LIPIDS
LIPIDS
LIPIDS
Professor Dr. Muhammad Shafique, MBBS, M.Phil, Ph.D.
Definitions
Classifications
Common Blood Lipids
Chemistry, Sources & Structures
Types & Structures of Fatty Acids
Overall Biomedical importance
Importance of Essential Fatty Acids
Neutral Fats & Cholesterol
Phospholipids & Sphingolipids
Inherited disorders (sphingolipidoses)
Biochemistry of Prostaglandins 2
Definition
These are organic chemical
compounds which are esters of
fatty acids with alcohols. These
are insoluble in water & soluble in
non polar solvents like ether,
chloroform, benzene, acetone.
They are utilized by the living
organisms.
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Classification
Based on Hydrolysis (Important)
I Simple Lipids Esters of Fatty acids with alcohols. Theses are:
V Miscellaneous
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Fats vs Waxes
1. These are esters of fatty acids with glycerol. Esters of fatty acids with cetyl alcohol or other high molecular
weight alcohols.
2. These contain trihydric alcohol which is glycerol.
Usually contain monohydroxy alcohol.
3. Abundently stored in body as animal fats.
Not stored in body.
4. Also present in nuts seeds, oils. Not present in oils but mainly in honey comb, wool & whale.
Examples are beeswax, lanolin and spermaceti.
5. Examples are monoacylglycerol,
Diacylglycerol & triacylglycerols. Comparatively higher.
6. Specific gravity lower even than water. Not usually digested & absorbed.
Saponifiable
Non - Saponifiable
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SAPONIFIABLE LIPIDS VS NON-SAPONIFIABLE LIPIDS
7. Forms esters and fatty acids. 8. If they are present they are in negligible
amounts.
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(IV) Based on Sources
Plant Vegetable oils, corn oil, soyabean oil, sunflower oil, cotton seed oil,
olive oil, palm oil, coconut oil.
I. Based on Density:
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CEREBROSIDES VS GANGLIOSIDES
CEREBROSIDES GANGLIOSIDES
(GLYCOLIPIDS)
(GLYCOLIPIDS)
1. Mainly in gray matter of brain
1. Mainly in white matter of brain
2. not common.
2. 24 C carbonic acid is common.
3. It is present in these.
3. Sialic acid not common.
4. These are prominent in these.
4. N-acetyl nuraminic acid and N acetyl
hexosamine are not present.
5. They have receptors and
5. Usually they are determinants of blood neurotransmitters.
groups A & B.
6. They are GM1 and GM3 etc.
6. They are cerebron neurons.
7. Enzyme Hexosaminidase metabolizes
7. Enzyme Glucocerebrosidase metabolizes them.
them.
8. They contain several sugar units.
8. They contain one sugar unit (hexose).
9. Excessive accumulation leads to Tay-
9. Excessive accumulation leads to Sachs disease.
Gauchers disease. 12
Common Blood Lipids
Cholesterol
Triacylglycerol
Phospholipids
Fatty Acids
Lipoproteins ( HDL, VDL, VLDL, Chylomicron)
Dietary Sources
Milk and Milk Prducts
Eggs, especially egg yolk
Beaf, Meat ( Brain, liver, Kidney)
Vegetable Ghee and Oils
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Main Functions
Rich source of energy. 9.1 Kcal/gm
Good energy reservoirs in body
Carriers of fat- soluble vitamins
Carriers of essential fatty acids
Integral part of protoplasm and cell membranes
Provide contour to body and stability to organs i.e. kidneys
Decrease gastric motility and have high satiety value
Exert insulating effect on nervous tissues
Act as precursors of various compounds
Cholesterol: Bile acids
Vitamin D3
Steroid hormones
I. Based on Saturation
II.Based on Nutrition:
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III. Based on Length of Chain
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III. Based on Esterification
2. Unesterified: 5%. These are free but transported by albumin. Their level in
plasma is 10-15 mg/dl.
