Lipids are a class of heterogenous compounds which are relatively insoluble in water and soluble in nonpolar solvents.

Chemically: either esters of fatty acids or substances capable of forming such

esters

BIOMEDICAL IMPORTANCEBIOMEDICAL IMPORTANCE

Lipid (TGL)Droplets InAdipose tissue

1. Stored as a source of energy in the body.1. Stored as a source of energy in the body.

2. Structural components of biomembranes.2. Structural components of biomembranes.

3. Thermal Insulator : 3. Thermal Insulator : Provides insulation against changes in external Provides insulation against changes in external temperature.temperature.

4. Lipids act as electric insulators in neurons.4. Lipids act as electric insulators in neurons.

9. Associated with diseases such as atherosclerosis, 9. Associated with diseases such as atherosclerosis, diabetes mellitus and obesity.diabetes mellitus and obesity.

10. Gives shape and contour to the body.10. Gives shape and contour to the body.

6. Act as surfactants and prevents collapse of lungs during 6. Act as surfactants and prevents collapse of lungs during expiration.expiration.

8. Lipids used in emulsification and intestinal 8. Lipids used in emulsification and intestinal absorption of absorption of non polar nutrients like fatty acids and fat soluble non polar nutrients like fatty acids and fat soluble vitamins.vitamins.

5. Act as metabolic regulators (steroid hormones 5. Act as metabolic regulators (steroid hormones andand

prostaglandins).prostaglandins).

7. Lipids are used as detergents.7. Lipids are used as detergents.

1. Simple Lipids

2. Compound Lipids 3. Derived Lipids

LIPIDS

a. Fats :esters of fatty acids with glycerol.

eg: triglycerides.b. Waxes: esters of fatty acids with higher

molecular weight monohydric alcohols. eg: beeswax

1. Simple Lipids

Esters of fatty acids with various alcohols.Esters of fatty acids with various alcohols.

Glycerol

2. Compound LipidsEsters of fatty acids with various alcohols Esters of fatty acids with various alcohols

along along

with an additional group.with an additional group.

a. a. Phospholipids: Phospholipids:

b. b. Glycolipids:Glycolipids:

c. c. Other Complex Lipids:Other Complex Lipids:

Simple lipid + Additional group = Compound Lipids

COMPOUND LIPIDSEsters of fatty acids with various alcohols Esters of fatty acids with various alcohols along along

With an additional group.With an additional group.

Others Glycerphospholipids

-Phosphatidyl choline- Phosphatidyl

ethanolamine- Phosphatidyl serine- Phosphatidyl inositol- Cardiolipin- Plasmalogens

Sphingophospholipids

CerebrosidesGangliosidesGlobosides

LipoproteinsAminolipids

Phospholipids Glycolipids

3. Derived Lipids

Lipid molecules derived from simple/compound lipidsLipid molecules derived from simple/compound lipids

on their hydrolysison their hydrolysisFFatty acidsatty acids

EicosanoidesEicosanoides

SteroidsSteroids

SterolsSterols

CholesterolCholesterol

Bile acidsBile acids

Vitamins (A,D,E,K)Vitamins (A,D,E,K)

Ketone Bodies Ketone Bodies

GlycerolGlycerol

NAME ALCOHOL ACID EXAMPLE

Fats Glycerol Fatty acid Triglycerides

Waxes Aliphatic / Aromatic alcohol

Fatty acid Bees wax

SIMPLE LIPIDS

Phospho lipids

NAME ALCOHOL ACID Po4

ADDITIONAL GROUP

GLYCERO PHOSPHO LIPIDS

Phosphatidyl choline (lecithin)

Glycerol Fatty acid Po4 Choline

Phosphatidyl ethanolamine (cephalin)

Glycerol Fatty acid PO4 Ethanolamine

Phosphatidyl serine

Glycerol Fatty acid PO4 Serine

Phosphatidyl inositol

Glycerol Fatty acid PO4 Myoinositol

Cardiolipin Glycerol Fatty acid PO4 Phosphatidyl glycerol

Plasmologens Glycerol Fatty acid (ether link at C1)

PO4 Ethanolamine

SPHINGO PHOSPHO LIPIDS

Sphingomyelin Sphingosine

Fatty acid PO4 choline

NAME ALCOHOL ACID GLYCOSYL RESIDUE

ADDITIONAL GROUP

Cerebrosides

Sphingosine

Fatty acid (cerebronic acid)

