Chmistry of Lipids-2012

8/2/2019 Chmistry of Lipids-2012

1/28

CHEMISTRY OF LIPIDSDefinition of lipids:

Lipids are heterogeneous group of compounds that are highly insoluble in water, but are

soluble in non-polar solvents like Benzene, Chloroform, ether, alcohol e.t.c.

Biological Roles of Lipids

Lipids perform several important functions

1. Lipids are the concentrated fuel reserves of the body (Triglycerides)

2. Lipids involves in the construction of all biological membranes.

3. Lipids are the sources of the fat soluble vitamins (A, D, E, K)

4. Some lipids acts as cellular metabolic regulators

(steroid hormones and prostaglandins)

5. Lipids act as the thermal insulators and maintain the body temperature

6. Lipids act as electrical insulators and help the neuronal transmissions.

7. Lipids make diet palatable (tasty)

CLASSIFICATION OF LIPIDS


2/28

2

1. FATTY ACIDS

Fatty Acids are carboxylic acids with aliphatic hydrocarbon side chain.

These are the simplest Lipids.

Fatty acids mainly occur in the esterified form as major constituents of various lipids,

they are also present in free form

Based on presence of single or double covalent bonds fatty acids are divided in to

Saturated Fatty acids: Do not contain double bonds

Unsatur(ated Fatty acids: Contain double bonds

Mono unsaturated fatty acids: Contains one single double bond

Poly unsaturated fatty acids: Contains two or more double bonds

Numbering of carbon atoms in Fatty acids

There are different types of numbering systems

10 9 8 7 6 5 4 3 2 1 Delta numbering system

CH3CHCH =CH2CH2CH2CH2CH2CH2COOH

Greek letters

1 2 3 4 5 6 7 8 9 10 Omega numbering system

Counting carbons with Greek alphabets

The first CH2 adjacent to the carboxyl group is named as , and so on

The last carbon with CH3 group is called as omega () carbon

Delta ( ) system:

Carbons are numbered from COOH end to CH3

Carboxyl carbon (COOH) is counted as 1, and carbon with CH3 as the last

Above fatty acid is 10: 1 or 10:1;7

(Total 10 carbons: 1 double bond between 7&8 carbons)

Omega () system:

Carbons are numbered from CH3 to COOH

CH3 is counted as 1 and COOH as the last


3/28

3

Above fatty acid is 10:17 (10 carbons: 1 double bond between 3&4carbons)

Length of Fatty acids:

Short chain fatty acids: with less than 6 carbons

Medium chain Fatty acids: with 8-14 carbons

Long chain Fatty acids: with 16-24 carbons

List of Important saturated fatty acids

Common name Numbering

Acetic acid 2:0

Propionic acid 3:0

Butyric Acid 4:0

Valeric Acid 5:0

Caproic acid 6:0

Capric acid 10:0

Palmitic acid 16:0

Stearic acid 18:0

Arachadic acid 20:0

List of Important Unsaturated Fatty acids

Common name ngmberig- girebmgn- Palmitoleic acid cis16: 1; 9 16:1 7

Oleic acid cis18:1;9 18:19

Linoleic acid All cis18: 2;9,12 18:2 6,9

Linolenic acid All cis18:3;9,12,15 18:3 3,6, 9

Arachidonic Acid All cis20:4; 5,8,11,14 20: 4 6,9,12,15


4/28

4

Even and Odd Carbon Fatty acids:

Most of the fatty acids that occur in natural lipids are even carbons.

Most common even carbon fatty acids: Palmitic acid (16C) and Stearic acid (18C)

Most common odd carbon fatty acids: Propionic acid (3C) and valeric acid (5C)

Isomerism in unsaturated fatty acids

Unsaturated fatty acids shows geometric isomerism depending on the orientation of the

groups around the double bond

Cis configuration:

Similar groups are present on the same side of the double bond.

Trans configuration:

Similar groups are present on the opposite side of the double bond.

Essential fatty acids:

The fatty acids that cannot be synthesized by the body and therefore should be supplied

in the diet are known as essential fatty acids.

Essential fatty acids are chemically poly unsaturated fatty acids. They are

Linoleic aicd ( 18:2;9,12)

Linolenic acid( 18:3; 9,12,15)

Arachidonic acid (20:4;5,8,11,14) becomes essential when its precursor linoleic acid is

not supplied in diet.