IV Based on Isomerism
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VIII. Based on Melting Points
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Saturated Fatty Acids
Common Name C Atoms Formula Source & Significance
Butyric Acid 4 C3H7COOH Fats, Butter, end product of
CHO fermentation of rumen
Caproic Acid 6 C5H11COOH organisms
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Lignoceric Acid 24 C23H47COOH Peanuts, cerebrosides
Unsaturated Fatty Acids
Name Formula Source & Significance
C15H29COOH =16:1,9 Monoenoic. In all fats provide
Palmito-oleic 7 energy.
10. No Halogenation and Hydrogen action occur in 10. Halogenation and Hydrogen action occur in them.
them.
11. Oxidized in the body. 11. More rapidly oxidized in the body.
13. Don`t form prostaglandins and leucotriens. 13. 20 carbons Arachidonic acid forms them.
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Functions of Essential Fatty Acids
Formation of prostaglandins and leukotrienes
Associated with structural elements of tissues.
Part of structural elements of mitochondrial membrane.
Maintain the integrity of reproductive system.
Maintain the normal skin and epithelium.
Lower serum cholesterol level.
Increased CT is noted in excessive intake of EFA
Increased fibrinolytic activity follows excessive intake of EFA.
Linolenic acid is necessary in diet for optimal vision.
Deficiency produces low growth skin lesions & fatty liver.
Deficiency also leads to defects in pregnancy & lactation ,
kidney damage & retinitis pigmentosa. 23
ESSENTIAL FATTY ACIDS VS NON-ESSENTIAL FATTY ACIDS
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HYDROLYSIS: By superheated steam, acids ,alkalies & enzymes-
lipases into glycerol and FAs. Lipases are :- Lingual,gastric,
intestinal & pancreatic lipases ; aipolytic lipase & serum lipase
SAPONIFICATION: fats boiled with strong base e.g.NaOH,KOH,
yield glycerol and salt of fatty acid (soap).SAPONIFICATION.NO:
mg of KOH required to saponify 1 gm of fat.
HYDROGENATION: unsaturated F.A.of glyceroids is hydrogenated
to partially or fully saturated F.A.esters (oil changes to ghee,in
presence of Ni). IODINE NO: (gms of iodine absorbed by 100 gms
of fat),This is measure of degree of unsaturation of fat.
OXIDATION: FAs of fats are oxidized in body producing energy.
RANCIDITY; fats get unpleasant odour and taste on aging
(unsaturated F.A. form peroxide linkage by reacting with
atmospheric O2. Second reason of rancidity is of fat hydrolysis.
Rancidity can be prevented by antioxidants i.e. Vit.E.
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Neutral Fats ( Triacylglycerol)
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IODINE NUMBER VS SAPONIFICATION NUMBER
IODINE NUMBER SAPONIFICATION NUMBER
Types
Glycerophospholipids
Lecithin
Cephalin
Phosphotidic acid
Plasmalogens
Cardiolipins
Sphingophospholipids
Sphingomyelins
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30
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Functions of Phospholipids
Structural component in tissue & membranes
Component in bile secretion
Acts as detergent in bile
Solubilize cholesterol in bile
Acts as signal transmission across cell membranes
Certain enzymes require PL for their actions – Oxidative Phosphorylation
Play role in blood coagulation process
Lecithin lower surface tension and emulsification in GIT.
Have a role in transport of lipids from liver
Have role in electron transport and oxidative phosphorylation
Choline in lecithin acts as lipotropic agent
Have a role in ion transport & secretion of hormones and enzymes
Membrane PL are source of arachidonic acid
PL of myelin sheaths provide insulation on nerve fibers
Are co-factors for activity of enzymes – LPL & TAG Lipase
Phosphatidyl inositides metabolite has role in Ca dependent hormone action
Dipalmityl Lecithin (DPL) acts as surfactant in lungs.