Galactose/Glucose

Gangliosides

Sphingosine

Fatty acid Glucose Sialic acid

Globosides Sphingosine

Fatty acid Glucose +Galactose

Sulphatides Sphingosine

Fatty acid Galactose SO3

Glycolipids

Note:Ceramide: Sphingosine + Fatty acid

Slide 51

Based on ‘R’ group

3. Saturated / Unsaturated Fatty Acids

1. Small / Medium / Long Chain Fatty Acids

2. Odd / Even Chain Fatty Acids

CLASSIFICATION OF FATTY ACIDS

Essential / Non-Essential Fatty Acids

Nutritionally

1. Small / Medium / Long Chain Fatty Acids

Small chain Fatty acids : 2 – 4 carbons

Medium chain Fatty acids: 6 – 14 carbons

Long chain Fatty acids : more than 16 carbons

2. Odd / Even Chain Fatty Acids

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Saturated Fatty Acids

Unsaturated Fatty Acids

a) Mono unsaturated fatty acid (MUFA)eg., Oleic acid

b) Poly unsaturated fatty acid (PUFA)eg., Linoleic acid, Linoleinic acid, Arachidonic acid

c) Eicosanoids

a) Even chain fatty acideg., Palmitic acid

Stearic acid

b) Odd chain fatty acideg., Propionic acid

USES / FUNCTIONS OF PUFA

Major components of membrane lipids Contributes to the fluidity of membranes Used for Prostaglandin synthesis Decreases the incidence of Atherosclerosis,

Coronary Artery Diseases

Saturated fatty acids: rich in storage lipids (adipose tissue)

Unsaturated fatty acids: rich in membrane lipids (to increase fluidity)

Based on Nutrition

EssentialNon essential

Essential Fatty Acids

Fatty acids that can not be synthesized by body & has to be supplied by diet

Ex: Linoleic acidLinolenic acidArachidonic acid

Functions:Structural composition of Brain & Nervous systemPrecursor for Eicosanoid synthesisPrevents atherosclerosisPrevents skin lesions

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αβγδεω

Two types1. ω – type2. N - type

Indicating Number & Position of Double Bond

18:1,9

Δ9 18:1

ω9,C18:1ω3, ω6, ω9

Fatty Acids

Melting Point :

• Increases with increase in hydrocarbon chain length

• Saturated acids have high melting point than unsaturated acids

• Temperature at which fats are converted from solid state to liquid state.

Solubility:

Decreases with increasing chain lengthDecreases with increasing chain length Increases with temperature.Increases with temperature.

Unsaturated fatty acids exhibit cis-trans isomerism

GEOMETRIC ISOMERISM OF OLEIC AND ELAIDIC ACIDS

Natural Fatty acids – ‘cis’ form

1. Salt Formation2. Esterification3. Hydrogenation4. Halogenation5. Hydrolysis6. Oxidation

1. SALT FORMATION1. SALT FORMATION

R – COOH + NaCl R – COONa + HCl

Na+ or K+ salts of fatty acids : Soaps

Fatty acids react with alkalies to form Salts of fatty acids

2. ESTERIFICATION2. ESTERIFICATION

+ +

Most of the fatty acids of body are in esterified form

3. HYDROGENATION3. HYDROGENATION(hardening)(hardening)

H2

CH3 – CH2 – CH – CH – CH2 – COOH –

CH3 – CH2 – CH2 – CH2 – CH2 – COOH

Unsaturated FA converted to Saturated FA

Used to synthesize Vanaspathi & Margaraine

Trans Fatty acids are formed

4. HALOGENATION4. HALOGENATION

I2

CH3 – CH2 – CH – CH – CH2 – COOH –

CH3 – CH2 – CH – CH – CH2 – COOH

II

The amount of halogen taken by a fatty acid depends on

No of double bondsDegree of unsaturation

TAG undergoes stepwise hydrolysis of its ester bonds to form Glycerol & Free Fatty acids

Digestion of Fats in GITMobilisation of TGL from Adipose tissue

Lipases

GLYCERO PHOSPHOLIPIDS

Phosphatidic Acid

Choline

Ethanolamine

Serine

Inositol

PhosphatidylGlycerol

Phosphatidic acidPhosphatidyl

Plasmalogens

Phosphatidyl Choline (LECITHIN)

Choline

Phosphatidic acid + Choline

Lecithin acts as lung surfactant

Most abundant phospholipid of biomembranes

Phosphatidyl Choline (LECITHIN)

Dipalmitoyl Lecithin – Lung surfactant.