5/28

5

Essential fatty acids are present in vegetable oils, and fish oils

Functions of essential fatty acids:

Normal growth of the body

Formation of cell membrane

Transport of cholesterol

Formation of lipoproteins

Formation of eco sanoids

Protects against atherosclerosis

Non essential fatty acids: These can be synthesized by the body

These are saturated and mono unsaturated fatty acids

Synthesized from acetyl-CoA which is derived from glucose oxidation

2. SIMPLE LIPIDS

Esters of Fatty acids with alcohol

There are two types of simple lipids

i. Triacylglycerols (Fats & Oils), ii. Waxes

i. Triacylglycerols (Fats & Oils)

Esters of 3 fatty acids with a glycerol

COOH group of fatty acids condenses with OH of glycerol and forms ester link


6/28

6

Triacylglycerol = 3 fatty acids are esterified to glycerol

Also known as Triglycerides and neutral fats

Insoluble in water and soluble in non-polar solvents

They are fuel reserves of animal, stored in the adipose tissue

The fat stored in normal men 20% women 25% of the body weight

Triglycerides are not found in biological membranes.

Triglyceride up on hydrolysis gives diacylglycerols and monoacylglycerols

Based on the type of fatty acids present triglycerides are divided in to

Simple triglycerides: Contains the same type of fatty acids at all the three carbons

Mixed triglycerides: Contains 2 or 3 different types of fatty acids

Mixed triglycerides are more common in nature.

Oil: triglyceride with one or more unsaturated fatty acids exists as liquid at room

temperature termed as oil

Plant triglycerides are having higher content of unsaturated fatty acids compared to thatof animals.

Hence animal fat will be solid and plant fat is liquid at room temperature

Properties of Triglycerides:

a) Hydrolysis:

Triglyceride +3 H2O Lipase 3 Fatty acids + Glycerol

This reaction helps the digestion and absorption of the fat from the intestine

Also helps the mobilization of fat from the adipose tissue.

b) Saponification:

Triglyceride + 3 NaOH 3 Fatty acidsNa (Soap) + Glycerol

The alkali can be sodium hydroxide (NaOH), or Potassium Hydroxide (KOH).

In the intestine soaps are formed with bile salts known as emulsification


7/28

7

Emulsification process helps the easy absorption of fats from the intestine

c) Rancidity:

Oxidation of fat due to air, moisture, light, Bacteria is known as rancidity

Oxidation takes place at double bonds of the free fatty acids

Fats will be spoiled due to rancidity, the taste and smell will be unpleasant

Steps and types in rancidity

Hydrolytic rancidity:

Triglycerides are hydrolysed by bacterial lipase to produce glycerol + free fatty acids

Free fatty acids undergo further oxidative and ketonic rancidity.

Hydrolysis increases in presence of moisture and warm temperature

Oxidative rancidity: oxidation at double bonds forms peroxides

Ketonic rancidity: peroxidesat double bond decomposes to form aldehydes & ketones

Enhancers of rancidity:

Oxidizing agents like nascent oxygen (O), Pb2+

, Cu2+

, Fe2+

(Heme), Lipoxygenase

Detection of rancidity: Copper acetate reacts with free fatty acids

Prevention of rancidity:

Prevention of fat for the exposure to light and moisture

Addition of antioxidants like Vit-C, E and molecules withSH group (cystine)


8/28

8

ii) Waxes: Esters of long chain fatty acids with long chain monohydric alcohols.

Eg: Bee wax, sebaceous secretion, cuticles of leaves

Waxes are not hydrolysed by lipase, hence animals cannot digest the wax

Waxes are solids at room temperature, highly hydrophobic

3. COMPLEX OR COMPOUND LIPIDS

Alcohol + Fatty acid + Some other molecule

There are three major types of complex (compound) lipids are present

i. Phospho Lipids ii. Glyco Lipids iii. Lipoproteins

They are further divided in to

i. Phospho Lipids

A) Glycero Phospho Lipids

a) Phosphatidic acid

b) Lecithin

c) Cephalin

d) Phosphotidyl Inositole) Phosphotidyl serine

f) Plasmalogen

g) Cardio Lipin

B) Phospho Sphingo lipids

a) Sphingomylin

ii. Glyco Lipids ( Glycosphingo lipids)

a) Cerebrosides

b) Gangliosides

iii. Lipoproteins


9/28

9

i. Phospho Lipids: These lipids contain alcohol + Fatty acids + phosphoric acid.

There are two classes of phospho lipids

A) Glycerophospholipids (Phosphoglycerides): contain glycerol as the alcohol

B) Sphingophospholipids: Contains shingosine as the alcohol.

