycerides
– No glycerol Sphingosine
– No two FAs Only one long-chain FA
– Polar head group joined not phosphodiester lonkage
only Glycosidic linkage in some cases &
Phosphodiester in others
90. Cont…
• C-1, C-2 & C-3 of sphingosine analogous to C-1, C-2 &
C-3 of glycerol in phosphoglycerides
• FA amide linked to -NH2 on C-2 Ceramide
– Parent compound of all sphingolipids
• FA linked:
– Saturated or monounsaturated (C-16, 18, 22, or 24)
93. Cont…
– Sphingomyelins:
• Also called sphingophospholipids
• Choline or ethanolamine phosphodiester linked to C-1
of sphingosine
• Contained in myelin sheath of axons =>
“sphingomyelins”
94. Clinical comment related to sphingomyelin
–Niemann-Pick disease
»Rare hereditary fatal disease that occurs in
infants
»Caused by hereditary deficiency of lysosomal
enzyme, sphingomyelinase
•Involved in regular turnover of sphingomyelins
»Sphingomyelinase deficiency Abnormal
accumulation of sphingomyelins in liver, spleen &
brain tissues
»Clinically presentation:
•Enlargement of abdomen, liver & spleen
•Progressive mental retardation
95. Cont…
– Glycosphingolipids:
• One or more sugars are glycosidic linked to C-1 of
sphingosine
• Occur largely in outer face of plasma membranes
• Not charged at pH 7 Neutral glycolipids
– Cerebrosides:
» Single sugar linked to ceramide
• Plasma membranes of neural tissue
Galactose
• Plasma membranes of non-neural tissues
Glucose
– Globosides:
» Two or more sugars linked to ceramide
• Usually D-glucose, D-galactose, or N-acetyl-
D-galactosamine
96. Cont…
• Gangliosides:
– Most complex sphingolipids
– Contain:
» Oligosaccharides as their polar head groups
» One or more N-acetylneuraminic acid (Neu5Ac),
(sialic acid) at oligosaccharide termini
– Negatively charged at pH 7 (# globosides)
» Due to presence of sialic acid
– Subclasses (based on number of sialic acid):
» GM (M=mono-) series One sialic acid
» GD (D=di-) seriesTwo sialic acids
» GT seriesThree sialic acids
» GQ series Four sialic acids
98. Cont…
• Determinants of blood groups:
• Carbohydrate moieties of certain gangliosides
–Define human blood groups (A, B, AB & O)
–Determine type of blood that individuals can
safely receive in blood transfusions