Synthesized by Alveolar type - II cells.

Reduces surface tension of alveolar fluid & prevents collapseduring expiration

Rich in alveolar fluid lining the alveoli

Deficiency in premature infants leads to collapse – Respiratory Distress syndrome

SITE OF ACTION OF PHOSPHOLIPASES

Phospholipase A1

Phospholipase A2

Phospholipase C

Phospholipase D

Sphingosine – alcohol moiety Commonly found in nerve tissues

SPHINGO PHOSPHOLIPIDS

SPHINGOPHOSPHOLIPIDS

Sphingomyelin

Sphingomyelin

SPHINGOPHOSPHOLIPIDS

1. Structural components of cell membrane.

2. Enable enzyme action.(mitochondrial enzyme system).

3. Required for blood coagulation (prothrombin to thrombin, activation of factor 8 by factor 9).

4. Transports lipids from intestine and liver.

5. Choline acts as a lipotropic agent since it prevents the formation of fatty liver.

6. Phospholipids of myelin sheath provides insulation around nerve fibers.

COMPOUND LIPIDS

Esters of fatty acids with various alcohols Esters of fatty acids with various alcohols along along

With an additional group.With an additional group.

Others

GlycerphospholipidsSphingophospholipids

CerebrosidesGangliosidesSulfatidesGlobosides

AminolipidsLipoproteins

Phospholipids Glycolipids

o Lipids containing carbohydrate moiety - Glycolipidso Alcoholic component – Sphingosine o Ceramide – Common group of all Glycolipids o Occur in brain, spinal cords and other tissues.o Predominant in outer leaflet of biomembranes

GANGLIOSIDES(Ceramide + Oligosaccharide + Sialic acid)

GM1 = Ganglioside with monosialic acid

GD2 = Ganglioside with two sialic acid residues

GT3 = Ganglioside with three sialic acid residues

Sialic acid = N-Acetyl Neuraminic acid (NANA)

1. Cerebrosides

2. Sulfatides

3. Globosides

4. Gangliosides

Types of Types of GlycolipidsGlycolipids

A B

C D1

2

3

4

5

10

9

8

7

6

11

12

13

14 15

16

1718

19

STEROIDS

Lipids containing Cyclo Pentano Perhydro Phenanthrene (CPPP) ring

STEROLS

Steroids containing alcoholic group - Sterols

Plant Sterols : Ergosterol, Stigmasterol, Sitosterol

Animal Sterols : Cholesterol

Chemistry: Has Steroid Nucleus OH group at 3rd position Double bond between 5th & 6th carbons 8-Carbon containing side chain at 17th position.

CHOLESTEROL

3 5

6

17

1. Undergoes rapid oxidation to form cholestenones.

2. Hydroxyl group forms esters with acids to form Cholesterol Esters (cholesterol acetate,palmitate and propionates)

3. Presence of double bond gives hydrogenation reactions (similar to unsaturated fatty acids).

4. Colour reactions: LIEBERMANN BURCHARD,

SALKOWSKY,

ZAKS.

CHOLESTEROL

Chemical Properties

CHOLESTEROL

Biomedical Importance

Structural role – Biomembranes, LipoproteinsStructural role – Biomembranes, LipoproteinsOccur in large amounts in brain and nerve tissues.Occur in large amounts in brain and nerve tissues.Act as insulator against nerve impulses which discharge Act as insulator against nerve impulses which discharge electric charges.electric charges.Biomolecules synthesized from cholesterolBiomolecules synthesized from cholesterol

Bile acids Bile acids Vitamin DVitamin DSteroid hormones : Steroid hormones :

Androgens, Estrogens, Progesterone, Androgens, Estrogens, Progesterone, Aldosterone etcAldosterone etc

Cholesterol is eliminated from the body as bile acids through bile.