A) Glycerophospholipids (Phosphoglycerides):

a) Phosphatidic acid:

Glycerol esterified with a

Saturated fatty acid at carbon 1,

Unsaturated fatty acid at its carbon 2

Phosphoric acid at carbon 3

b) Lecithins ( Phosphotidyl Choline)

Choline attached to phosphate of phosphatidic acid

Carbon:1 = Saturated fatty acid

Carbon: 2 = Unsaturated fatty acid

Carbon 3: phosphoric acid + choline

Functions of lecithin

Construction of cell membrane Formation of lecithin cholesterol esters

Lecithin + Cholesterol

Lecithin cholesterol acyltransferase (LCAT)

Cholesterol ester (Cholesterol-Fatty acid) + Lysolecithin

Cholesterol esters are taken to liver, mixed in bile and excreted

Absence of lecithin increases cholesterol in the blood, leads to atherosclerosis


10/28

1

Lecithin in bile prevents formation of gall stones (cholesterolstones) Storage of choline: lecithin acts as store for choline

Choline involves in neurotransmissions (forms acetyl choline)

Choline prevents accumulation of fat in liver (lipotropicfactor)

Choline gives methyl group for methylation reactions

Dipalmitoyl lecithin: Is a surfactant (decreases surfacetension)found in lungs and prevents the adherence of inner surfaces of lungs due to the

surface tension

dipalmitoyl lecithin is less produced in premature infants causing respiratory failure

this condition is known as respiratory distress syndrome.

c) Cephalin ( Phosphotidyl Ethanolamine):

Ethanolamine attached to phosphatidic acid is termed as cephalin or phosphatidyl

ethanolamine

Involves in blood coagulation mechanism

d) Lipositol (Phosphotidyl Inositol) : Inositol attached to the phosphatidic acid.

This is an important component of cell membranes.

Acts as a second messenger in Ca2+

dependent hormonal actions


11/28

e) phosphotidyl Serine The aminoacid serine is attached to phosphatidic acid

found in brain, blood and other tissues

f) Plasmalogens

Fatty aldehyde attached at C1 of glycerophospholipids by ether link known as

plasmalogens.

Lecithin with fatty aldehyde at C1 = phosphatidal choline

Cephalin with fatty aldehyde at C1 = phosphatidal ethanolamine

Present in brain and muscle

g) Cardiolipin: Two molecules of phosphotidic acids attached to a glycerol through

their phosphoric acid groups is called cardiolipin.

Cardiolipin is an important component of inner mitochndrial membrane.


12/28

2

B) Sphingo Phospho Lipids:

Sphingo lipids contain sphingosine as alcohol, they do not contain glycerol

Sphingo lipids are found in brain and nervous tissue.

a) Ceramide: Fatty acid + Sphingosine

Fatty acid attached to Sphingosine through

amide link in ceramide

b) Sphingomyelin: Fatty acid+ Sphingosine+ Phosphric acid+ Choline

Choline is attached to the phosphate of ceramide through ester link

Present in nervous tissue and brain

Niemann picks disease

Accumulation of sphingomyelin in liver,spleen and brain

Caused by the deficiency of an enzyme sphingomyelinase

Clinical findings are enlargement of liver & spleen, and mental retardation

Functions of Phospholipids:

Construction of cell membranes and regulates the cell permeability.

Helps the absorption of fat from the intestine,

Involves in the synthesis of lipoproteins

Acts as surfactants, eg: Dipalmitoyl lecithin in lungs.


13/28

3

Prevents the accumulation of fat in liver

Involves in cholesterol metabolism

Cephalin participates in blood clotting.

Phosphatidyl inositol participates in signal transduction across the cell membrane.

ii. Glycolipids:

Present in cell membranes and nervous tissue,

Contains sphingosine + fatty caid + carbohydrate,

There are two important classes of glycolipids.

a) Cerebrosides b) Gagliosides

a) Cerebrosides:

These are the simplest glycolipids contains

Sphingosine + Fatty acid (ceramide) + sugar (galctose or glucose).

Present in brain, nervous tissue

Acts as insulators for neurotransmissions

Gauchers disease:

Cerebrosides accumulate in liver, spleen and bone marrow.

Because of the deficiency ofenzyme glucocerebrosidase

Spleen and liver will be enlarged


14/28

4

b) Gangliosides: These are complex glycosphingolipids

Ceramide attached to N-acetyl neuramnic acid (sialic acid) and other mono saccharides.

