LECTURE NOTES ON LIPIDS

Lipids constitute a heterogeneous group of organic compounds found in plants and animals
that are insoluble in water but soluble in one or more organic solvents like ether, alcohol
or acetone .
Lipids are amphyphilic meaning that parts of them hate water while other parts love it. The
part that hate water is said to be hydrophobic while the part that love water is said to be
hydrophilic.

BLOOR’S CRITERIA FOR LIPIDS

All lipids must have one or more of the following characteristics;
(1) Insolubility in water
(2) Solubility in one or more organic solvents
(3) Actual or potential relationship to a fatty acid
(4) Capacity of utilization by a living system
FUNCTIONS OF LIPIDS
(1) Lipids function as storage form of energy (easy storability)
(2) Good and efficient source of energy (provides more energy than carbohydrates wt
by wt)
(3) Structural component of bio-membranes (Phospholipids and Cholesterols)
(4) Serve as metabolic regulators eg Hormones and Prostaglandins
(5) They serve as surfactants, detergents and emulsifying agents eg (amphipathic lipids)
(6) Act as insulators eg in neurons myelin sheat
(7) Gives contour and shape to the body
(8) Protection and cushioning effect (Pad of Fat )
(9) Help in absorption of Fat soluble Vitamins (A, D, E, K)
(10) Gives taste and palatability to food
(11) Lipids Function as chaperons (Helps in folding of protein into its native
conformation)
(12) Function as heating Furnace ( For thoracic organs)

CLASSIFICATION OF LIPIDS
Lipids are classified into Four Main classes

(1) Simple lipids

(2) Compound lipids
(3) Derived lipids and
(4) Lipids complexed to other compounds
 (1) Simple Lipids
These are esters of fatty acids with glycerol or other higher aliphatic fatty acids

(a) Neutral Fat or Triacylglycerols (TG or TAG); These are triesters of Glycerol with fatty
acids
(b) Waxes ; These are esters of fatty acids with long chain aliphatic alcohols eg Cetyl
Alcohol
(c) Vit D and Vit A Esters
(d) Cholesterol Esters

(II) Compound Lipids;

These contain in addition to fatty acids and alcohol . other substituents eg Phosphoric acid
moiety, carbohydrate moiety , a nitrogenous base or a sulphate group. Depending on the
groups they contain, they are classified as follows;
(A) Phosphate Containing lipids or Glycerophospholipids
(1) Nitrogen containing Glycerophospholipids ; These contain fatty acids, Glycerol.
Phosphoric acid and a anitrogenous base eg
+
(i) Phosphatidylcholine (Lecithin) -CH2CH2N (CH3)3
(ii) PhosphatidylEthanolamine ( Cephalin) -CH2CH2NH2
(iii) Phosphatidylserine CH2OHCHCOOH(NH2)

(2) Non-Nitrogen Glycerophospholipids

(i) Phosphatidyl Inositol (Lipositol)
(ii) Phosphatidyl glycerol
(iii) Diphosphatidylglycerol (Cardiolipin)
(3) Plasmalogens having Long chain Alcohols
(i) Choline Plasmalogen
(ii) Ethanolamine Plasmalogen
(4) PhosphoSphingosides with Sphingosine
Sphingomyelins

(B) Non-Phosphorylated Lipids

(1) Glycosphingolipids (Carbohydrates)
i Cerebrosides (Ceramide Monohexosides)
ii Globosides (Ceramide Oligosaccharides)
iii Gangliosides (Ceramide plus Oligosaccharides plus N-acetylneuraminic acid)
(2) Sulfolipids or Sulfatides
I Sulfated Cerebrosides
 Ii Sulfated globosides
Iii Sulfated gangliosides
(III) Derived Lipids

These are hydrolytic products of the first two groups that still possess lipid characteristics
I Fatty Acids
Ii Glycerols
Iii Cholesterols

Iv Terpenes
v Dolichols etc
vi Monoglycerides and Diglycerides
vii VitA and certain carotenoids

(IV) Lipids Complexed to other Compounds

I Proteolipids
Ii Lipoproteins
(V) Miscallaneous
( i ) Aliphatic Hydrocarbons including isooctadecane found in liver fat and long chain
alcohols from wax hydrolysis (bee wax and plant waxes)
( ii ) Carotenoids
(iii) Squalene (A hydrocarbon in Sharks and mammalian liver and in sebum)
(iv) Vit E and Vit K

DERIVED LIPIDS
(A) Fatty Acids
Fatty Acids are Derived Lipids. It is the most common component of Lipids in the body. They
are generally found in ester linkages in different classes of Lipids. They are monocarboxylic
acids with the general Formular R-CO—OH. The ---COOH group represents the functional
group. They are obtained from the hydrolysis of fats. The physical properties of a fatty acid
would vary depending on the length of R group.
Classification of Fatty Acids