Help in digestion & absorption of fats and fat soluble vitamins

Synthesised in liver, stored in gall bladder and act in intestine

BILE ACIDS

BILE ACIDS

Primary Bile Acids Secondary Bile Acids

Synthesised from Cholesterol in Hepatocytes

Ex:Cholic acidChenodeoxycholic acid

Synthesised from primary Bile acids in Intestine

Ex:Deoxycholic acidLithocholic acid

EICOSANOIDES

20 CARBON CONTAINING FATTY ACIDS GENERATED FROM ARACHIDONIC ACID

• Discovered in prostate gland secretions• Synthesized in all tissues• Acts as local hormones• Function in even low concentrations

EICOSANOIDES

Prostanoides Leukotrienes

ProstaglandinsThromboxanesProstacyclins

Lipoxins

COX LOX

OH

O

Protanoic acid – Precursor molecule

Cyclopentane ring substituted with hydroxyl / keto groupsBased on difference in these substituted groups, PGs classified as

PG-A, PG-B, PG-C, PG-D, PG-E, PG-F, PG-H

Based on number of double bonds, PGs have three series PG1 – One double bondPG2 – 2 double bondsPG3 – 3 double bonds

PG2 - most common series

Prostaglandin

Functions of prostaglandin

Smooth muscle contraction/relaxation Vaso constriction Broncho dilation (PGE2)

Uterine contraction (PGF2)

Capillary permeability Inflammation and pain Platelet aggregation

Unsaturated, substituted C-20 fatty acids with an oxaneUnsaturated, substituted C-20 fatty acids with an oxanering.ring.Occur in the cells of many tissues like blood platelets,Occur in the cells of many tissues like blood platelets,lung, brain etc.lung, brain etc.

Thromboxanes

PGI2 Vs TXA2

Prostacyclin (PGI2) Thromboxane (TXA2)

Produced mainly from vascular endothelium

Produced mainly from platelets

Smooth muscle relaxation Smooth muscle contraction

Inhibits platelet aggregation

Stimulates platelet aggregation

Leukotrienes, Lipoxins

Lipids having both hydrophobic and hydrophilic groups

Ex:

Phospholipids

Cholesterol

Glycolipids

Lipid Aggregates in Aqueous Compartment

Micelle Formation

Bilayer Formation

Liposome Formation

Prepared by sonication of amphipathic lipids

Liposomes (microscopic spherical vesicles) when mixed with water under special condition, the phospholipids arrange themselves to form a bilayer membrane enclosing water-filled central core

Impermeable to polar materials and helps maintain the composition of the enclosed aqueous fluid.

Liposomes

Uses of Liposomes

To deliverdrugsproteinsenzymesgenes

Drug release

Are spherical complexes made up of lipids andproteins .

STRUCTURESTRUCTURE

Amphipathic lipids & Proteins. Amphipathic lipids & Proteins.

Inner CoreInner Core

Nonpolar lipidsNonpolar lipids

Outer WallOuter Wall

TAG, Cholesterol esters Phospholipids, Cholesterol

Lipoproteins = lipids + proteins

Apoproteins

Al All Alll

B48 B100

Cl Cll

D

E

Functions of ApoproteinsFunctions of Apoproteins: :

1.1. Act as structural components of Act as structural components of lipoproteins.lipoproteins.

2. Recognize the cell membrane surface 2. Recognize the cell membrane surface receptors,.receptors,.

3. Activate enzymes involved in lipoprotein 3. Activate enzymes involved in lipoprotein

metabolism .metabolism .

TYPES OF LIPOPROTEINS

Based on density (lipid:protein ratio)

1. Chylomicrons1. Chylomicrons

2 . Very Low Density Lipoproteins 2 . Very Low Density Lipoproteins (VLDL) (VLDL)

3 .3 . Low Density Lipoproteins Low Density Lipoproteins (LDL)(LDL)

4 . High Density Lipoproteins 4 . High Density Lipoproteins (HDL)(HDL)

Ultracentrifugation Electrophoresis

Ultracentrifugation

HDL

LDL

IDL

VLDL

Chylomicrons

Electrophoresis

-ve

+ve

-ve

+ve

HDL

VLDL

IDL

LDL

Chylomicron

α -lipoprotein

β Lp

Pre β

Lipoprotein Apo lipoprotein Functions(trnspt Chol.,)

Chylomicron

Apo AI, AI, B48, CI, CII, CIII, E

Intestine to tissue

VLDL B100, CI, CII, CIII, E

Liver to tissue

LDL B100 Liver to tissue

IDL B100 Liver to tissue

HDL Apo AI, AII, AIV, CI, CII, CIII, E Tissue to liver

RANCIDITY OF FATS

Formation of unpleasant odour and taste in stored lipids is called as Rancidity.

