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Dr. Smita Pakhmode
LIPID CHEMISTRY
Dr. Smita Pakhmode,
Associate Professor , Biochemistry, NKP SIMS & RC. Nagpur
Dr. Smita Pakhmode
Com
pete
ncy
No
Competency Domain Core
B14.
4
Describe and discuss main classes of
lipids (Essential/non-essential fatty acids,
cholesterol and hormonal steroids,
triglycerides, major phospholipids and
sphingolipids) relevant to human system
and their major functions.
K/KH Y
Dr. Smita Pakhmode
LIPID CHEMISTRY
Lipid chemistry includes-
Definition & Distribution of lipids in the body
Describe & Discuss main classes of lipids
( Essential, non essential fatty acid, cholesterol,
& Hormonal steroid, TAG, phospholipids &
Spingophospholipids,) relevant to human system
and their functions.
Describe structure & functions of lipoproteins
Describe therapeutic uses of PGS & inhibitors
of eicosanoid system.
Dr. Smita Pakhmode
What are lipids:
Heterogeneous group of substances:
1.Relatively insoluble in water
2. Freely soluble in non polar solvents
(ether, benzene, chloroform, acetone)
3. Actually or potentially related to fatty
acid. ( as esters of fatty acid with
alcohol).
4. Utilized in metabolism by living
cells.
Dr. Smita Pakhmode
 CH2OH CH2OH
CHOH + HOOCR CH00CR
Ester OF FA
CH2 OH CH2 OH
 Glycerol fatty acid
Monoglyceride
•Definition- Lipids are heterogeneous groups of
compounds which are relatively insoluble in water &
freely soluble in organic solvents.
• Chemically lipids are esters of fatty acids with alcohol or
substances capable of forming esters with fatty acids.
Dr. Smita Pakhmode
Occurrence of fats/ lipids in our body
Fats are present-
Beneath the skin – subcutaneous fat
 Around the internal organs – mesenteric fats
Nervous tissues and cell membrane -
Cholesterol, Phospholipids, Glycolipids.
Blood – Lipoproteins, Cholesterol.
Storage form of fats ‘Adipose tissue’.
Dr. Smita Pakhmode
Biomedical importance of lipids
( functions of lipids)
Storage form of energy.
Insulating effect & padding
give shape & contour to the body.
Structural component of Biomembrane.
necessary for cellular integrity.
Source of Essential Fatty Acids (EFA) & fat
soluble vitamins.
Dr. Smita Pakhmode
Biomedical importance:
Metabolic regulators- steroid hormones & PG
 second messenger- Phosphatidyl inositol
blood clotting- The phosphatides of blood platelets
As carriers – Lipoproteins
• Constituent of nervous system
• Components of inner mito memb ( in etc ).
• Acts as a surfactant, detergent & emulsifying agent.
Add taste &palatability to food
Dr. Smita Pakhmode
• INVOLVED WITH DISEASES LIKE
ATHEROSCLEROSIS, FATTY LIVER,
OBESITY
Clinical Applications of Lipids
Excessive fat deposit leads to Obesity.
Abnormality Chol. & LP leads
atherosclerosis & IHD
Diabetes Mellitus leads to abnormal fat
metabolism to Ketosis
Lipdome & Lipidomics
Dr. Smita Pakhmode
Classification of lipids:
four major types of lipids –
1)Simple lipids
2)Compound lipids
3)Derived lipids
4)Lipids complexed with other compounds.
Dr. Smita Pakhmode
1) Simple lipids-
b) waxes- esters of higher FA with alcohol
other than glycerol (higher alcohol e.g. Cetyl
alcohol)
In human body common waxes are esters of
cholesterol.
1. cholesterol ester
2. vitamin A ester
3. vitamin D ester
Esters of fatty acids with alcohols
Two types-
a) Fats and oils: esters of FA with alcohol, glycerol
Oils - liquid at room temp-
Dr. Smita Pakhmode
2) Compound/ Complex lipids –
Definition- Esters of FA with alcohol
containing one or more additional group
like phosphates, carbohydrates, nitrogen
base, proteins etc.
Phosphorylated lipids: Phosholipids
FA + Alcohol+N2base+ Phosphoric acid
1. Glycerophospholipids:
Lecithin, Cephalin, Plasmalogen, Cardiolipin etc.
2. Spingophosholipids:
Sphingomylein
Non Phosphorylated Lipids
• Glycolipids: FA + Sphingosin+N2base+ Carbohydrate
Cerebrosides :Ceramide Monohexoside
Gangliosides: Ceramide oligosaccharides
Globosides: Ceramide oligosaccharides + NANA
• Sulfolipid:
Sulfated Cerebroside, Sulfated Ganglioside,
sulfated globoside
Dr. Smita Pakhmode
Dr. Smita Pakhmode
3)Derived lipids
Possess the properties of lipids.
eg: Fatty acids, Glycerol, Cholesterol, Vit A,
Vit D, Turpents, Leukotriens, and prostaglandins
Derived Lipids
simple lipids
breakdown compound lipids
Dr. Smita Pakhmode
4. Lipids complexed with other
compounds:
Lipoproteins:
VLDL, , IDL, LDL, HDL & Free fatty
acids.
Proteolipids:
protein covalently linked to lipid
molecules, which can be fatty acids or
sterols.
Ex:, annexins, lipocortin, calpactin, endo-
nexin, chromobindin, and anchorin.
Dr. Smita Pakhmode
Miscellaneous Lipids
Squalenes
Carotenoids
Vitamin E
Vitamin K
Aliphatic hydrocarbons in bee’s wax, plant
wax
Chemically do not follow the definition of lipids but
possess characteristics of lipids.
Dr. Smita Pakhmode
Neutral lipids
Lipids which are uncharged
eg: MAG, DAG, TAG.
Cholesterol& chol. esters
Dr. Smita Pakhmode
Fatty acids (R-CH2-COOH)
Carboxylic acid derivatives of long chain
hydrocarbons.
derived lipid
 Simplest form, found in abundance.
 majority are in esterified form
-
(CH2)n
CH3 COOH
n is almost always even
n = 0 : CH3COOHn = 1 : propionic acid
-anoic acid: Saturated fatty acid
-enoic acid: Unsaturated acid
Dr. Smita Pakhmode
SATURATED FATTY ACIDS
General formula: CH3 –(CH2) n-COOH
 Acetic acid CH3COOH C2 Vinegar
 Propionic acid CH3CH2COOH C3 Int. of metabolism
 Butyric acid CH3(CH2)2COOH C4
butter
 Caproic acid CH3(CH2)4COOH C6
 Lauric acid CH3(CH2)10COOH C12
 coconut oil
 Myristic acid CH3(CH2)12COOH C14
 Palmitic acid CH3(CH2)14COOH C16 Body fat
 Stearic acid CH3(CH2)16COOH C18 plant EICOSA
 Arachidic acid CH3(CH2)18 COOH C20 Peanut EICOSA
Human body fat : 50% Oleic Aicid, 25%Palmitic Acid, 10% Linoleic acid & 5%
Stearic acid
Dr. Smita Pakhmode
Unsaturated fatty acids
Monoenoic acid (monounsaturated)
Oleic acid
H3C
HOOC
Double bond is always
cis in natural fatty acids.
This lowers the melting
point due to “kink” in
the chain
Oleic acid 18:1; 9
Dr. Smita Pakhmode
Unsaturated fatty acids
Polyenoic acid (polyunsaturated)
Arachidonic acid
COOH
CH3
Arachidonic Acid 20:4; 5,8,11,14.
Dr. Smita Pakhmode
Unsaturated Fatty Acids
Isomerism in unsaturated fatty acids:
Cis Trans
Less stable more stable
L,U shaped Straight chain
Naturally occurring Fast food & during
FA metabolism
Helps in compact Injurious to health
Cell membrane
Monounsaturated
Polyunsaturated
Dr. Smita Pakhmode
Fatty Acids- Numbering System
Two systems for numbering carbon atoms
of fatty acids –
1)Delta system – numbering starts from
carboxylic end.
2) Omega system – numbering starts
from farthest carbon atom of FA.