Fatty acids can be classified based on a number of qualities or criteria

(1) Based on the total number of Carbon atoms
(i) Even Chains; These have even number of carbon atoms eg 2,4,8,10 etc. Most
naturally occurring fatty acids are even number fatty acids.
 (ii) Odd chain fatty acids; Here the fatty acids have odd numbers like 3,5,7,9 etc.
Odd number fatty acids are present in microbial cell walls and inmilk.
(2) Depending on the Lengty of Hydrocarbon Chain
(i) Short chain Fatty Acids (2-6 Carbon atoms)
(ii) Medium chain Fatty Acids (8-14 carbon atoms)
(iii) Long Chain Fatty Acids (16 and above up to 24)
(iv) Very long Chain Fatty Acids *24 and above)
(3) Based on nature of hydrocarbon Chain
(i) Straight Chain Fatty Acids; Could be Saturated eg Palmitic Acid or
Unsaturated
(ii) Unsaturated Fatty Acids could Further be classifies into
(a) Monounsaturated fatty acids eg Oleic acid (18:1;9). (Genral Formula
CnH2n-1COOH)
(b) Polyunsaturated Fatty Acids (PUFA).These are the essential Fatty Acids
(c) Linoleic Acid Series (18:2;9,12) General FormulaCnH2n-3COOH Abound in
peanut oil, corn oil ,cotton seed oil soyabean oil and Egg yolk.
(d) Linolenic Acid series(18:3;9,12,15) General Formula CnH2n-5COOH They
have three double bonds Abound in Linseed oil, Rapeseed oil, Soyabean
oil, Fish viscera and cord liver oil.
(e) Arachidonic Acid Series (20:4;5,8,11,14) Have Four double bonds. General
Formula CnH2n-7COOH .Found along with linoleic and Linolenic Acids esp.
in peanuts and Liver fat
(iii) Branched Chain Fatty Acids; Could be even or odd numbered. Both are found
in animal and plant lipids
(a) Sebaceous gland sebum contains branched chain fatty acids
(b) Branched chain Fatty Acids are found insome foods eg butter contains
Phytanic acid
(c) Mycobacterium tuberculosis contain trehalose-6-6-dimycolate
responsible for its cord-like growth known as cord factor in trace
amounts. This cord factor contained in its cell wall is responsible for its
virulence.
(d) Substituted Fatty Acids
Both saturated and unsaturated hydroxyl and methyl fatty acids
abound in nature ;eg cerebronic acid of brain gangliosides and
Ricinoleic Acid in castor oil
(e) Cyclic Fatty Acids Fatty acids bearing cyclic groups abound in nature
(f) ^Eicosanoids; These are derived from Eicosapolyenoic fatty acids
Eicosapolyenoic Fatty Acids
(1) Prostanoids ; These include Prostaglandins(PGs), Prostacyclins
(PGI) andThromboxanes (Tx) These have cyclic Structure
(2) Leucotrienes (LTs) and Lipoxins (LXs) These are strait chains
NOMENCLSATURE OF FATTY ACIDS
(a) More frequently Fatty Acids are named after the corresponding hydrocarbon by
addition of the surfix anoic or enoic for saturated and unsaturated fatty acids
respectively, to the name of the hydrocarbon eg Octane (10C) becomes Octanoic
acid (For Saturated) . Octadecenoic Acid (Oleic acid)
(b) Carbon atoms are numbered with the –COOH being given number 1 and the next
carbon no 2 etcs Alternatively, the carbon next to the -COOH is called the α carbon,
the next ie No 3 carbon is named the B and so on with the -CH3 carbon being named
the w-carbon
(c) Various conventions are used to indicate the position of double bonds like 9 or ^9
indicate a double bond between C9-C10.
(d) More generally, each Fatty acid is represented by a formula to indicate (i0 Number
of Cs, (ii) Number of double bonds and (iii) their relative positions.eg
CH3(CH2)7CH=CH(CH2)7COOH Oleic Acid is represented by (18:1,9)
18 indicate number of carbon atoms
1 indicate number of double bonds
9 indicate the position of double bonds
ISOMERISM
Two types of isomers abound .They are (a)Geometric Isomers due to orientation in space eg
Oleic acid and Elaidic acid and (b) Positional isomers. By altering the position of the = bond,
a different isomer is produced.
PROPERTIES OF FATTY ACIDS
(a) Unsaturated fatty acids can be hydrogenated (becomes saturated) and this leads to
solidification
(b) They can undergo halogenation reactions eg Oleic acid forms Diiodo oleic acid
The more iodine taken up ,the more the iodine number and the more the degree of un-
saturation
(c) Short and medium chain FAs are liquids, and long chain fatty acids are solid at 25o C.
Water solubility decreases while melting point and boiling point increases as chain
length increases
(d) Unsaturated fatty acids have lower M.Ps than the corresponding saturated fatty
acids. The more the degree of un-saturation , the lower the boiling and melting
points eg Stearic acid ( C18,no = bond), MP is 69oC, Oleic acid (C18, 1 double bond
)has MP of 13oC , Linoleic acid(C18, 2 double bonds ) ,Mp is -5oC and linolenic acid
(C18,3double bonds) has MP of -10oC.
(e) All fatty acids form salt with alkali to form Salt (Soap) and water.
(f) Hydrogenation Unsaturated Fatty Acids can tahe up hydrogen and become
saturated. Hydrogenation of oils can lead to solidification eg Vanaspathi. The amount
of H taken up per unit of Fat is an index of the degree of unsaturation.
 Linolenic acid —> Linoleic acid —> Oleic Acid —> Stearic Acid
+2H +2H +2H
(g) Halogenation Under mild treatment conditions, un-saturated Fatty Acids can take
up two atoms of a halogen per double bond
Oleic Acid + I2 —>> Di-iodo oleic Acid
The number of Halogen atoms taken up is an index of the degree of unsaturation
(See Iodine Number)
(h) Melting Point The higher the chain length, the higher the melting and points and
the lower the solubility in water.
Short and medium FAs are liquid at 25oC
Long chain FAs are solid at 25oC
Unsaturated FAs have even much lower melting point, the higher the unsaturation,
the lower the melting and boiling point
Eg Stearic acid (C18 FA, no =bond) melts at 69oC;
Oleic Acid (C18 FA, One =bond) melts at 13oC
Linoleic Acid (C18 FA, 2 =bonds) melts at -5oC
Linolenic Acid (C18 FA, 3==bonds) MP is -10oC.
(i) Salt Formation Both saturated and unsaturated FAs form salts with Alkali
CH3-COOH + NaOH ——> CH3—COONa + H2O
Sodium and Potassium salts of LCFAs are called Soaps
Calcium and Magnesium salts are insoluble
Calcium soaps are used as grease
Alkyl Sulfate (R-CH2-O-SO2-ONa) and Alkyl Sulfonate (R-CH2-SO2-ONa) are not
precipitated by hard water and are used as Detergents.s
(j) Ester Formation All fatty acids form esters with Alcohols eg glycerol, Cholesterol
etc. Also mono- and diacyl – and Triacyl- glycerol (neutral fats) form through such a
reaction.
Glycerol + FFA ------> Monoacylglycerol
Monoacylglycerol (MAG) + FFA ------> Diacylglycerol
Diacylglycerol + FFA ------------> Triacylglycerol
Oxidation of Fatty Acids All fatty Acids undergo B-oxidation to yield energy in the
body. Unsaturated FAS on account of their =bonds can undergo orthooxidation to yield
various short chain aldehydes, acids and ketones(Rancidity) .This gives the FA bad odour,
colour and taste-a process known as rancidity.