The important gangliosides present in the brain are GM1, GM2, GD, GT

Also present in membrane receptors

Where: G= Ganglioside; M= Mono sialic acid residue

D= Di sialic acid residues T=Tri sialic acid residues

Tay sachs disease: accumulation of GM2 gangliosides in brain, spleen

Because of deficiency of an enzyme hexosaminidase A

Leads to mental retardation, blindness and muscular weakness

iii. Lipoproteins: = Lipid + apolipoprotein

Lipids combined with proteins are termed as lipoproteins

The proteins present in lipoproteins are known as apolipoproteins

Apolipoproteins are mostly globulins in nature

Lipids present in lipoproteins are triglycerides, phospholipids, cholesterol, cholesterol

esters and free fatty acids

Lipoprotein helps the transport of lipids in the blood, and in and out of the cells

Lipoproteins involves in the construction of cell membrane

If lipid concentration increases the density of lipoprotein decreases

If the lipid concentration decreases the density of lipoprotein increases


15/28

5

Classification of lipoproteins based on centrifugation

Lipoproteins can be separated by centrifugation based on their relative densities

They are mainly divided in to 4 classes

Type Lipids present Important

Apolipoproteins present

Chylomicrons Triglycerides apo-A-I,A-II,C-I,C-II

VLDL Triglycerides, cholesterol apo-B-100,C-I,C-II,E

IDL Less TG & cholesterol apo-B-100,C-I, C-II,E

LDL Cholesterol

Cholesterol esters

Phospholipids

apo-B-100,C-I, C-II,E

HDL Cholesterol

Cholesterol esters

Phospholipids

apo- A-I, A-II,E,D

Free fatty acids-Albumin Free fatty acids Albumin

Functions of apo-lipoproteins

Transport of lipids (gives hydrophilic covering for lipids)

Binds membrane receptors


16/28

6

Regulates enzyme activities (Activates /inhibits)

Electrophoretic separation of lipoproteins

Proteins present in the lipoproteins shows charge (ve & +ve)

During electrophoresis lipoproteins will separate based on their charge

4. DERIVED LIPIDS

Hydrolysis or chemical modification of simple or complex lipids gives derived lipids

Some of important derived lipids are

Fatty acids

Ecosanoids

Glycerol

Steroids & Sterols (Cholesterol, Vitamin-D, Bile acids & Salts, Sex hormones)

Separation

basedo

n

density

Centrifugation Electrophoresis

Separation

basedo

n

charge

CM CM

VLDL LDL ( lipoproteins)

LDL VLDL (pre lipoproteins)

HDL HDL ( lipoproteins)

FFA-albumin Free fatty acids-Albumin +


17/28

7

i) ECOSANOIDS

Cyclic compounds that are derived from arachidonic acid (20 C poly unsaturated)

Note: Ecosa = 20

Ecosanoids acts like local hormones

They are derived in to two types

A) Prostanoids

Prostaglandins (PG)

Prostacyclines (PGI)

Thromboxanes (Tx)

B) Leukotriens (LT)

A) Prostanoids

a) Prostaglandins

There are four main groups of prostaglandins are present A, B, E, and F

Recently some more groups are identified like, C,D,H,G,I,X

Causes vasodilatation, and contraction of uterus & intestine,

b) Prostacyclines

Causes vasodilatation

Prevents platelet aggregation

c) Thromboxanes

Causes vasoconstriction

Enhances platelet aggregation

B) Leukotriens

Are present in leukocytes

Causes chemo taxis of leukocytes towards the site of inflammation


18/28


19/28

9

a)Cholesterol:

Structure:

Steroid nucleus attached with an aliphatic side chain at carbon 17

Aliphatic side chain contains 8 carbons; hence cholesterol contains total 27 carbons

Hydroxyl group (-OH) is present at carbon 3

Double bond between carbons 5-6

Cholesterol contains five methyl (CH3) groups ( C18, C19, C21, C26, C27).

Properties and functions of cholesterol

Cholesterol is a yellowish crystalline solid in nature Cholesterol is the most abundant animal sterolCholesterol is found only in animals.

Cholesterol is present cell membranes (increases fluidity of cell membrane)

Cholesterol is a poor conductor of heat and electricity hence functions as insulator for

nervous tissue.

Cholesterol involves in the synthesis of Bile acids, steroid hormones and Vitamin-D.