Dr. Smita Pakhmode
CH3CH2-CH2CH2 CH2 CH2 CH2 CH2CH2CH2CH2CH2 CH2 CH2CH2-COOH
• Palmitic acid 16:0
•
omega endω α end
CH3CH2CH2CH2-CH2CH2 =CH2 CH2CH2 =CH2CH2CH2CH2CH2 CH2 CH2CH2-COOH
• Linoleic acid 18: 2; 9,12,
• ω6 series
CH3CH2CH2=CH2-CH2CH2 =CH2 CH2CH2 =CH2CH2CH2CH2CH2 CH2 CH2CH2-COOH
Linolenic acid 18: 3; 9,12,15
ω3 series
Biomedical Significance of ω3: Pleiotropic effects
Positve role in infant brain development,
Prevents Cancer, CVS,& mental illnesses like depression, ADHAD &
dementia. Inflammation ,Pl aggregation, HT & Hyperlipidemia.
Dr. Smita Pakhmode
Classification
3) Nutritional classification
Essential fatty acid (EFA) & Non essential fatty
acids
1) According to structure:
Even chain(Naturally occurring)/ Odd chain
(Microbial cell wall & Milk)
Saturated / unsaturated
Cyclic/hydroxy/eicosanoids fatty acids (FA)
2)According to chain length:
short chain FA: 2-6 carbon atoms
medium chain FA: 8 –14 carbon atoms
long chain FA: 16 – 24 carbon atoms
Very long chain FA: > 24 carbon atoms
Dr. Smita Pakhmode
Composition of FA in dietary fats
Mostly present in triacyl glycerol
Animal sources- butter, lard, ghee, fish oil. -
rich in saturated FA (40-50%)
Plant sources - beans, seeds, leaves.
- rich in unsaturated FA(80-90%)
Simple
Complex
Dr. Smita Pakhmode
How to choose oil:
 High PUFA content.
Cis FA prefered.
 High ω3 /ω6 ratio.
SFA:MFA:PUFA:- 1:1:1
Oil with high:
 SFA: Palm, coconut & Ghee.
MUFA: Groundnut, Mustard, Sesame oil.
PUFA: Sunflower, Safflower, Soyabean,
Dr. Smita Pakhmode
Fatty acids Classification
Saturated
Acetic acid
Lignoceric
acid
Sources
Butter,
Coconut oil,
Animal fat,
Arachis oil
Unsaturated
Oleic acid
Linoleic acid
Linolenic acid
Arachidonic acid
Sources
All veg oils
EFA
Eicosanoids
20C cyclic PUFA
Prostaglandins,
Leukotrienes,
Thromboxanes.
Cyclic FA
1.Hydrocarpic
acid
2.Chaulmoogric
acid
Sources
Chaulmoogra
oil
Use-
Treatment of
leprosy
Hydroxy FA
1.Ricinoleic Acid
2.Dihydroxy
stearic acid
Sources
Caster oil
3.Cerebronic acid
in brain
1
2
3
4
5
Dr. Smita Pakhmode
Essential Fatty Acids(PUFA)
Essential Fatty acids are those which are not
synthesized in the body& are essential in the diet.
Lack Enzyme which introduces double bond beyond 9-10
- Linoleic acid(18:2 ;9,12)
Sources: Corn oil, Peanut oil, Cottonseed oil,Soybean oil
– Linolenic acid ( 18:3; 9,12,15)
Sources: Walnuts, Wheat germ oil, Flaxeed oil, Fish liver
oils/Fish eggs, Human Milk, Seafood/Fatty fish
-Arachidonic acid- (20:4; 5, 8,11,14)
Sources: plant oils
Dr. Smita Pakhmode
Conditionally Essential Fatty acid:
Docohexanoic Acid( DHA, ω3 ;22:6)
Linoleic Acid DHA
Preterm Infant
Imp. For
developing
brain
Infant
Nutrient
formulas
Fish oil
EPA & DHA
Dr. Smita Pakhmode
Functions of EFA/PUFA
1. Formation of healthy cell membranes
2. Proper development and functioning of the Brain, Eye,
Nervous system.
3.Necessary for lipoprotein synthesis
4. Transport & esterification of serum cholesterol.
5.Prevent fatty liver.
6.Production of hormone-like substances -- Eicosanoids
(Thromboxanes, Leukotrienes, Prostaglandins )
7. Regulation of
blood pressure, blood viscosity, vasoconstriction,
immune and inflammatory responses.
8. Role in reproduction.
9. Linolenic acid: required for optimal vision.
Dr. Smita Pakhmode
phrynoderma / toad skin.
Acanthosis & Hyperkeratosis at
extensor aspect.
Found in 1.Infants on
formula feeds,
2. IV nutrition
Dr. Smita Pakhmode
phrynoderma / toad skin.
 Deficiency symptoms of EFA
 Acanthosis & Hyperkeratosis at extensor aspect.
 loss of hair.
 Poor wound healing.
 Cessation of growth.
 Degenerative changes in arterial wall.
 May lead fatty liver.
Impaired LP
Meta.
Dr. Smita Pakhmode
Triacylglycerols:
Function: storage of energy in compact form and cushioning
CH2OOCR
|
CHOH
|
CH2 OH
CH2OOCR
|
CHOOCR
|
CH2 OH
CH2OOCR
|
CHOOCR
|
CH2OOCR
DAG TAG
simple
Mixed.
Esters of trihydric alcohol Glycerol with Fatty acid.
Neutral fat
1
2
3
Dr. Smita Pakhmode
Properties of Lipids:
(TAG/ FA)
 Oil --- Liquid, High Unsat FA & SCFA, Plant origin.
 Fats --- Solid, High Sat. FA & LCFA, Animal origin.
 MP increases with chain length and decreases with
unsaturation
 when shaken with water, oils tend to emulsify.
 pure fats and oils colorless and odourless
 (color and odour autooxidation )
-
Physical :-
Dr. Smita Pakhmode
37
Chemical :-
1] HYDROLYSIS (Lipolysis) – Sequential hydrolysis of TAG
TAG DAG. MAG. 3FA + Glycerol
Eg : by Lipases in digestion of fat in GIT
Fat mobilization from adipose tissue
2] SAPONIFICATION
Triglyceride + 3NaOH Glycerol +3 R-COONa
“soap”
Hydrolysis of TAG by alkali to produce glycerol & soap
Dr. Smita Pakhmode
38
Hydrogenation
glyceryl tripalmitoleate
(tripalmitolean)
glyceryl tripalmitate
(tripalmitin)
O
(CH2)14CH3
C
O
(CH2)14CH3
C
O
(CH2)14CH3
C
O
O
O
CH2
CH2
CH
CH(CH2)7CH3
(CH2)5CH
O
C
CH(CH2)7CH3
(CH2)5CH
O
C
CH(CH2)7CH3
(CH2)5CH
O
C
O
O
O
CH2
CH2
CH
+3H2
Dr. Smita Pakhmode
Hydrogenation:
 conversion of unsaturated fats to saturated
( Vanaspati from oil )
 Makes oil/fat more stable to oxygen and
temperature variation.
 increase shelf life.
Halogenation:
Addition of two halogen atoms across double bonds
to form Halide derivatives.
Oleic acid + I2 Diidooleic acid
No. of Halogen atoms directly proportional to ͠degree of saturation
Dr. Smita Pakhmode
RANCIDITY –
Unpleasant taste & odour due to exposure to heat, light,
moisture.
unsuitable for consumption.
Types:
Hydrolytic: By bact. Enzymes.
Oxidative
Oxygen
Fats/ Oil Ketones/ Aldehyde/ Dicarboxylic
acid
ANTIOXIDANTS in oils :- Vit E, Hydroquinones, gallic acid, α –
napthol.
Food preservatives
Propyl Gallate, Butylated hydroxyanisol ( BHA ), BHT ( toluene)
Dr. Smita Pakhmode
Lipid peroxidation
a non-enzymatic reaction catalyzed by
oxygen
may occur in tissues or in foods (spoilage).
Unsaturated FA Peroxides
+
free radicals
Oxidation of Protein/ DNA
(Aging & Cancer)
O2, H2O
Autooxidatio
Dr. Smita Pakhmode
Antioxidants
Substances that prevent auto oxidation in
body or in stored fat ( Rancidity) are
antioxidants.
Antioxidants –
Body – Vitamin E , A , C , Uric acid,
Superoxide Dismutase, Glutathione
Peroxidase.
Preservative- Gallic acid, Phenols
Dr. Smita Pakhmode
Iodine No. –gms (No.) of iodine absorbed by 100 gm
of fat or oil.