GLYCEROL

i) Is commonly called glycerine

ii) Is the simplest trihydric alcohol
iii) It is colourless oily liquid with sweetish smell
iv) Miscible with water and alcohol in all proportions
v) Almost insoluble in ether
Source
i) As a byproduct of soapmanufacture
 ii) Also from fermentation of glucose by altering reaction condition to limit CO2 formation
and alcohol
iii) Endogenously from lipolysis of depot fat
iv) Exogenous—From intestinal absorption (approx 22%)

TESTS FOR GLYCEROL

Acrolein Test

Presence of glycerol is detected by Acrolein test. Glycerol when dehydrated by heat and KHSO 4;
produces acryl aldehyde which has pungent or acrid odour

CH2OHCHOHCH2OH ----------→ CH2=CH-CHO

Glycerol -2H2O Acrolein (acryl aldehyde)

Dehydrated with

Heat and KHSO4

Uses

i) As solvent in industries ; because of its solubility (solvent nature) and hygroscopic nature
ii) Present in most cosmetics and pharmaceutical industries.
iii) Nitroglycerin is used in medicine as drugs
iv) Glycerol therapy is used to reduce cerebral oedema in cerebrovascular disease (CVD)
v) Also has nutritive value, Convertible to glucose and glycogen (gluconeogenesis)

STEROIDS AND STEROLS

i) Are found in association with fats

ii) Constitutes unsaponifiable part left after saponification of fat
iii) All contain cyclopentano perhydro-phenantrene nucleus.
Ie Phenanthrene (ring A,B,C) attached to Cyclopentane ring ( ring D)
iv) Methyl side chains at positions 10 and13 represent C 18 and C19 respectively
v) A side chain at position is usual.
vi) In the Presence of –OH and no –CO of –COOH group, it becomes a sterol eg Cholesterol;
Chief sterol in human

CHOLESTEROL
i) Most important sterol in man
ii) Molecular formula is C27H45OH
iii) Structural formula below
 iv) Has cyclopentano perphenanthrene nucleus typical of all steroids
v) It has an –OH group at C3
vi) Has a =bond between C5 and C6
vii) Has two –CH3 groups at C18 and C19
viii) It has a C18 side chain attached to C17

PROPERTIES OF CHOLESTEROL

i) Derives its name from Greek word meaning Solid bile

ii) Occurs as a white or faintly yellow , almost colourless, pearly leaflets orgranules
iii) It is insoluble in water,sparingly solunle in alcohol and solube in ether, chloroform, hot
alcohol, ethyl acetate and vegetable oil.