Lecithin / Sphingomyelin (L/S) ratio is used for evaluating of fetal lung
maturity. Low ratio indicates RDS
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Plasmalogens
These are glycerophospholipids.
Present in brain, nervous tissue, sk.muscles & mitochondria
Also present in heart, liver & platelets
Contain glycerol ,F.A., phosphate & ethanolamine/choline
On hydrolysis liberate fatty aldehyde instead of F.A.
These appear to be resistant to phospholipases
Contain vinyl ether at carbon no:1 of glycerol
Give +ive reaction with schiff ‘s reagent (fuchsin-sulphurous
acid) after treatment of phospholipid with mercuric chloride
due to presence of aldehyde group
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Cardiolipins
1. It is a phospholipid
2. Formed from phosphatidyl glycerol
3. Found in mitochondria (inner membrane)
4. Also found in bacterial wall
5. Chemically, is diphosphatidyl glycerol
6. It is only phosphoglyceride that possesses
antigenic properties.
1. On hydrolysis yield:-
- 4 mols of fatty acids
- 3 mols of glycerol
- 2 mols of phosphoric acid
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GLYCOLIPIDS
Cerebrosides
One sugar molecule
• Galactocerebroside – in neuronal membranes
• Glucocerebrosides – elsewhere in the body
Sulfatides or sulfogalactocerebrosides
A sulfuric acid ester of galactocerebroside
Globosides: ceramide oligosaccharides
Lactosylceramide
• 2 sugars ( eg. lactose)
Gangliosides
Have a more complex oligosaccharide attached
Biological functions: cell-cell recognition; receptors for
hormones 35
Gangliosides
complex glycosphingolipids that consist of
a ceramide backbone with 3 or more
sugars esterified,one of these being a
sialic acid such as N-acetylneuraminic
acid
common gangliosides: GM1, GM2, GM3, GD1a,
GD1b, GT1a, GT1b, Gq1b
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N-Acetyl-D-galactosamine D-galactose D-glucose
H O H
H H H H
O
H OH H NH H OH H OH
H H
C O HO C C CH2
D-Galactose
CH3 H NH
C
O H O C O
H3C C NH O COO- C R
CHOH H
CHOH
CH2OH H
H
OH H
A ganglioside (GM1)
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Lipid storage diseases
also known as sphingolipidoses
genetically acquired
due to the deficiency or absence of a catabolic
enzyme
examples:
Tay Sachs disease
Gaucher’s disease
Niemann-Pick disease
Fabry’s disease
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Cholesterol: General View
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Dietary Sources
Exogenous
Butter, cream and milk &milk products
Eggs, especially egg yolk
Beef, meat :– brain, liver and kidney
Endogenous
Synthesized in tissues in liver etc: I gm/day
Forms of Cholesterol
Free Cholesterol 30%
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Risks of high cholesterol
Atherosclerosis
Hypertension
Heart Diseases
Brain Strokes
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HOW to lower Cholesterol
Unsaturated fats
Regular Exercise
Reduction of weight
Heredity
TG LOWERING
Lifestyl interventions
Glycemic control
Fibric acid derivative (gemfibrozil, fenofibrate)
Niacin
High-dose statin (if high LDL-C)
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TRIACYLGLYCEROL VS CHOLESTEROL
TRIACYLGLYCEROL(FATS) CHOLESTEROL(STEROLS)
1. It is a simple lipid fat in nature 1. It is of miscellaneous group sterol in nature
2. Esters of fatty acids with glycerol
2. Esters may or may not be present.
3. Contains variable C atoms.
4. Fatty acids can be esterified. 3. Contains 27 C atoms.
5. Most common lipid.
6. Also found in oils. 4. One fatty acid can esterify.
7. Stores are present in the body.
8. Specific gravity low. 5. Comparatively less common.
9. Cause saponification (soaps formation)
10. Have iodine number. 6. Not found in oils.
11. Not contain steroid nucleus.
12. Mainly carried by Chylomicron and 7. Not stored in the body.
VLDL.