Higher iodine no………… more is the degree of unsat.
Helps in detection of adulteration of given oil.
REICHERT MEISSL NO – Soluble volatile FA
no. of ml of 0.1 N KOH req. to neutralize soluble
volatile FA distilled from 5g of fat.
(RM Of Butter: 25-30/ Oil : < 1)
Useful in testing the purity of butter.
Butter has high RM No. helps chemists identify
butter substitutes.
Tests to check purity of Fat
Dr. Smita Pakhmode
Saponification number
 Defined as the milligrams of KOH needed to
hydrolyse 1 Gm of fat or oil.
 Measure of avg. molecular size & SC FA content.
 If mol wt is more- less saponification no.
Human fat- 195-200.
Butter- 230-240
Cocconut oil– 250- 260
ACID NUMBER – mg of KOH required to completely
neutralize FFA in 1g of fat or oil.
Bacterial Or Chemical contamination forms FFA.
Higher the no. more rancid is the oil.
Dr. Smita Pakhmode
Compound lipids:
Dr. Smita Pakhmode
Complex lipids
Glycerophospholipids
Composition- FA,
N-base, Phosphate
group, Glycerol.
(alcohol)
Sphingophospholipids
Composition- FA,N-
base
Phosphate group,
Sphingosine (alcohol)
1. Phospholipids – Two Types
Dr. Smita Pakhmode
Phosphatidic Acid
In phosphatidate:
 fatty acids are esterified to hydroxyls on
C1(sat.) & C2(unsat.) the C3 hydroxyl is
esterified to Pi.
O P O
O
O
H2C
CH
H2C
O
C
R1
O O C
O
R2
phosphatidate
R1
2
Dr. Smita Pakhmode
48
Glycerophospholipids
Glycerol
PO4 N-Base
Fatty acid
Fatty acid
(phosphoglycerides), are common constituents of cellular membranes
polar
non-polar
"kink" due to
double bond
O P O
O
O
H2C
CH
H2C
O
C
R1
O O C
O
R2
X
glycerophospholipid
Each glycerophospholipid
includes
 a polar region:
glycerol, carbonyl O
of fatty acids, Pi, & the
polar head group (X)
 non-polar hydrocarbon
tails of fatty acids (R1, R2).
Dr. Smita Pakhmode
1)Lecithin (Phosphatidyl Choline)
•abundant in cell memb, brain and nerve tissues.
•found in egg yolk, wheat germ, and yeast
d
Functions:
Bodys cholin reserve.
Dissove chol . In bile
Digestion & absorption of lipids
.
Esterification of free cholesterol.
Forms lipoprotein complexes.
Provide Arachidonic acid.
Dr. Smita Pakhmode
Dipalmitoyl lecithin
 Surfactant Respiratory Distress syndrome:
Common in premature infant.
Def. of DPL
Lecithin /spingomylein ratio:
To asses the maturity in IU life
Dr. Smita Pakhmode
Lysolecithin
Obtained by removal of one fatty acid
from Lecithin.(c2)
By enzymes Phospholipase A2 & LCAT
H
Acts as a detergent & haemolytic agents.
Present in Viper snake venom
Dr. Smita Pakhmode
PHOSPHOLIPASE ACTION
PL A1
PL A2
PL C PL D
PLA1:- Acyl Glycerphosphoryl choline +
FFA.
PLA2 :- Lysolecithin
PL C:- 1,2DAG + Phosphoryl choline.
PL D:- Phospatidic acid + Choline.
Dr. Smita Pakhmode
54
2)Cephalin (Phosphatidyl Ethanolamine)
sur
Surfactant Blood clotting
Component of cell membrane.
Important in Blood clotting.
Dr. Smita Pakhmode
3)Phosphatidyl inositol
Commonly utilized in cellular signaling (second messenger)
Inositol
Dr. Smita Pakhmode
4)Phosphatidyl Serine
Inositol
O- serine
Present in nervous tissues & brain
Dr. Smita Pakhmode
Plasmalogen
5)Plasmalogen
Possess an ether linkage
at the C-1 position
Ethanolamine
6)PAF
potent mediator in
inflammation
allergic response
Dr. Smita Pakhmode
6)Cardiolipin
antigenic properties used in serologic test for
syphilis (Wasserman test).
Found in Mitochondrial membrane.
↓ levels: Heart failure, Hypothyroidism & Myopathies.
Phosphatidic acid Phosphatidic
acid
Glycerol
Joined by Glycerol bridge
Dr. Smita Pakhmode
Spingosine acts as a backbone
Fatty acids are attached with amide linkage: Ceramide
Phosphate group attached as ester bond wth alchohol and
cholin
Sphingophospholipids
Sphingophospholipids
•Found abundantly in brain,nervous tissue, RBC
membrane.
•Regulate protein kinase & phosphatase.
•It is hydrolysed by Sphingomyelinase.
• Inherited disorder - Niemann Pick’s disease
Sphingomyelin
AR, Hepatosplenomegaly & Mental Retardation
80% die within @ years
Lecithin /spingomylein ratio:
To asses the maturity in IU life
Dr. Smita Pakhmode
 Ceramide: The amino group of sphingosine can form an
amide bond with a fatty acid carboxyl.
 Devoid of Sugar.
 Importance:
 Second messenger in regulating cell cycle, cell differentiation
and apoptosis.
 Regulate skin water permiability.
Anti phospholipid antibodies:
Antibodies against membrane lipids, Cardiolipin
Found in autoimmune disorders & Thromboitic
episodes
in pregnancy : Miscarriage, eclampsia, preterm labour
Dr. Smita Pakhmode
Functions of phospholipids
 Lecithin –
 Cephalins –
 Phophatidyl inositol –
 Phophatidyl serine –
 Plasmalogen&
 PAF.
 Cardiolipins –
 Lysolecithin –
 Surfactant
 Blood clotting
 Second messenger
 in brain, nervous tissue
 Inflammation,allergies
 Antigenic properties
 Detergent & Haemolytic
Dr. Smita Pakhmode
- Acts as a lipotropic factor.
Synthesis of Lipoprotein
solublization & transport of cholesterol
- ABSORBTION & TRANSPORT OF FAT
- COMPONENTS OF BILE
- PG SYNTHESIS FROM ARAC. ACID
OTHER FUNCTIONS
Regulates membrane permeability
ETC ( maintaining conformation of components of etc.)
Dr. Smita Pakhmode
GLYCOLIPIDS ( NON PHOSPHORYLATED LIPID)
Seen widely in nervous tissue.
Ceramide=
Sphingosine(Amino alcohol)+ Cerebronic acid (VLCFA)
Glycolipids= CARBOHYDRATE + CERAMIDE
Types of glycolipids:
cerebrosides, Globosides
gangliosides,
Dr. Smita Pakhmode
GLYCOLIPIDS
 Cerebrosides
 Ceramide + sugar molecule
• Galactocerebroside – in neuronal membranes
• Glucocerebrosides – non neuronal tissues.
Gauchers disease:
AR, Enzyme defect : Glucocerebrosidase.
3 Types: Adult, infantile, Juvenile.
Hepatosplenomegaly, Anaemia, Erosion of bones.
Bleeding tendency & Sec. Infections.
In Infants: Growth & Mental retardation.
Dr. Smita Pakhmode
Gangliosides
 Have a more complex oligosaccharide attached
Ceramide + oligosaccharides with at least one mole. Of
NANA.
 Ceramide – Glu—Gal— NANA
 Present in gray matter in high concentration.
 Biological functions: cell-cell recognition; receptors for
hormones.
 common gangliosides:
 GM1, GM2,, GD1a, GD1b, GT1a, GT1b,
 Tay sachs Disease:
 GM2 accumulates in neurons
Dr. Smita Pakhmode
GLYCOLIPIDS
 Sulfatides or sulfogalactocerebrosides( also
referred as sulpholipids)
A sulfuric acid ester of galactocerebroside
 Globosides: ceramide oligosaccharides
Lactosylceramide
• 2 sugars ( eg. lactose)
Dr. Smita Pakhmode
Lipid storage diseases(Sphigolipidoses)
Disease Deficient enzyme Major storage
compound
1.Niemann-Pick Sphingomyelinase Sphingomyelins
2.Goucher’s β-Glucosidase Cerebroside(glucose
)
3.Krabb’s β-Galactosidase Cerebroside(galacto
se)
4.Tay-Sach’s Hexosaminidase A Gangliosides
5.Fabry’s α Galactosidase Ceramides
Dr. Smita Pakhmode
Compound lipids:
Dr. Smita Pakhmode
Amphipathic lipids
 Molecules containing both hydrophilic &
hydrophobic groups.