It crystallizes from solution in colourless rhombic plates with one or more characteristic notches in
the corner

iv) It is not saponifiable.

v) Boiling point is 147 to 150oC.
vi) It can undergo addition reactions with halogens

SOURCES

Exogenous; From diet 0.3mg/day

Diets rich in Cholesterol are butter, cream milk

A hen`s egg weighing 2oz gives250mg cholesterol.

Endogenous; Synthesized from acetyl-CoA approx 1.0mg/day

Occurrence; Widely present in body tissues

Found in large amounts in normal human adult brain and nervous tissues 2%

, in liver 0.3%, skin 0.3%, Intestinal mucosa 0.2%.

Adrenal cortex approx 10% or more,

The high content of cholesterol in skin may be related to Vit. D formation by UV-rays; that in the
adrenal and gonads to steroid and sex hormone synthesis

FORMS OF CHOLESTEROL

Two forms abound , the free cholesterol and the ester form

In cholesterol ester the –OH in C3 position is esterified to a fatty acid; also known as bound
cholesterol.

Common fatty acids for cholesterol esterification are;

Linolenic acid---------50%

Oleic Acid------------------18%
Palmitic Acid--------------11%

Arachidonic Acid----------5%

Other fatty acids-------------16%.

Free cholesterol is equally distributed in plasma and red blood cells

Bound cholesterol (Esters) are not found in red blood cells.

In brain and nervous tissue, free forms predominate but in adrenal cortex, esters occur

ESTERIFICATION OF CHOLESTEROL

Occurs in two forms (a) Some cholesterol esters are formed by transfer of acyl groups from acyl-Co A
to cholesterol by acyl transferase

(b) Most esters are formed by plasma Lecithin cholesterol acyl transferase (LCAT). This enzyme LCAT,
transfers acyl groups ( mostly unsaturated acyl groups), from the B-position of Lecithin to cholesterol

Lecithin + Cholesterol ---------→ Lysolecithin + Cholesterol ester

LCAT

BIOMEDICAL IMPORTANCE OF CHOLESTEROL

Norum`s disease

A genetic deficiency of LCAT produces Norum`s disease marked by

Rise in free cholesterol ↑

Rise in plasma Lecithin ↑,

Fall in cholesterol ester ↓

Fall in Lysolecithin ↓ and

Fall in plasma Lipoprotein ↓

TRIACYL GLYCEROL (Triglycerides TG)

These are esters of glycerol ( the simplest trihydric alcohol) with fatty acids.
Glycerol has three –OH groups
 The carbon atoms in glycerol are designated as either 1,2 and 3 or α,B and α”.
To each of these is esterified a fatty acid
On hydrolysis, a molecule of TG yields a molecule of glycerol and three molecules of
Fatty acids
Sometimes, Fewer than three molecules of Fatty acids will be esterified to glycerol to
give
Momoacylglycerol (MG) and Diacylglycerol (DG) also known as monoglycerides and
diglycerides respectively.
Glycerol + Fatty acid ——> Monoacylglycerol
Glycerol + 2Fatty acids ——> Diacylglycerol
Glycerol + 3Fatty acids ——> Triacylglycerol

TG is otherwise referred to as neutral fat. It is the storage form of fat (energy) in the
body.
It is not found as a component of membranes
Chemical properties of Fats and Oils
A) Hydrolysis
Acid catalyzes the hydrolysis of ester
TG ——— > Glycerol + 3Fatty Acids
Simple Triglyceride ; All three –OH groups have the same fatty acid esterified to
them
Mixed Triglyceride The esterification is done with more than one type of Fatty
Acid
(B} PHYSICAL PROPERTIES OF TRIACYL GLYCEROLS
(1) They are hydrophobic and insoluble in water
(2) Oils are liquid at20oC and contains mainly unsaturated Fatty Acids or SC triacyl
glycerol.
Oils are mainly of Plant origin
(3) Fats are solid at room temperature and contains mainly saturated fatty acids.
Fats are
mainly of animal origin
(4) Hard fat has predominantly saturated LC Fatty acids eg Pig Fat
(5) Fats containing medium Chain Fatty acids or unsaturated FAs are soft fat eg
butter, coconut oil etc.