• Denotes the deterioration of lipids & becomes unsuitable for consumption

• Occurs when exposed to air, moisture or bacteria

• TGL with unsaturated fatty acids more susceptible for rancidity

Types of Rancidity

1. Hydrolytic Rancidity: Partial hydrolysis of TGL by the bacterial enzymes

2. Oxidative Rancidity: Partial oxidation of fats leading to formation of peroxides & their corresponding aldehydes

Prevented by adding Anti-oxidants

LIPID PEROXIDATION

Lipid peroxidation - generates of free radicals ((ROOROO**,RO,RO**,OH,OH**))

Free radicals : Have unpaired electrons in their outer orbits They oxidize & damage any biomolecules

Peroxidation Peroxidation (free radicals)(free radicals)

: damages tissues in vivo, : damages tissues in vivo, causes of cancer, Inflammatory diseases, causes of cancer, Inflammatory diseases, atherosclerosis, and aging etc.atherosclerosis, and aging etc.

Lipids Lipid peroxidesFree Radicals

O2

Free Radicals+

1. Initiation

2. Propagation

3. Termination

Three Stages of Peroxidation

2. Chain Breaking Antioxidants: Interfere with chain propagation step.Ex : Superoxide dismutase(SOD), Vitamin E

Substances which control and prevent free radicals.Substances which control and prevent free radicals.

Types1. Preventive Antioxidants1. Preventive Antioxidants:: Decrease the rate of chain initiation step. Decrease the rate of chain initiation step.

Ex: Catalase, Metal ion chelators such as EDTAEx: Catalase, Metal ion chelators such as EDTA

Uses Protects biomembrane from the effect of free radicals Added in fats for storage purpose Protects the body from multiple diseases

Tests to check the purity of Simple Lipids

1. Iodine Number2. Saponification Number3. Reichert Miesel Number4. Acid Number5. Acetyl number

Defined as the number of grams of iodine taken up Defined as the number of grams of iodine taken up

by 100gms of fat.by 100gms of fat.

Index of degree of unsaturationIodine Number degree of unsaturationع

Uses:To detect the degree of unsaturationTo detect adulteration

Fats / Oils Iodine No

Coconut oil 7-10

Butter 25-28

Groundnut oil 85-100

Sunflower oil 125-135

IODINE NUMBER

SAPONIFICATION NUMBER

Defined as the number of milligrams (mgs) of Defined as the number of milligrams (mgs) of potassiumpotassium

Hydroxide (KOH) required to saponify one gram of fat.Hydroxide (KOH) required to saponify one gram of fat.

Index of molecular weight / chain length fatty acids

Saponification Number عmolecular weight (or) chain length

1

Uses:To detect molecular weight / chain length fatty acidsTo detect adulteration

Castor oil has acetyl value of 146 to 150 indicating thepresence of sufficient hydroxylated acids.

Butter has an acetyl value of 1.9 to 8.6 ,indicating thepresence of very small amounts of hydroxylated acids.

ACETYL NUMBER

Defined as the Milligrams of KOH required to Defined as the Milligrams of KOH required to combine with the acetic acid liberated by the combine with the acetic acid liberated by the saponification of saponification of

1 gm of acetylated fat.1 gm of acetylated fat.Indicator of number of hydroxyl groups

Butter fat has a Reichert-Meissl number of 26-33whereas the number for lard is 0.6.

REICHERT-MEISSL NUMBER

Defined as the millimeters of 0.1N alkali required to Defined as the millimeters of 0.1N alkali required to neutralize the volatile acids obtained from 5 gm of neutralize the volatile acids obtained from 5 gm of fat .fat .

It is of value in determining rancidity due tofree fatty acids.

ACID NUMBER

Defined as the Milligrams of KOH required to Defined as the Milligrams of KOH required to neutralize the free fatty acids present in 1gm of fat.neutralize the free fatty acids present in 1gm of fat.