 Examples:
 1. Fatty Acids
 2. Phospholipids
 3Bile salts
 4. Cholesterol
Dr. Smita Pakhmode
Cholesterol is largely
hydrophobic.
But it has one polar
group, a hydroxyl,
making it amphipathic.
Cholesterol
HO
Cholesterol, an
important
constituent of cell
membranes, has a
rigid ring system and
a short branched
hydrocarbon tail.
cholesterol
PDB 1N83
Dr. Smita Pakhmode
Stable & permanent molecular arrangements:
 Micelle: E.g., a spherical micelle
 A bilayer: E.g. Membrane lipids
 Liposomes:
 Emulsions
Bilayer Spherical Micelle
Amphipathic lipids
--complexes in which polar
regions are in contact with
water and hydrophobic
regions away from water.
Dr. Smita Pakhmode
Liposome:
 Sphere shaped vesicle consisting of one or more lipid
bilayer enclosing water.
 When Phospho lipids are sonicated with cholesterol,
they are dispersed in the water to form vesicle or
liposomes.
 Intermidiate aqueous layer in lipid bilayer.
Significance:
 Carrier of drugs to target tissue
 Used for gene transfer
 Used in cancer chemotherapy.
 Formation of vaccine
 T/t of ophthalmic disorders.
Second
generation
liposomes
Dr. Smita Pakhmode
Case studies:1
 A 24 years women has put on weight after a child birth
was advised by physician to reduce her calorie intake.
Being impatient, she stopped consuming fats and oils.
Though she lost excess weight . After a few months ,she
developed a skin lesions on posterior and lateral aspects
and her limbs and buttocks.
 1.Identify the disease.
 2What is its biochemical basis?
 3Suggest the treatment.
Dr. Smita Pakhmode
Case studies:2
A preterm infant born to malnourished
mother became dyspnoic ( difficulty in
breathing). He was immidiately put on
respiratory aids and necessary treatment
was instituted.
Diagnose the disease condition.
What is biochemical basis of disease?
What is line of treatment?
Dr. Smita Pakhmode
Structure of Lipoprotein
Dr. Smita Pakhmode
77
Lipoproteins
 Lipids complexed with other compounds
 Def- Soluble molecular complexes of lipid with specific protein
called apolipoprotein.
 Function:1Transport of lipids in plasma .
 2. Deliver lipids to tissue
Lipoprotein classes:
1)chylomicrons:
Dietary TAG from small intestine----------------------Tissue
2) very low density lipoproteins (VLDL)
Endogeneous TAG from Liver--------------------tissue
3) low density lipoproteins (LDL)
Chol from Liver ------------------ Tissue
4) high density lipoproteins (HDL)
Chol from Tissue------------------ Liver
5) FFA-Albumin
Dr. Smita Pakhmode
Chylomicron
LDL(Beta)
VLDL(Pre Beta)
FFA
HDL( Alpha)
Cathod (--)
Anode (+)
Point of origin
Electrophoretic separation
of Lipoproteins
Dr. Smita Pakhmode
Fraction Source Apoprotein Protein
%
Total
Lipid %
TG PL Chol
Chylomicro
n
Intestine B48, CII, E 1-2 98-99 90 04 06
VLDL Liver &
Intestine
B100,CII, E 7-10 90-93 50 19 19
LDL Blood B 100 20 80 11 24 45
HDL Liver A, CII, E 33 67 05 30 18
Types of Lipoproteins •differ in density, composition, and function.
Dr. Smita Pakhmode
80
Steroid Nucleus
A steroid nucleus consists of
CYCLOPENTANOPERHYDROPHENANTHRENE RING
• 3 cyclohexane rings.
• 1 cyclopentane ring.
• no fatty acids.
steroid nucleus
Dr. Smita Pakhmode
WIDELY DISTRIBUTED :-
Plant – ergosterol & sitosterol
Animal – Cholecalciferol, sex hormones, ACTH, Bile acid,
cardiac glycosides.
( mainly in adrenal Cortex, brain, corpus luteum, testes, kid,
liver )
Dr. Smita Pakhmode
82
Cholesterol
• most abundant steroid
• has methyl CH3- groups, alkyl chain, and -
OH attached to the steroid nucleus.
C27H46OH
H3
H3
H3
H3
H3
Dr. Smita Pakhmode
Free(30%)
Occurence of cholesterol
Total(70%)
 Distribution:
 Widely present in human tissue.
 Present in brain & nervous tissue, liver , skin, endocrine
glands, bile, blood.
 Source:
 Meat, milk, eggs, Denovosynthesis & from acetyl CoA.
 Stored as:
 cholesterol esters- LDL, HDL
 Excretion:
 Bile(60%), intestine & faeces.
 Normal range: 150-250mg%.
Dr. Smita Pakhmode
84
Cholesterol in the Body
.Serum cholesterol
• > 200mg/dl is
considered to be high.
• Blocks arteries when
high levels, form
plaque.
An artery clogged
by cholesterol
plaque
A normal, open artery.
Dr. Smita Pakhmode
Importance of Cholesterol
Essential component of cell membrane
Precursor of adrenocortical
hormones- cortisol, aldosterone
Precursor of sex hormones
Estrogen, testosterone
Precursor to bile acids
Precursor of Vitamin D
Insulator of nervous system
Found only in animal products
Dr. Smita Pakhmode
Derived lipid
• Unsaturated hydroxy acids, consisting of a 20 carbon
skeleton & a five member ring.
•Precursor- arachidonic acid.
Two Classes:
1. Prostanoids: Prostaglandins, Prostacyclins. Thromboxane
2. Leukotrines .
• Present & synthesized in virtually every cell of the Body.
• local hormones
Prostaglandins –
Dr. Smita Pakhmode
Synthesis of Prostaglandins
Linoleic acid( from PL membrane)
Thromboxane
A2 synthase
Lipoxygenase
Arachidonic acid
Prostaglandin H2
synthase
Cycloxygenase
Prostaglandins (PG) Leukotrienes (LT)
Thromboxanes (TXA)
(PG)
Prostacyclin
PLA 2
Dr. Smita Pakhmode
Types of prostaglandins
PG-A , PG-B PG-D, PG-E, PG-F ,PG G
PG H ,PG I
Numbered according to presence of
double bonds & precursors.
PGD2,PGE2, PGI2 & Throboxane A2:
most commonly present PGs.
Naturally occurring PG re derived from
Arachidonic Acid.
Dr. Smita Pakhmode
Regulation of PG synthesis:
Significance of NSAID: Aspirin:
Irreversibly Inhibits Cyclooxygenase pathway.
Inhibit formation of TXA2 from platelets. & reduce platelets aggregation.
Hence used in Myocardial Infarction.
Idomethacin & Ibuprofen: Irreversible inhibitor.
Paracetamol: reversible inhibitor
Dr. Smita Pakhmode
Functions of Prostaglandins
PGE2 & PGD2 :Activation of the inflammatory response
Pain, and fever
Effect on CVS:
Prostacyclins (PGI2) Vasodilator & reduce Pl aggregation :Regulation of Blood
pressure.
Tx : Platelate aggregation, clotting & thrombosis.
fish food- PUFA --inhibit synthesis of tx & hence decrease heart attack & MI
Effect on Reproduction:
 PGE2 & PGF2: Contraction of smooth muscles of uterus: MTP/
Induction of labour
 Mobility of Spermatozoa: helps in Implantation of fertilized ovum
Aspirin/ PCM/Ibuprofen
Dr. Smita Pakhmode
Functions of Prostaglandins
 Gastric secretions……t/t of Ca stomach
 PGE2:Decreases functions of immune system

PGF is bronchoconstrictor while PGE2 is bronchodilators ( arosole)
GFR, Urine output
Metabolism- Lipolysis Glycogenesis, Ca mobilisation from bones
Functions of Leukotrienes:
Potent chemotactic agent
Acts as slow Responsible substances for development of
Anaphylaxis.