Triacyl Glycerol is the main storage form of Lipids (energy) in the adipose tissue
(C) Enzymes called Lipases hydrolyse TG in stepwise fashion to produce glycerol and 3
molecules of Fatty acids
 (D) SAPONIFICATION Alkaline hydrolysis of fats (saponification) yields glycerol and
soap
Saponification number is defined as number of mgs of potassium hydroxide
equired to saponify one gram of fat.
This is an index of molecular weight and is inversely proportional to it
Iodine number This is defined as the number of grams of iodine taken up by 100grams of
fat

It is an index of the degree of unsaturation. IT is directly proportional to the content of

unsaturated fatty acids The higher the degree of unsaturation ,the higher the iodine
number’
Rancidity of Fats

Rancidity is the development of unpleasant colour, odour and taste of fat which is indicative
of the spoilage of fat . Fats and oils can become rancid.
Hydrolytic rancidity……..due to partial hydrolysis by traces of enzymes present in naturally
occurring fats
Oxidative rancidity results from partial oxidation of unsaturated fatty acids with resultant
formation of epoxides and peroxides of smaller molecular weight fatty acids by peroxides
and free radicals. If the same process occurs in vivo cell membrane intergrity is affected and
cell death may result.
Many natural fats and oils do contain antioxidants like Vitamin E that prevents oxidative
rancidity of FAs. PUFA easily undergoes rancidity.
Repeated heating causes cyclic FAs to polymerise.
This imparts unpleasant odour and colour to oils.

WAXES
These are esters of long chain fatty acids with long chain monohydric alcohols
Found in secretions of insects, leaves and fruits of plants eg lanolin or wool fat, beewax
whales perm oil etc.

Used in cosmetics, lubricants, ointments , polishes and candles

PHOSPHOLIPIDS
These contain an alcohol, a phosphate group, fatty acids and a nitrogenous base’ They are
classified according to Calmer and Carter into three main classes based on the nature of
alcohol group they contain
Glycerophospholipids
Lipids containing glycerol, Fatty acids a nitrogenous base and a phosphoric acid moiety.
They are compound lipids

Their parent compound is phosphatidic acid eg Phosphatidylcholine (Lecithin), Phosphatidyl

ethanolamine (Cephalin) and Phosphatidylserine plasmalogen and phosphatides.
Phosphoinositides
These have inositol as their alcohol group eg Phosphatidylinositol (Lipositol)

Phosphosphingosine
These possess sphingosine (Sphingol) , an unsaturated amino alcohol as its alcohol group
Phosphatidylcholine (Lecithin)

Found in eggs, liver, brain nerve tissue, sperm, in seeds and sprouts’
Yields glycerol, fatty acids phosphoric acid and choline on hydrolysis
Αlpha- or Beta-lecithin exist depending on the position of phosphoric acid-choline complex.

Structure of Phosphatidic acid

Phosphatidic acid has Fatty acids esterified to carbon 1 and 2 of glycerol while a phosphoric
acid moiety is esterified to position 3 hydroxyl groups
Characteristics of Phospholipids
i) They are amphypathic in nature ie has water loving and water hating portions
ii) They form micelles or bilayers to keep the hydrophobic portion away from water
iii) Under appropriate conditions, a bilayer will enclose upon itself to form Liposome
iv) Liposomes are formed by sonication of a mixture of PLs. They form a vehicle for
conveyance of drugs in eg cancer chemotherapy,, proteins ,enzyme or gene
conveyance’
v) PLs form membrane bilayers driven by hydrophobic interactions

Properties

Physical properties
(i) Pure lecithin is a waxy ,white but becomes brown on exposure to air (auto-
oxidation)
(ii) It is hygroscopic
(iii) It mixes well with water to form colloidal solution
 (iv) Soluble in fat solvent but not in acetone
Chemical properties
Aqueous solution of Lecithin splits into phosphatidic acid and choline when shaken with
H2SO4
Boiled with alkalis or mineral acids ,lecithin splits into choline , two molecules of fatty acids
and glycerophosphoric acid
H2O

Lecithin ---------(H2So4)-------------→ Phosphatidic Acid + Choline

Shake

Phosphatidic Acid H2O_____________> Glycerophosphoric acid + 2 Fatty Acids

PHOSPHOLIPASES
These are enzymes that hydrolyse phospholipids. Several types of phospholipases can be
distinguished based on the way they hydrolyse phospholipids

Types of phospholipases
Phospholipase “A”
i) Present in humans and other mammalian tissues
ii) Also found in snake venom
iii) It degrades Lecithin
iv) PLipase A1 Splits FA moiety in position C1
v) Plipase A2 Splits off FA moiety in C2 and forms lysolecithin and one molecule of
FFA
Phospholipase “B”
i) Found with PhosphoLipase A in mammalian tissues
Also isolated from some fungus eg Aspergillus sp. And Penicillium notatum
ii) Has lysolecithin as its substrate
iii) Splits lysolecithin into a molecule of Fatty acid and glycerophosphocholine
(glyceryl phosphoryl choline)
Phospholipase “C”
i) Mainly found in plant kingdom
ii) Found in Clostridium welchii and in some snake venoms
 iii) Isolated from mammalian brain recently
iv) Splits lecithin into DAG and phosphocholine (Phosphoryl choline)
Phospholipase “D”

Found only in plants eg cabbage, cotton seeds, carrots etc.

