LIPIDS

STRUCTURE AND
CLASSIFICATION
Lipids

• Heterogeneous class of naturally occurring organic

compounds

• Classified together on the basis of common solubility

properties

• Further sub-classified according to function and structure

Lipids

• Fatty acids, triacylglycerols, sphingolipids,

phosphoacylglycerols and glycolipids

• Lipid-soluble vitamins

• Prostaglandins, leukotrienes and thromboxanes

• Cholesterol, steroid hormones and bile acids

Solubility Properties

• Insoluble in water, but soluble in organic solvents (e.g.,

diethyl ether, dichloromethane and acetone)
Functional Classification

• Storage of energy in animals

• Membrane components
• Lipid bilayer

• Messengers
• Primary: Hormones
• Secondary: mediate hormonal response (e.g., prostaglandins,
thromboxanes, etc.)
Structural Classification

• Simple lipids (e.g., fatty acids and waxes)

• Complex lipids

• Steroids

• Arachidonic acid derivatives

• Prostaglandins, thromboxanes and leukotrienes
FUNCTIONS OF LIPIDS Present in small quantities:
Major source of caloric energy Enzyme cofactors
Insulator Electron carriers
Cell membrane components Light absorbing pigments
Lipoprotein Fat soluble vitamins
Precursors of prostaglandin Intracellular messengers
Normal growth & function Hydrophobic anchors
Bioeffectors/ bioregulators
 CLASSIFICATION OF LIPIDS

Simple Lipids: Esters of fatty acids with various alcohols.

Fats - esters of fatty acids with glycerol (triacylglycerols).

Oils are fats in liquid state
Waxes - esters of fatty acids with high molecular weight monohydric
alcohols.
Compound Lipids: contain groups other than fatty acids and
alcohols.

Phospholipids - fatty acid, alcohol, phosphoric acid and a base.

Glycolipids ( Glycosphingolipids) - fatty acid, sphingosine, and CHOs.
Lipoproteins - triacylglycerides, phospholipids, cholesterol, proteins.
Lipid-linked proteins- prenylated proteins, fattyacyl-linked proteins.
Glycophosphatidyl-inositol linked proteins
Others: sulfolipids, aminolipids,
 Derived Lipids -
Fatty acids, mono- &
diacylglycerides, glycerol,
Miscellaneous Lipids -
lysophosphatides, fatty
Aliphatic hydrocarbons
aldehydes, ketone
Carotenoids
bodies, etc.
Squalene
Terpenes (isoprene units)
Steroid Lipids - Vitamins E & K
Cholesterol, cholesterol esters, Glycerol ether
Cholesterol derivatives – bile Glycosyl glycerols (plants)
acids , steroid hormones,
vitamin D, phytosterols
The Principal Classes of Storage and Membrane Lipids

Base
Fatty Acids

• Unbranched carboxylic acid chain with even number of

carbons (between 10-20 carbons) derived from hydrolysis
of animal fats, vegetable oils or membrane phospholipids

• Denoted by the formula (A:B)

• A = number of carbon atoms
• B = number of double bonds
• E.g., (18:0), (18:1) or (18:3)
FATTY ACIDS - CARBOXYLIC ACIDS WITH LONG-CHAIN
HYDROCARBON SIDE CHAINS.

- usually
biosynthesized by
the concatenation
of C2 units.
- rarely free in
nature but occur
in esterified form
as the major
components of
various lipids.
 SOME FUNCTIONS OF FATTY ACIDS

1. Fuel energy
2. Maintenance of membrane fluidity (Unsaturated f.a.)
3. Component of food oils (coconut oil, etc.)
4. Growth and development (essential fatty acids)
5. Precursor of long-chain PUFAs

• Arachidonic acid -precursor of eicosanoids (prostaglandins &

leukotrienes)
• Docosahexanoic acid (brain development)
• Eicosapentanoic acids
CLASSIFICATIONS OF FATTY ACIDS
1. According to Chain Length
Short chain 2-5 carbon atoms
Medium chain 6 - 12
Long chain 13 - 26

Some Fatty Acids (shown are number of carbons)

Acetic 2 - end product of CHO fermentation

Propionic 3 - end product of CHO fermentation by
by rumen organisms
Butyric 4 - in certain fats in small amounts
Valeric 5 (butter) also end product of
Caproic 6 CHO fermentation
Lauric 12 - coconut oil, cinnamon, palm kernel,
Myristic 14 - nutmeg, palm kernel, coconut oils
Palmitic 16
Stearic 18 - common in all animal and plant fats
2. According to bond type

Saturated fatty acids - contain single bonds

ex. Palmitic acid

Unsaturated fatty acids - contain single and double bonds.