Smooth muscle contractor, Bronchoconstrictor, increases
capillary permeability.
Mediators of hypersesetivity reaction.
Dr. Smita Pakhmode
Bile salts:
Salts of bile acids with heavy metal
Bile Acids:
 Cholic Acid & Chenodeoxycholic acid
Glycine/ Taurine
 Glycocolic acids / Taurocolic acids
Na/K
 Na/K Glycocolate/ Na/K Taurocholate(Bile salts)
Dr. Smita Pakhmode
Dr. Smita Pakhmode,
Associate Professor , Biochemistry, NKP
SIMS & RC. Nagpur

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Lipid chemistry

  • 1. Dr. Smita Pakhmode LIPID CHEMISTRY Dr. Smita Pakhmode, Associate Professor , Biochemistry, NKP SIMS & RC. Nagpur
  • 2. Dr. Smita Pakhmode Com pete ncy No Competency Domain Core B14. 4 Describe and discuss main classes of lipids (Essential/non-essential fatty acids, cholesterol and hormonal steroids, triglycerides, major phospholipids and sphingolipids) relevant to human system and their major functions. K/KH Y
  • 3. Dr. Smita Pakhmode LIPID CHEMISTRY Lipid chemistry includes- Definition & Distribution of lipids in the body Describe & Discuss main classes of lipids ( Essential, non essential fatty acid, cholesterol, & Hormonal steroid, TAG, phospholipids & Spingophospholipids,) relevant to human system and their functions. Describe structure & functions of lipoproteins Describe therapeutic uses of PGS & inhibitors of eicosanoid system.
  • 4. Dr. Smita Pakhmode What are lipids: Heterogeneous group of substances: 1.Relatively insoluble in water 2. Freely soluble in non polar solvents (ether, benzene, chloroform, acetone) 3. Actually or potentially related to fatty acid. ( as esters of fatty acid with alcohol). 4. Utilized in metabolism by living cells.
  • 5. Dr. Smita Pakhmode  CH2OH CH2OH CHOH + HOOCR CH00CR Ester OF FA CH2 OH CH2 OH  Glycerol fatty acid Monoglyceride •Definition- Lipids are heterogeneous groups of compounds which are relatively insoluble in water & freely soluble in organic solvents. • Chemically lipids are esters of fatty acids with alcohol or substances capable of forming esters with fatty acids.
  • 6. Dr. Smita Pakhmode Occurrence of fats/ lipids in our body Fats are present- Beneath the skin – subcutaneous fat  Around the internal organs – mesenteric fats Nervous tissues and cell membrane - Cholesterol, Phospholipids, Glycolipids. Blood – Lipoproteins, Cholesterol. Storage form of fats ‘Adipose tissue’.
  • 7. Dr. Smita Pakhmode Biomedical importance of lipids ( functions of lipids) Storage form of energy. Insulating effect & padding give shape & contour to the body. Structural component of Biomembrane. necessary for cellular integrity. Source of Essential Fatty Acids (EFA) & fat soluble vitamins.
  • 8. Dr. Smita Pakhmode Biomedical importance: Metabolic regulators- steroid hormones & PG  second messenger- Phosphatidyl inositol blood clotting- The phosphatides of blood platelets As carriers – Lipoproteins • Constituent of nervous system • Components of inner mito memb ( in etc ). • Acts as a surfactant, detergent & emulsifying agent. Add taste &palatability to food
  • 9. Dr. Smita Pakhmode • INVOLVED WITH DISEASES LIKE ATHEROSCLEROSIS, FATTY LIVER, OBESITY Clinical Applications of Lipids Excessive fat deposit leads to Obesity. Abnormality Chol. & LP leads atherosclerosis & IHD Diabetes Mellitus leads to abnormal fat metabolism to Ketosis Lipdome & Lipidomics
  • 10. Dr. Smita Pakhmode Classification of lipids: four major types of lipids – 1)Simple lipids 2)Compound lipids 3)Derived lipids 4)Lipids complexed with other compounds.
  • 11. Dr. Smita Pakhmode 1) Simple lipids- b) waxes- esters of higher FA with alcohol other than glycerol (higher alcohol e.g. Cetyl alcohol) In human body common waxes are esters of cholesterol. 1. cholesterol ester 2. vitamin A ester 3. vitamin D ester Esters of fatty acids with alcohols Two types- a) Fats and oils: esters of FA with alcohol, glycerol Oils - liquid at room temp-
  • 12. Dr. Smita Pakhmode 2) Compound/ Complex lipids – Definition- Esters of FA with alcohol containing one or more additional group like phosphates, carbohydrates, nitrogen base, proteins etc.
  • 13. Phosphorylated lipids: Phosholipids FA + Alcohol+N2base+ Phosphoric acid 1. Glycerophospholipids: Lecithin, Cephalin, Plasmalogen, Cardiolipin etc. 2. Spingophosholipids: Sphingomylein Non Phosphorylated Lipids • Glycolipids: FA + Sphingosin+N2base+ Carbohydrate Cerebrosides :Ceramide Monohexoside Gangliosides: Ceramide oligosaccharides Globosides: Ceramide oligosaccharides + NANA • Sulfolipid: Sulfated Cerebroside, Sulfated Ganglioside, sulfated globoside
  • 15. Dr. Smita Pakhmode 3)Derived lipids Possess the properties of lipids. eg: Fatty acids, Glycerol, Cholesterol, Vit A, Vit D, Turpents, Leukotriens, and prostaglandins Derived Lipids simple lipids breakdown compound lipids
  • 16. Dr. Smita Pakhmode 4. Lipids complexed with other compounds: Lipoproteins: VLDL, , IDL, LDL, HDL & Free fatty acids. Proteolipids: protein covalently linked to lipid molecules, which can be fatty acids or sterols. Ex:, annexins, lipocortin, calpactin, endo- nexin, chromobindin, and anchorin.
  • 17. Dr. Smita Pakhmode Miscellaneous Lipids Squalenes Carotenoids Vitamin E Vitamin K Aliphatic hydrocarbons in bee’s wax, plant wax Chemically do not follow the definition of lipids but possess characteristics of lipids.
  • 18. Dr. Smita Pakhmode Neutral lipids Lipids which are uncharged eg: MAG, DAG, TAG. Cholesterol& chol. esters
  • 19. Dr. Smita Pakhmode Fatty acids (R-CH2-COOH) Carboxylic acid derivatives of long chain hydrocarbons. derived lipid  Simplest form, found in abundance.  majority are in esterified form - (CH2)n CH3 COOH n is almost always even n = 0 : CH3COOHn = 1 : propionic acid -anoic acid: Saturated fatty acid -enoic acid: Unsaturated acid
  • 20. Dr. Smita Pakhmode SATURATED FATTY ACIDS General formula: CH3 –(CH2) n-COOH  Acetic acid CH3COOH C2 Vinegar  Propionic acid CH3CH2COOH C3 Int. of metabolism  Butyric acid CH3(CH2)2COOH C4 butter  Caproic acid CH3(CH2)4COOH C6  Lauric acid CH3(CH2)10COOH C12  coconut oil  Myristic acid CH3(CH2)12COOH C14  Palmitic acid CH3(CH2)14COOH C16 Body fat  Stearic acid CH3(CH2)16COOH C18 plant EICOSA  Arachidic acid CH3(CH2)18 COOH C20 Peanut EICOSA Human body fat : 50% Oleic Aicid, 25%Palmitic Acid, 10% Linoleic acid & 5% Stearic acid
  • 21. Dr. Smita Pakhmode Unsaturated fatty acids Monoenoic acid (monounsaturated) Oleic acid H3C HOOC Double bond is always cis in natural fatty acids. This lowers the melting point due to “kink” in the chain Oleic acid 18:1; 9
  • 22. Dr. Smita Pakhmode Unsaturated fatty acids Polyenoic acid (polyunsaturated) Arachidonic acid COOH CH3 Arachidonic Acid 20:4; 5,8,11,14.
  • 23. Dr. Smita Pakhmode Unsaturated Fatty Acids Isomerism in unsaturated fatty acids: Cis Trans Less stable more stable L,U shaped Straight chain Naturally occurring Fast food & during FA metabolism Helps in compact Injurious to health Cell membrane Monounsaturated Polyunsaturated
  • 24. Dr. Smita Pakhmode Fatty Acids- Numbering System Two systems for numbering carbon atoms of fatty acids – 1)Delta system – numbering starts from carboxylic end. 2) Omega system – numbering starts from farthest carbon atom of FA.