Not important for human body
Splits off choline leaving phosphatidic acid
Specific Phospholipids and their Characterist

OTHER PHOSPHOLIPIDS
Phosphatidyl Ethanolamine (Cephalins)
I) Related structurally to Lecithin (Has ethanolamine replace Choline)
II) Both α- and B-Cephalins exist
III) Rich in brain and nervous tissues (occur with Lecithin)

Phosphatidyl inositol

i) Inositol is an alcohol (Hexa- hydroxycyclohexane, GF C6H12O6 )

ii) Richly occur in brain and nervous tissues
iii) Also found in soybeans and in plant phospholipids

Phosphatidyl Serine
i) A Cephalin like phospholipids
ii) Contains amino Acid Serine
iii) Found in Brain and Nervous tissues and in blood

Lysophospholipids
These are phosphoglycerides that contain only one Fatty acid in the α-position eg
Lysolecithin
Formation
They can be formed in two ways
i) By the action of Phospholipase A2
ii) Alternatively by action of Lecithin Cholesterol Acyl Transferase (LCAT)

Lecithin + Cholesterol -------→ Lysolecithin + Cholesterol Ester

 PLASMALOGENS
I) Constitutes about 10% of brain PLs ,nervous tissue, muscle and mitochondria
II) On Hydrolysis yields (a) one molecule each of long chain aliphatic aldehyde,
(b) A fatty acid,
(c) Glycerol phosphate and
(d) A nitrogenous base (Usually ethanolamine or rarely

Choline)
III) When hydrolysed the unsaturated ether in position one yields saturated
aldehyde like palmitic aldehyde or stearic aldehyde and so gives a positive
reaction when tested for aldehydes with Schiff`s reagent(Fuchsin-sulphurous acid
), after pretreatment of the phospholipid with mercuric chloride
IV) This reaction represents the condensation of the enol group of the aldehyde with
the –OH group of glycerol.

SPHINGOMYELINS (Phosphatidyl Sphingosides)

i) Largely found in brain and nervous tissues
ii) Has no glycerol but the unsaturated amino alcohol Sphingosine (Sphingol)
iii) Yields on hydrolysis;
(a) One molecule of Fatty acid,
(b) One mole of Phosphoric acid,
(c) One mole ofNitrogenous base Choline and
(d) One mole of Sphingosine.

Sphingosine + Fatty Acid ------→ Ceramide

Ceramide + Phosphate moiety -----→ Ceramide Phosphate
Sphingosin Minus Phosphate -------→ Ceramide Phosphate
Sphingomyelinase split off Choline Phosphate from Sphingomyelin to form Ceramide

CH3(CH2)12-CH=CH-CH(OH)-CH-NH-COR
I
CH2-PO2-OCH2-CH2-N+(CH3)3
Structure of Sphingomyelin
CLINICAL ASPECT

Large deposition of Sphingomyelins occur in brains , liver and spleen of patients with
Niemann-Pick disease
 NIEMANN-PICK DISEASE
I) This is a lipid storage disease ,(Lipidosis)
II) a heritable disorder of sphingomyelin metabolism
III) Here Sphingomyelin is not degraded and so accumulates
Mode of inheritance
Autosomal recessive

Enzyme Defect
Sphingomyelinase is deficient. (a lysosomal Enzyme)
Clinical Features
Effects is seen in children at birth or early Infancy

They present with;

(a) Gradual enlargement of abdomen
(b) Enlargement of the Liver (hepatomegally)
(c) Enlargement of the spleen (Splenomegally)
(d) Progressive mental deterioration (due to accumulation of sphingomyelins in brain)
(e) Other lipids and Cholesterol are usually normal or may be raised slightly.
Prognosis-------Usually Fatal , Progressive downwards course;
80% of infants die within 2 years.

PHOSPHATIDIC ACID
I) Is an intermediate in TG and PL synthesis
II) Not found in large amounts in tissues

CARDIOLIPIN
i) A PLipid found in mitochondria (inner membrane) and bacterial wall
ii) Formed from Phosphatidyl glycerol
iii) It is Diphosphattidyl glycerol
iv) On hydrolysis yields
(a) 4 mols of Fatty acids
(b) 2moles of Phosphoric acid
(c) 3mols of Glycerol
Cardiolipin is only phospholipid with antigenic properties
FUNCTIONS OF PLs
STRUCTURAL FXNS

i) PLs participate in formation of Lipoprotein complexes

ii) Are major components of all biological membranes
iii) They permit very high permeability to some molecules(hydrophobic) and
iv) Lysis by surface active agents ---detergents, bile salts etc

ROLE IN ENZYME ACTION

Some enzymes require tightly bound phospholipids for activity eg mitochondrial enzymes of
oxidative phosphorylation
Role in Blood Clotting