20/28

21

b) Vitamin D: Is synthesized from cholesterol in animals

Ergosterol (Fungi) Cholesterol (Animals)

U.V light U.V light (In skin)

Vitamin D2 (ergocalciferol) Vitamin D3 (cholecalciferol)

By enzyme 25,Hydroxylase

in Intestine

25,hydroxy cholecalciferol (Calcidiol)

1- Hydroxylase

in Kidneys

1,25 dihydroxy cholecalciferol (Clacitriol) is the active form of vitamin-D


21/28


22/28

22

Bile salts: Sodium salts of conjugated bile acids

Eg: sodium glycocholate, Sodium tauro cholate

Functions of bile salts

Helps in digestion and absorption of lipids from the intestine (emulsification)

Stimulates liver to secrete more bile (choleretic effect)

Prevents formation of cholesterol stones


23/28

23

d) Steroid Hormones:

There are two major classes of steroid hormones

All the steroid hormones are derived from cholesterol

i) Sex Hormones:

a) Estrogens (Female sex hormones)

Estrone Estradiol Estriolb) Progestins (Female sex hormones)

Progesteronc) Androgens (Male sex hormones)

Testosterone Dihydrotestosterone

ii) Adrinocortical hormones

a) Gluco corticoids

Corticosterone Cortisol Dehydrocorticosterone Cortisoneb) Mineralo corticoids

Aldosterone 11-deoxy corticosterone

i) Sex hormones:

a) Estrogen: Is a female sex hormone

There are three types of estrogens Estrone (E1), Estradiol (E2), Estriol (E3)

Estradiol (E2) is the most active estrogen

Structure:

Ring A is unsaturated

-OH group at C3

Hydroxyl group at C17

Methyl group (C18) at C13

Site of production:

Females: Ovary, Placenta, Adrenal cortex (minor amounts)

Males: Testes, Adrenal cortex (minor amounts)

Functions: Development of female secondary sexual characters

Anabolic effect on bones and cartilage


24/28


25/28

25

Stimulates spermatogenesis, Shows anabolic effect on proteins

ii. Adrenal cortical hormones:

Adrenal cortical hormones are mainly divided in to two types

Are produced from adrenal cortex

a) Glucocorticoids: Corticosterone, Dehydrocorticosterone, Cortisol , Cortisone

They regulates the carbohydrates, Fat and protein metabolisms

Shows catabolic effect on fat and protein metabolisms

Shows anabolic effect on carbohydrate metabolism

b) Mineralcorticoids: Aldosterone, 11-deoxy corticosterone

Regulates the mineral metabolism

Acts on kidneys stimulates secretion of K+, H

+and reabsorption of Na

+

All adrenal cortical hormones are derived by slight modifications of corticosterone

Corticosterone structure

Keotne group at C3

Double bond between C4& C5

-OH at C11

Methyl groups at C10,C13

Ketol group at C17


26/28

26

5. FREE RADICALS AND ANTIOXIDANTS

Free Radical:

a molecule or atom that contains one or more unpaired electrons, and is capable of

independent existence.

Different types of free radicals produced in the body

O (singlet oxygen / nascent oxygen)

O2-

(Super Oxide radical)

OH-

( Hydroxyl Radical)

HOO-

( Hydro Peroxy Radical)

ROO-

(Lipid Peroxy Radical)

Free radicals are formed during the normal metabolism in presence of oxygen or metal

ions ( Cu++

, Fe++

) they are highly reactive.

Free radicals can generate new free radicals by chain reaction

Free radicals damages the cell membranes and biomolecules


27/28


28/28

Antioxidants:

The molecules that can stop or slow down the oxidation of lipids and other

biomolecules are termed as anti oxidants.

i) Natural anti oxidants: These are of two types:

a) Preventive antioxidants:

Reduces the rate of chain initiation (first step of lipid peroxidation)

Eg: Catalase, Glutathione peroxidase, selenium

EDTA( Ethylene Diamine Tetra Acetate)

DTPA ( Diethylene Triamine Penta Acetate)

b) Chain Breaking Anti Oxidants:

They stops the chain elongation, (second step of the lipid peroxidation)

eg: Super oxide desmutase ( SOD)

Vitamin-E, Vitamin-C

ii. Artificial antioxidants : These are chemically synthesized

Added in lipid based foods to prevent the oxidation of lipids ( Rancidity) in the food.

Eg: Propyl Gallate,

Butylated Hydroxy anisole (BHA)

Butylated Hydroxy Toluene (BHT)

Chmistry of Lipids-2012

Documents

Transcript of Chmistry of Lipids-2012