  • 25. Dr. Smita Pakhmode CH3CH2-CH2CH2 CH2 CH2 CH2 CH2CH2CH2CH2CH2 CH2 CH2CH2-COOH • Palmitic acid 16:0 • omega endω α end CH3CH2CH2CH2-CH2CH2 =CH2 CH2CH2 =CH2CH2CH2CH2CH2 CH2 CH2CH2-COOH • Linoleic acid 18: 2; 9,12, • ω6 series CH3CH2CH2=CH2-CH2CH2 =CH2 CH2CH2 =CH2CH2CH2CH2CH2 CH2 CH2CH2-COOH Linolenic acid 18: 3; 9,12,15 ω3 series Biomedical Significance of ω3: Pleiotropic effects Positve role in infant brain development, Prevents Cancer, CVS,& mental illnesses like depression, ADHAD & dementia. Inflammation ,Pl aggregation, HT & Hyperlipidemia.
  • 26. Dr. Smita Pakhmode Classification 3) Nutritional classification Essential fatty acid (EFA) & Non essential fatty acids 1) According to structure: Even chain(Naturally occurring)/ Odd chain (Microbial cell wall & Milk) Saturated / unsaturated Cyclic/hydroxy/eicosanoids fatty acids (FA) 2)According to chain length: short chain FA: 2-6 carbon atoms medium chain FA: 8 –14 carbon atoms long chain FA: 16 – 24 carbon atoms Very long chain FA: > 24 carbon atoms
  • 27. Dr. Smita Pakhmode Composition of FA in dietary fats Mostly present in triacyl glycerol Animal sources- butter, lard, ghee, fish oil. - rich in saturated FA (40-50%) Plant sources - beans, seeds, leaves. - rich in unsaturated FA(80-90%) Simple Complex
  • 28. Dr. Smita Pakhmode How to choose oil:  High PUFA content. Cis FA prefered.  High ω3 /ω6 ratio. SFA:MFA:PUFA:- 1:1:1 Oil with high:  SFA: Palm, coconut & Ghee. MUFA: Groundnut, Mustard, Sesame oil. PUFA: Sunflower, Safflower, Soyabean,
  • 29. Dr. Smita Pakhmode Fatty acids Classification Saturated Acetic acid Lignoceric acid Sources Butter, Coconut oil, Animal fat, Arachis oil Unsaturated Oleic acid Linoleic acid Linolenic acid Arachidonic acid Sources All veg oils EFA Eicosanoids 20C cyclic PUFA Prostaglandins, Leukotrienes, Thromboxanes. Cyclic FA 1.Hydrocarpic acid 2.Chaulmoogric acid Sources Chaulmoogra oil Use- Treatment of leprosy Hydroxy FA 1.Ricinoleic Acid 2.Dihydroxy stearic acid Sources Caster oil 3.Cerebronic acid in brain 1 2 3 4 5
  • 30. Dr. Smita Pakhmode Essential Fatty Acids(PUFA) Essential Fatty acids are those which are not synthesized in the body& are essential in the diet. Lack Enzyme which introduces double bond beyond 9-10 - Linoleic acid(18:2 ;9,12) Sources: Corn oil, Peanut oil, Cottonseed oil,Soybean oil – Linolenic acid ( 18:3; 9,12,15) Sources: Walnuts, Wheat germ oil, Flaxeed oil, Fish liver oils/Fish eggs, Human Milk, Seafood/Fatty fish -Arachidonic acid- (20:4; 5, 8,11,14) Sources: plant oils
  • 31. Dr. Smita Pakhmode Conditionally Essential Fatty acid: Docohexanoic Acid( DHA, ω3 ;22:6) Linoleic Acid DHA Preterm Infant Imp. For developing brain Infant Nutrient formulas Fish oil EPA & DHA
  • 32. Dr. Smita Pakhmode Functions of EFA/PUFA 1. Formation of healthy cell membranes 2. Proper development and functioning of the Brain, Eye, Nervous system. 3.Necessary for lipoprotein synthesis 4. Transport & esterification of serum cholesterol. 5.Prevent fatty liver. 6.Production of hormone-like substances -- Eicosanoids (Thromboxanes, Leukotrienes, Prostaglandins ) 7. Regulation of blood pressure, blood viscosity, vasoconstriction, immune and inflammatory responses. 8. Role in reproduction. 9. Linolenic acid: required for optimal vision.
  • 33. Dr. Smita Pakhmode phrynoderma / toad skin. Acanthosis & Hyperkeratosis at extensor aspect. Found in 1.Infants on formula feeds, 2. IV nutrition
  • 34. Dr. Smita Pakhmode phrynoderma / toad skin.  Deficiency symptoms of EFA  Acanthosis & Hyperkeratosis at extensor aspect.  loss of hair.  Poor wound healing.  Cessation of growth.  Degenerative changes in arterial wall.  May lead fatty liver. Impaired LP Meta.
  • 35. Dr. Smita Pakhmode Triacylglycerols: Function: storage of energy in compact form and cushioning CH2OOCR | CHOH | CH2 OH CH2OOCR | CHOOCR | CH2 OH CH2OOCR | CHOOCR | CH2OOCR DAG TAG simple Mixed. Esters of trihydric alcohol Glycerol with Fatty acid. Neutral fat 1 2 3
  • 36. Dr. Smita Pakhmode Properties of Lipids: (TAG/ FA)  Oil --- Liquid, High Unsat FA & SCFA, Plant origin.  Fats --- Solid, High Sat. FA & LCFA, Animal origin.  MP increases with chain length and decreases with unsaturation  when shaken with water, oils tend to emulsify.  pure fats and oils colorless and odourless  (color and odour autooxidation ) - Physical :-
  • 37. Dr. Smita Pakhmode 37 Chemical :- 1] HYDROLYSIS (Lipolysis) – Sequential hydrolysis of TAG TAG DAG. MAG. 3FA + Glycerol Eg : by Lipases in digestion of fat in GIT Fat mobilization from adipose tissue 2] SAPONIFICATION Triglyceride + 3NaOH Glycerol +3 R-COONa “soap” Hydrolysis of TAG by alkali to produce glycerol & soap
  • 38. Dr. Smita Pakhmode 38 Hydrogenation glyceryl tripalmitoleate (tripalmitolean) glyceryl tripalmitate (tripalmitin) O (CH2)14CH3 C O (CH2)14CH3 C O (CH2)14CH3 C O O O CH2 CH2 CH CH(CH2)7CH3 (CH2)5CH O C CH(CH2)7CH3 (CH2)5CH O C CH(CH2)7CH3 (CH2)5CH O C O O O CH2 CH2 CH +3H2
  • 39. Dr. Smita Pakhmode Hydrogenation:  conversion of unsaturated fats to saturated ( Vanaspati from oil )  Makes oil/fat more stable to oxygen and temperature variation.  increase shelf life. Halogenation: Addition of two halogen atoms across double bonds to form Halide derivatives. Oleic acid + I2 Diidooleic acid No. of Halogen atoms directly proportional to ͠degree of saturation
  • 40. Dr. Smita Pakhmode RANCIDITY – Unpleasant taste & odour due to exposure to heat, light, moisture. unsuitable for consumption. Types: Hydrolytic: By bact. Enzymes. Oxidative Oxygen Fats/ Oil Ketones/ Aldehyde/ Dicarboxylic acid ANTIOXIDANTS in oils :- Vit E, Hydroquinones, gallic acid, α – napthol. Food preservatives Propyl Gallate, Butylated hydroxyanisol ( BHA ), BHT ( toluene)
  • 41. Dr. Smita Pakhmode Lipid peroxidation a non-enzymatic reaction catalyzed by oxygen may occur in tissues or in foods (spoilage). Unsaturated FA Peroxides + free radicals Oxidation of Protein/ DNA (Aging & Cancer) O2, H2O Autooxidatio
  • 42. Dr. Smita Pakhmode Antioxidants Substances that prevent auto oxidation in body or in stored fat ( Rancidity) are antioxidants. Antioxidants – Body – Vitamin E , A , C , Uric acid, Superoxide Dismutase, Glutathione Peroxidase. Preservative- Gallic acid, Phenols
  • 43. Dr. Smita Pakhmode Iodine No. –gms (No.) of iodine absorbed by 100 gm of fat or oil. Higher iodine no………… more is the degree of unsat. Helps in detection of adulteration of given oil. REICHERT MEISSL NO – Soluble volatile FA no. of ml of 0.1 N KOH req. to neutralize soluble volatile FA distilled from 5g of fat. (RM Of Butter: 25-30/ Oil : < 1) Useful in testing the purity of butter. Butter has high RM No. helps chemists identify butter substitutes. Tests to check purity of Fat
  • 44. Dr. Smita Pakhmode Saponification number  Defined as the milligrams of KOH needed to hydrolyse 1 Gm of fat or oil.  Measure of avg. molecular size & SC FA content.  If mol wt is more- less saponification no. Human fat- 195-200. Butter- 230-240 Cocconut oil– 250- 260 ACID NUMBER – mg of KOH required to completely neutralize FFA in 1g of fat or oil. Bacterial Or Chemical contamination forms FFA. Higher the no. more rancid is the oil.