Monoenoic or monounsaturated fatty acids ( one double bond)
ex. Palmitoleic acid ( CnH2n-1COOH )
CH3 [CH2]5 CH=CH [CH2]7 COOH

Polyenoic or polyunsaturated fatty acids ( > one double bond)

ex. Linoleic acid ( CnH2n-5COOH)
CH3 [CH2]4 CH=CH-CH2-CH=CH [CH2]7 COOH
FATTY ACID COMPOSITION OF NATURAL FOOD FATS
(%Total FA)
------------------------------------------------------------------------------------------
Saturated Unsaturated
C4-C12 C14 C16 C18 C16 & C18
------------------------------------------------------------------------------------------
Olive oil <2 <2 13 3 80
Butter 11 10 26 11 40
Beef fat <2 <2 29 21 46
THE
STRUCTURAL
FORMULAS OF
SOME C18
FATTY ACIDS
 Conformations of Fatty Acids
Saturated fatty acids
- complete freedom of rotation on Geometric Isomerism
the C-C bonds ( single bonds ) of Cis isomer
the hydrocarbon tails.
R COOH
- exist in different conformations.
- flexible C=C
- fully extended form is the most H H
thermodynamically favorable,
Trans isomer
Unsaturated fatty acids
R H
- the C=C ( double) bonds are in
CIS configuration C=C
- one or more rigid ‘KINKS’ due to H COOH
nonrotating C=C bonds, thus, bent
form for CIS isomer.
Unsaturated fatty acids contributes to membrane fluidity and permeability
3. According to Source
Nonessential fatty acids
- can be synthesized in the body
ex. Saturated and monoenoic fatty acids

Essential fatty acids

- Mammals lack the enzymes that introduce
double bonds beyond carbon 9 hence they
cannot be synthesized in the body.
ex. Linoleic, linolenic, arachidonic acid
-Dietary sources: vegetable oils (corn, peanut etc,)
The Common Biological Fatty Acids
 Short-hand Notation for Fatty Acids
Carbon atoms are numbered in two ways:
DELTA notation () - from the carboxyl ( -COOH) end.

OMEGA notation () - from the terminal methyl (-CH3) end.

/\/\/\/\/\/\/\/
()
COOH
( ) 3HC

Denote the number of carbons (X) and the number of double bonds
(Y) : (X:Y)
ex. Palmitic acid 16:0 Oleic acid 18:1 Linoleic acid 18:2

Give the number of carbons and position of double bond (indicating

delta or omega) ex. Linoleic acid 18: 2 9,12 18 : 26

Linolenic acid 18: 3 9,12,15 18 : 33

 Why are essential fatty acids important?

EFAs are directly associated with many life-sustaining

biological functions:

- maintenance of healthy cell membranes

- growth requirement (w-6)
- for healthy skin (prevents dermatitis, dry flaky skin) (w-6)
- precursor of long-chain polyunsaturated fatty acids
- for brain development (w-3)
- Visual acuity /retinal development (w-3)
- precursor of eicosanoids
- decrease risks of atherosclerosis & cardiovascular disease
(antiatheromatous effect) P/S ratio
 Omega Fatty Acids are precursors of Long-Chain
Polyunsaturated Fatty Acids or LCPUFA

 -3
(ALA) C18:3n-3

C20:5n-3

C22:6n-3
 -6

(LA) C18:2n-6

(AA) C20:4n-6
 Functions of Essential Fatty Acids (EFA) and LCPUFA
Linoleic acid a-Linolenic Acid