Conversion of prothrombin to thrombin by active factor Xand possibly the activation of

factor vIII by activated factor IX are steps in coagulation process that require phospholipids.
Platelets provide the chief source of PLs
Lipid content of Platelets that aid in blood clotting is called Platelet Factor 3
ROLE IN INTESTINAL ABSORPTION

Lecithin enhances absorption by aiding emulsification by lowering the surface tension of

water.
Aids Lipid Transport
VLDL transports endogenous lipids produced in liver Chylomicrons transports exogenous
lipids (lipids absorbed in intestine)
ELECTRON TRANSPORT
Probably PLs help to couple oxidation with phosphorylation
May also help to maintain ELetron transport enzymes in active form and in proper relative
positions.
LIPOTROPIC ACTION OF LECITHIN
Choline has lipotropic action (prevention of fatty liver)
Lecithin by providing choline helps to prevent fatty liver

Ion transport and secretion

Phosphatidic and phosphosphingosides turnover ios proportionalto the rate of secretion in
secretary cells suggesting that Pls may be implicated in secretion of hormones, enzymes,
mucins and other proteins
Source of Arachidonic acid
Phospholipase A2 hydrolyse PLs of membrane to provide unsaturated fatty acids,
arachidonic acid used in synthesis of prostaglandins and Leucotrienes
Insulation

PLs of myelin sheath provide insulation to nerve fibers

Co-factor
PLs are cofactors to Lipoprotein lipase and Triacylglycerol Lipase
Role in signal transduction

Phosphodiesterase hydrolyse Phosphatidylinositol ,4,5-P2 to myo-inositol 1,4,5-P3 and

diacylglycerol . Myoinositol P3 at 0.1-o.4µmols/L releases Ca++ ions from a variety of
organellepreparation and membranes. This way. PLs aid in signal transduction.
CLINICAL ASPECT

(a) Dipalmityl Lecithin (DPL)

This serves as a surfactant and lowers surface tension in alveoli
Alveoli has 2 types of cells
i) Type 1; Thin cells inning much of alveoli
ii) Type 11 ; Are granular pneumocytes, round cells that contain lamellar
inclusions .These inclusions contain surfactants, DPL, which is secreted by
exocytosis.Surface activity is the phenomenon whereby the surface tension
of the air-alveoliu linning interface is lowered with expiration due to presence
of DPL. In absence of normal surface activity, if DPL is absent,the alveolar
radius becomes smaller with expiration, the wall tension rises and the alveoli
collapses. Absence of DPL in premature foetus, produces collapsing of lung
alveolileading to acute respiratory distress syndrome(Hyaline-membrane
disease)
(b) Lecithin-Sphingomyelin ratio (L/S ratio)
L/S ratio in amniotic fluid is used for evaluation of foetal lung maturity. Before
34weeks of gestation, the amniotic fluid Lecithin and Sphingomyelin concentrations
are equal After this time the lecithin concentration increases remarkakly that L/S
ratio rises to greater than 5 at birth.
So L/S ratio of >2 or >5 is indicative of foetal maturity and precludes likelihood of
ARDS at birth.
Delivery of premature low birth weight foetus, with L/S ratio approximately 1 or <1 is
an indication that the infant wil likely develop ARDS or HMD
(c) ESTIMATION OF LECITHIN
Estimation of Lecithin phosphorus is adjudged to be more useful clinically
A value of 0.100mg/100dl indicates adequate foetal lung maturity.

GLYCOLIPIDS
Cerebrocydes (Glycosphingolipids)
i) Cerebrosides abound in white matter of brain and in myelin sheath of nerves
ii) Not found in brain of embryo
iii) They develop as modullation progresses
iv) In modullated nerves, the concentration of cerebrosides are much higher than in
non-medullated fibers
STRUCTURE

Cerebrosides are build on the following;

FA of high mol. weight
Sphingosine-----------------<
Usually galactose but sometimes glucose

Usually no glycerol
No Phosphoric Acid
No Nitrogenous base. Hence on hydrolysis, Cerebrosides yield:
A sugar, usually Galactose (Sometimes Glucose)
A high molecular Weight Fatty Acid and

The Alcohol Sphingosine or Dihydrosphigosine

They thus [possess Nitrogen but noNitrogenous base
TYPES OF CEREBROSIDES
Four types are distinguishable based on their Fatty Acid content

a) KERASIN; Usually contains Lignoceric acid [C23H47COOH] as fatty acid, (Synthesized

from Acetyl-CoA condensation)
b) Cerebron (Phrenosin); Contains Hydroxy Lignoceric Acid, also called Cerebronic acid
(formed by hydroxylation at C2 of Lignoceric acid)
c) Nervon; Contains unsaturated homologue of Lignoceric acid called Nervonic acid
C23H45COOH . Appears to be formed by elongation of oleic acid
d) Oxynervon ;Contains hydroxyl derivatives of nervonic acid