  • 46. Dr. Smita Pakhmode Complex lipids Glycerophospholipids Composition- FA, N-base, Phosphate group, Glycerol. (alcohol) Sphingophospholipids Composition- FA,N- base Phosphate group, Sphingosine (alcohol) 1. Phospholipids – Two Types
  • 47. Dr. Smita Pakhmode Phosphatidic Acid In phosphatidate:  fatty acids are esterified to hydroxyls on C1(sat.) & C2(unsat.) the C3 hydroxyl is esterified to Pi. O P O O O H2C CH H2C O C R1 O O C O R2 phosphatidate R1 2
  • 48. Dr. Smita Pakhmode 48 Glycerophospholipids Glycerol PO4 N-Base Fatty acid Fatty acid (phosphoglycerides), are common constituents of cellular membranes
  • 49. polar non-polar "kink" due to double bond O P O O O H2C CH H2C O C R1 O O C O R2 X glycerophospholipid Each glycerophospholipid includes  a polar region: glycerol, carbonyl O of fatty acids, Pi, & the polar head group (X)  non-polar hydrocarbon tails of fatty acids (R1, R2).
  • 50. Dr. Smita Pakhmode 1)Lecithin (Phosphatidyl Choline) •abundant in cell memb, brain and nerve tissues. •found in egg yolk, wheat germ, and yeast d Functions: Bodys cholin reserve. Dissove chol . In bile Digestion & absorption of lipids . Esterification of free cholesterol. Forms lipoprotein complexes. Provide Arachidonic acid.
  • 51. Dr. Smita Pakhmode Dipalmitoyl lecithin  Surfactant Respiratory Distress syndrome: Common in premature infant. Def. of DPL Lecithin /spingomylein ratio: To asses the maturity in IU life
  • 52. Dr. Smita Pakhmode Lysolecithin Obtained by removal of one fatty acid from Lecithin.(c2) By enzymes Phospholipase A2 & LCAT H Acts as a detergent & haemolytic agents. Present in Viper snake venom
  • 53. Dr. Smita Pakhmode PHOSPHOLIPASE ACTION PL A1 PL A2 PL C PL D PLA1:- Acyl Glycerphosphoryl choline + FFA. PLA2 :- Lysolecithin PL C:- 1,2DAG + Phosphoryl choline. PL D:- Phospatidic acid + Choline.
  • 54. Dr. Smita Pakhmode 54 2)Cephalin (Phosphatidyl Ethanolamine) sur Surfactant Blood clotting Component of cell membrane. Important in Blood clotting.
  • 55. Dr. Smita Pakhmode 3)Phosphatidyl inositol Commonly utilized in cellular signaling (second messenger) Inositol
  • 56. Dr. Smita Pakhmode 4)Phosphatidyl Serine Inositol O- serine Present in nervous tissues & brain
  • 57. Dr. Smita Pakhmode Plasmalogen 5)Plasmalogen Possess an ether linkage at the C-1 position Ethanolamine 6)PAF potent mediator in inflammation allergic response
  • 58. Dr. Smita Pakhmode 6)Cardiolipin antigenic properties used in serologic test for syphilis (Wasserman test). Found in Mitochondrial membrane. ↓ levels: Heart failure, Hypothyroidism & Myopathies. Phosphatidic acid Phosphatidic acid Glycerol Joined by Glycerol bridge
  • 59. Dr. Smita Pakhmode Spingosine acts as a backbone Fatty acids are attached with amide linkage: Ceramide Phosphate group attached as ester bond wth alchohol and cholin Sphingophospholipids
  • 60. Sphingophospholipids •Found abundantly in brain,nervous tissue, RBC membrane. •Regulate protein kinase & phosphatase. •It is hydrolysed by Sphingomyelinase. • Inherited disorder - Niemann Pick’s disease Sphingomyelin AR, Hepatosplenomegaly & Mental Retardation 80% die within @ years Lecithin /spingomylein ratio: To asses the maturity in IU life
  • 61. Dr. Smita Pakhmode  Ceramide: The amino group of sphingosine can form an amide bond with a fatty acid carboxyl.  Devoid of Sugar.  Importance:  Second messenger in regulating cell cycle, cell differentiation and apoptosis.  Regulate skin water permiability. Anti phospholipid antibodies: Antibodies against membrane lipids, Cardiolipin Found in autoimmune disorders & Thromboitic episodes in pregnancy : Miscarriage, eclampsia, preterm labour
  • 62. Dr. Smita Pakhmode Functions of phospholipids  Lecithin –  Cephalins –  Phophatidyl inositol –  Phophatidyl serine –  Plasmalogen&  PAF.  Cardiolipins –  Lysolecithin –  Surfactant  Blood clotting  Second messenger  in brain, nervous tissue  Inflammation,allergies  Antigenic properties  Detergent & Haemolytic
  • 63. Dr. Smita Pakhmode - Acts as a lipotropic factor. Synthesis of Lipoprotein solublization & transport of cholesterol - ABSORBTION & TRANSPORT OF FAT - COMPONENTS OF BILE - PG SYNTHESIS FROM ARAC. ACID OTHER FUNCTIONS Regulates membrane permeability ETC ( maintaining conformation of components of etc.)
  • 64. Dr. Smita Pakhmode GLYCOLIPIDS ( NON PHOSPHORYLATED LIPID) Seen widely in nervous tissue. Ceramide= Sphingosine(Amino alcohol)+ Cerebronic acid (VLCFA) Glycolipids= CARBOHYDRATE + CERAMIDE Types of glycolipids: cerebrosides, Globosides gangliosides,
  • 65. Dr. Smita Pakhmode GLYCOLIPIDS  Cerebrosides  Ceramide + sugar molecule • Galactocerebroside – in neuronal membranes • Glucocerebrosides – non neuronal tissues. Gauchers disease: AR, Enzyme defect : Glucocerebrosidase. 3 Types: Adult, infantile, Juvenile. Hepatosplenomegaly, Anaemia, Erosion of bones. Bleeding tendency & Sec. Infections. In Infants: Growth & Mental retardation.
  • 66. Dr. Smita Pakhmode Gangliosides  Have a more complex oligosaccharide attached Ceramide + oligosaccharides with at least one mole. Of NANA.  Ceramide – Glu—Gal— NANA  Present in gray matter in high concentration.  Biological functions: cell-cell recognition; receptors for hormones.  common gangliosides:  GM1, GM2,, GD1a, GD1b, GT1a, GT1b,  Tay sachs Disease:  GM2 accumulates in neurons
  • 67. Dr. Smita Pakhmode GLYCOLIPIDS  Sulfatides or sulfogalactocerebrosides( also referred as sulpholipids) A sulfuric acid ester of galactocerebroside  Globosides: ceramide oligosaccharides Lactosylceramide • 2 sugars ( eg. lactose)
  • 68. Dr. Smita Pakhmode Lipid storage diseases(Sphigolipidoses) Disease Deficient enzyme Major storage compound 1.Niemann-Pick Sphingomyelinase Sphingomyelins 2.Goucher’s β-Glucosidase Cerebroside(glucose ) 3.Krabb’s β-Galactosidase Cerebroside(galacto se) 4.Tay-Sach’s Hexosaminidase A Gangliosides 5.Fabry’s α Galactosidase Ceramides
  • 70. Dr. Smita Pakhmode Amphipathic lipids  Molecules containing both hydrophilic & hydrophobic groups.  Examples:  1. Fatty Acids  2. Phospholipids  3Bile salts  4. Cholesterol
  • 71. Dr. Smita Pakhmode Cholesterol is largely hydrophobic. But it has one polar group, a hydroxyl, making it amphipathic. Cholesterol HO Cholesterol, an important constituent of cell membranes, has a rigid ring system and a short branched hydrocarbon tail. cholesterol PDB 1N83
  • 72. Dr. Smita Pakhmode Stable & permanent molecular arrangements:  Micelle: E.g., a spherical micelle  A bilayer: E.g. Membrane lipids  Liposomes:  Emulsions Bilayer Spherical Micelle Amphipathic lipids --complexes in which polar regions are in contact with water and hydrophobic regions away from water.