8. Specific gravity higher than fats.
13. Can be hydrolyzed by lipase.
9. Not important in this respect.
14. Provides energy.
10. Have no iodine number.
15. Glycerol part can convert into glucose or
glycogen. 11. Contains nucleus (CPPP)
16. Blood level ranges between 12. Mainly carried by LDL & HDL.
70-150mg/dl.
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Important Features:
Present almost in all tissues and body fluids.
Production increases or decreases in response to drugs.
They are produced in minute amounts.
Broad spectrum and diverse biological effects.
They are not stored in the body.
Their action is through cAMP activity.
All PGs are 20 C FAs containing cyclopentane ring.
All PGs have OH group at 15 C position.
All PGs have trans double bond at 13 C position.
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Prostaglandins Functions:
Antihypertensive : lowers BP.
Inhibits platelets aggregation.
Inhibits gastric secretion.
Stimulate int. peristalsis ( Purgative action ).
Bronchodilatation: used in bronchial asthma.
Increase uterine contraction: used in labour.
Increase GFR: causes diuresis.
Lower lipolysis but increase steroidogenesis.
Metabolically has insulin- like effect.
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Prostacyclins (PGI2)
Derived from arachidonic acid
Contain cyclopentane ring
Action through cyclic AMP
Inhibit platelet Aggregation
Produce vasodilatation
Prevent thrombus formation
Relax coronary arteries
Lower blood pressure
Inhibit gastric secretion
Thromboxanes (Tx)
Derived from arachidonic acid
Contain an oxane ring
Formed mainly in platelets
Decrease cyclic AMP
Enhance platelets aggregation
Produce vasoconstriction
Favour thrombus formation
Produce contraction of smooth muscles
Raise blood pressure
Induce release of serotonin, Ca & ADP
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Leukotrienes -LTs
Derived from arachidonic acid
Formed in leucocytes & mast cells
Mediate inflammation & anaphylaxis
Cause capillary dilatation & permeability
Cause bronchospasm
Stimulate mucus secretion in airways
Stimulate chemotaxis & chemokinesis of neutrophils & eosinophils,
which are found in large no. at the site of inflammation.
Lipoxins (Lx)
These are conjugated tetraenes
Derived from arachidonic acid
Formed in leucocytes by lipoxygenase pathway
Many types discovered i.e. Lx-A 4 to Lx –E4
have role in vasoactive & immunoregulatory function e.g.
counter-regulation of the immune response
NSAIDs-Aspirin
Used in angina & myocardial infarction
An Effective anti-platelet aggregator
Prolonged use causes bronchial asthma
Causes blood dilution
Causes gastritis & bleeding disorders
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Examination Room-3
The external examiners in deptt. of Biochemistry, Agha khan
university Karachi, asked the following questions regarding lipids:
1. Define lipids and name various fat solvents.
2. Difference b/w lecithin and lysolecithin.
3. What is ceramide and its significance?
4. What is DPL and its significance?
5. Name various glycolipids with examples.
6. Name types & components of ganglioside mol.
7. What is Gaucher’s disease, and enzyme involved?
8. Name essential fatty acids & their significance.
9. Name omega-3,omega-6,omega-9 fatty acids with significance.
10. Difference b/w sterols & steroids.
11. What is rancidity of fats & how it is prevented?
12. What is iodine number & saponification number?
13. What is the difference b/w oil and fat?
14. Structure & functions of cholesterol.
15. What are lipotropic factors? Name them.
16. Enumerate Lipoproteins types with their functions.
17. What are Chylomicrons? Their composition & hydrolysis.
18. Composition of HDL and Biomedical importance.
19. Difference b/w prostacyclins & thromboxanes.
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20. What do you know about prostaglandins and their biomedical role?
Thank You 55
End OF
The Topic 56