PSYCHOSIN
Prolonged hydrolysis of any Cerebroside with Ba(OH) 2 removes the Fatty acid to yield
psychosin ( Sphingosine + Sugar). Further hydrolysis of psychosin gives galactose and
Sphingosine
GAUCHER`S DISEASE
Is an inherited disorder of Cerebroside metabolism (Lipidosis)
Inheritance---Autosomal recessive
Enzyme Defect; Deficiency of B-Gluco-cerebrosidases, a lysosomal enzyme. This enzyme
hydrolyses gluco-cerebrosides to give Ceramide and glucose.In absence of enzyme,
cerebrosides cannot be degraded in the body and so large quantities of glucocerebrosides
accumulate in RE cells namely, Liver, Spleen, bone marrow and brain .Also complex lipids
appear to collect within the mitochondria of the RE-cells.

Biochemistry; Raised acid phosphatise levels in serum

Clinical Features
Adults and Children are affected
Onset ininfancy and childhood is acute, with rapid course and death in a matter of years.

The infant looses weight, fails to grow with progressive mental retardation
Initial spasticity is followed later by flaccidity
In Adults, spleen progressively enlarge (Splenomegaly). , May reach umbilicus.
They experience characteristic bone pain due to marrow cells replaced with histiocytes
loaded with the lipids.This leads to progressive anaemia, leucopenia andthrombocytopenia;

Increased tendency to secondary infections and haemorrhage.

GANGLIOSIDES
In 1942, Klenk isolated from beef brain, carbohydrates rich glycolipids which he called
gangliosides
Gangliosides have been isolated from ganglion cells, neuronal bodies and dendrites, spleen
and RBC stroma.
Largest accumulations are found in gray matter of brain. Gangliosides are the most complex
of all the glycosphingolipids
They are large complex Lipids with molecular weight varying from 180,000 to 250,000.
STRUCTURE
Exact structure is yet unknown.

However hydrolysis yields

a) A long chain Fatty acid
b) AlcohoSphingosine
c) A carbohydrate moiety which usually contains
i) Glucose or a Galactose
ii) At least one molecule of N-acetyl neuraminic acid (NANA) Also called
sialic acid
Brain gangliosides are known to be complex , some mono-, di-, and
trisialogangliosides containing 1-3 sialic acid residues have been described.
TYPES OF GANGLIOSIDES
Over 30 types of gangliosides have been isolated from brain tissues.. Four
important types are;

GM-1, GM-2, GM-3 and GD-3

GM-1
B-1→4 B-1→4
Gal---Gal-Nac -------→Gal-------→Glc------------→ Ceramide

B-1→3 ↓α-2→3
NANA
GM-2
B,1→4 B,1→4
Gal Nac------------------→Gal-------------------→Glc-------------→ Ceramide

↓α,2→3
NANA
GM-3
B,1→4

Gal-------------------→Glc--------------------------Ceramide
↓α,2→3
NANA
GD-3

Α,2→3 α,2→3
NANA-------------------------→NANA--------------------------→Gal
↓B,1→4
Glc

↓
Ceramide
Key
Gal Galactose
Glc Glucose

Gal Nac N-acetyl galactosamine

NANA N-acetyl neuraminic acid

CLINICAL ASPECT
GM-3is the simplest and most common glycoside found in tissues. It contains ceramide, one
molecule of glucose, one molecule of galactose and one molecule of neuraminic acid. GM-1
is a complex ganglioside derived from GM-3 and is of considerable biologic interest. It is now
known to be the receptor for cholera toxins in human intestine,
Gangliosides are amphipathic . The highly charged sugar and sialic acid section protrude on
the outer side of the membranes while the ceramide section which is hydrophobic is
embedded in the lipid core. Hence gangliosides serve as specific receptors for hormones and
so can influence cellular metabolism

TAY-SACH`S DISEASE (GM-1 Gangliosidosis)

Deficiency of Hexosaminidase causes gangliosides (of GM2 species) to accumulate in brain
and nervous tissues.
Inheritance; Autosomal recessive

Normal degradation of GM2 require that the enzyme Hexosaminidase hydrolyses off the
terminal Gal-NAc. Then other components are hydrolysed by other specific enzymes. In
absence of this enzyme, GM2 cannot be degraded and so accumulates
SYMPTOMS

It is associated with progressive development of idiocy and blindness in infants soon after
birth. This is due to widespread injury to ganglion cells in brain (cerebral cortex) and retina.
A cherry-red spot about the macula, seen ophthalmoscopically, is pathognomonic and is
caused by destruction of retinal ganglion cells, exposing the underlying vasculature.

There may be seizure and association of macrocephaly. Prognosis is bad,usually leads to

death.
GM2 GANGLIOSIDOSIS
Caused by deficiency of B-Galactosidase leading to accumulation of GM-1 gangliosides,
glycoproteins, and the glycoprotein keratin sulphate

Iheritance pattern and symptoms are similar to Tay-Sach`s disease