  • 73. Dr. Smita Pakhmode Liposome:  Sphere shaped vesicle consisting of one or more lipid bilayer enclosing water.  When Phospho lipids are sonicated with cholesterol, they are dispersed in the water to form vesicle or liposomes.  Intermidiate aqueous layer in lipid bilayer. Significance:  Carrier of drugs to target tissue  Used for gene transfer  Used in cancer chemotherapy.  Formation of vaccine  T/t of ophthalmic disorders. Second generation liposomes
  • 74. Dr. Smita Pakhmode Case studies:1  A 24 years women has put on weight after a child birth was advised by physician to reduce her calorie intake. Being impatient, she stopped consuming fats and oils. Though she lost excess weight . After a few months ,she developed a skin lesions on posterior and lateral aspects and her limbs and buttocks.  1.Identify the disease.  2What is its biochemical basis?  3Suggest the treatment.
  • 75. Dr. Smita Pakhmode Case studies:2 A preterm infant born to malnourished mother became dyspnoic ( difficulty in breathing). He was immidiately put on respiratory aids and necessary treatment was instituted. Diagnose the disease condition. What is biochemical basis of disease? What is line of treatment?
  • 77. Dr. Smita Pakhmode 77 Lipoproteins  Lipids complexed with other compounds  Def- Soluble molecular complexes of lipid with specific protein called apolipoprotein.  Function:1Transport of lipids in plasma .  2. Deliver lipids to tissue Lipoprotein classes: 1)chylomicrons: Dietary TAG from small intestine----------------------Tissue 2) very low density lipoproteins (VLDL) Endogeneous TAG from Liver--------------------tissue 3) low density lipoproteins (LDL) Chol from Liver ------------------ Tissue 4) high density lipoproteins (HDL) Chol from Tissue------------------ Liver 5) FFA-Albumin
  • 78. Dr. Smita Pakhmode Chylomicron LDL(Beta) VLDL(Pre Beta) FFA HDL( Alpha) Cathod (--) Anode (+) Point of origin Electrophoretic separation of Lipoproteins
  • 79. Dr. Smita Pakhmode Fraction Source Apoprotein Protein % Total Lipid % TG PL Chol Chylomicro n Intestine B48, CII, E 1-2 98-99 90 04 06 VLDL Liver & Intestine B100,CII, E 7-10 90-93 50 19 19 LDL Blood B 100 20 80 11 24 45 HDL Liver A, CII, E 33 67 05 30 18 Types of Lipoproteins •differ in density, composition, and function.
  • 80. Dr. Smita Pakhmode 80 Steroid Nucleus A steroid nucleus consists of CYCLOPENTANOPERHYDROPHENANTHRENE RING • 3 cyclohexane rings. • 1 cyclopentane ring. • no fatty acids. steroid nucleus
  • 81. Dr. Smita Pakhmode WIDELY DISTRIBUTED :- Plant – ergosterol & sitosterol Animal – Cholecalciferol, sex hormones, ACTH, Bile acid, cardiac glycosides. ( mainly in adrenal Cortex, brain, corpus luteum, testes, kid, liver )
  • 82. Dr. Smita Pakhmode 82 Cholesterol • most abundant steroid • has methyl CH3- groups, alkyl chain, and - OH attached to the steroid nucleus. C27H46OH H3 H3 H3 H3 H3
  • 83. Dr. Smita Pakhmode Free(30%) Occurence of cholesterol Total(70%)  Distribution:  Widely present in human tissue.  Present in brain & nervous tissue, liver , skin, endocrine glands, bile, blood.  Source:  Meat, milk, eggs, Denovosynthesis & from acetyl CoA.  Stored as:  cholesterol esters- LDL, HDL  Excretion:  Bile(60%), intestine & faeces.  Normal range: 150-250mg%.
  • 84. Dr. Smita Pakhmode 84 Cholesterol in the Body .Serum cholesterol • > 200mg/dl is considered to be high. • Blocks arteries when high levels, form plaque. An artery clogged by cholesterol plaque A normal, open artery.
  • 85. Dr. Smita Pakhmode Importance of Cholesterol Essential component of cell membrane Precursor of adrenocortical hormones- cortisol, aldosterone Precursor of sex hormones Estrogen, testosterone Precursor to bile acids Precursor of Vitamin D Insulator of nervous system Found only in animal products
  • 86. Dr. Smita Pakhmode Derived lipid • Unsaturated hydroxy acids, consisting of a 20 carbon skeleton & a five member ring. •Precursor- arachidonic acid. Two Classes: 1. Prostanoids: Prostaglandins, Prostacyclins. Thromboxane 2. Leukotrines . • Present & synthesized in virtually every cell of the Body. • local hormones Prostaglandins –
  • 87. Dr. Smita Pakhmode Synthesis of Prostaglandins Linoleic acid( from PL membrane) Thromboxane A2 synthase Lipoxygenase Arachidonic acid Prostaglandin H2 synthase Cycloxygenase Prostaglandins (PG) Leukotrienes (LT) Thromboxanes (TXA) (PG) Prostacyclin PLA 2
  • 88. Dr. Smita Pakhmode Types of prostaglandins PG-A , PG-B PG-D, PG-E, PG-F ,PG G PG H ,PG I Numbered according to presence of double bonds & precursors. PGD2,PGE2, PGI2 & Throboxane A2: most commonly present PGs. Naturally occurring PG re derived from Arachidonic Acid.
  • 89. Dr. Smita Pakhmode Regulation of PG synthesis: Significance of NSAID: Aspirin: Irreversibly Inhibits Cyclooxygenase pathway. Inhibit formation of TXA2 from platelets. & reduce platelets aggregation. Hence used in Myocardial Infarction. Idomethacin & Ibuprofen: Irreversible inhibitor. Paracetamol: reversible inhibitor
  • 90. Dr. Smita Pakhmode Functions of Prostaglandins PGE2 & PGD2 :Activation of the inflammatory response Pain, and fever Effect on CVS: Prostacyclins (PGI2) Vasodilator & reduce Pl aggregation :Regulation of Blood pressure. Tx : Platelate aggregation, clotting & thrombosis. fish food- PUFA --inhibit synthesis of tx & hence decrease heart attack & MI Effect on Reproduction:  PGE2 & PGF2: Contraction of smooth muscles of uterus: MTP/ Induction of labour  Mobility of Spermatozoa: helps in Implantation of fertilized ovum Aspirin/ PCM/Ibuprofen
  • 91. Dr. Smita Pakhmode Functions of Prostaglandins  Gastric secretions……t/t of Ca stomach  PGE2:Decreases functions of immune system  PGF is bronchoconstrictor while PGE2 is bronchodilators ( arosole) GFR, Urine output Metabolism- Lipolysis Glycogenesis, Ca mobilisation from bones Functions of Leukotrienes: Potent chemotactic agent Acts as slow Responsible substances for development of Anaphylaxis. Smooth muscle contractor, Bronchoconstrictor, increases capillary permeability. Mediators of hypersesetivity reaction.
  • 92. Dr. Smita Pakhmode Bile salts: Salts of bile acids with heavy metal Bile Acids:  Cholic Acid & Chenodeoxycholic acid Glycine/ Taurine  Glycocolic acids / Taurocolic acids Na/K  Na/K Glycocolate/ Na/K Taurocholate(Bile salts)
  • 93. Dr. Smita Pakhmode Dr. Smita Pakhmode, Associate Professor , Biochemistry, NKP SIMS & RC. Nagpur