Arachidonic acid Eicosapentaenoic Acid

cyclooxygenase 5-lipoxygenase cyclooxygenase 5-lipoxygenase

Prostanoids Leukotrienes Prostanoids Leukotrienes

PG12 LTB4 PGI3 LTB5
TXA2 LTC4 TXA3 LTC5
PGD2 LTD4 PGD3 LTD5
PGE2 LTE4 PGF3a
PGF2a

Prostaglandins & Thromboxanes Leucotrienes

- regulate inflammatory response - muscle contractant properties
- produce pain - chemotactic properties
- induce sleep - important in allergic reactions &
-reproduction inflammation
- regulate blood coagulaltion
Prostaglandins

• Family of compounds that have the 20-carbon skeleton of

prostanoic acid

• Synthesized in response to specific physiological triggers

1
7 5 3
9
6 2
COOH
8 4

10

12 14 16 18 20
11
13 15 17 19
Prostaglandins

• Synthesis is mediated by two forms of

cyclooxygenase (COX)

• COX-1: normal physiological production of

prostaglandins

• COX-2: production of prostaglandins during

inflammation
Aspirin and NSAIDs
9
COOH

11 15
As pirin and other
Arach idon ic acid N SA ID s in hibit
this enzyme

2 O2 cyclooxygenase (COX)
O 9
COOH
PGG 2
15
O 11
OOH

O HO
9 9
COOH COOH
15 15
11 11
HO HO
OH OH
PGE2 PGF2 
Thromboxanes

• Thromboxane A2 induces platelet aggregation and

vasoconstriction

• Also inhibited by aspirin and other NSAIDs

Leukotrienes

• Occur mainly in leukocytes

• Cause muscle contractions, especially in the lungs and

thereby can cause asthma-like attacks (100 times more
potent than histamine)
 ROLE OF LCPUFA IN INFANT NUTRITION & CVD
DHA - dietary sources: marine animals and planktons,
moss, ferns, seed oils (rapeseed, soya, walnut)
– accumulates in the 3rd trimester of pregnancy
- brain development
- infant milk formulation
- visual acuity or retinal development

DHA & EPA- Antiatheromatous effect:

- LDL-cholesterol, Triglycerides
- competes w/AA as cyclooxygenase substrate
lowers thromboxane production dec. Platelet
aggregation
- associated with lower incidence of atherosclerosis
& CVD

Proper balance or ratio of w-3/w-6 in the diet is impt!

TRANS unsaturated FATTY ACIDS: GOOD or BAD ?

Total & LDL-

cholesterol

Total & LDL

cholesterol

Total & LDL

cholesterol
Present in: margarine ,breads, chips, fries , breast milk, shortening
Produced by : Hydrogenation of unsaturated fatty acids
Microorganism in the GI tract of cattle
Adverse health effects:
- Essential fatty acid balance and growth in infants.
- High maternal intake inhibits LCPUF production necessary for fetal
growth and development , visual and CNS development .
- High risk for CVD
Waxes
• High molecular-weight esters

CH2 CH2 CH2 CH2 CH2 CH2 CH2 CH2

O CH2 CH2 CH2 CH2 CH2 CH2 CH2 CH3

CH2 CH2 CH2 CH2 CH2 CH2 CH2 CH3

O CH2 CH2 CH2 CH2 CH2 CH2 CH2 CH2

• 46 carbons total for triacontyl palmitate

Fats and Oils

• Contain glycerol and

fatty acids

• Glycerol is triol

• Combined with ester

bonds
TRIACYLGLYCEROL (Fats and oils)- Fatty acid triesters of glycerol

O
ll
CH2-OH CH2- O - C- R1
O
ll
CH2-OH + 3 RCOOH CH2- O - C- R2 + 3 HOH
O
ll
CH2-OH CH2- O - C- R3
GLYCEROL FATTY ACIDS TRIACYLGLYCEROL

 Nonpolar, hydrophobic, water-insoluble substances

 Energy reservoir in animals ( stored in reduced & unhydrous form
in the adipocytes)

 This subcutaneous fat layer provides thermal insulation in some

animals (whales, seals)
 TYPES OF TRIACYGLYCEROLS

Simple triacylglycerides - one kind of fatty acid.

Ex. Tristearoyl glycerol or tristearin

Tripalmitoylglycerol ot tripalmitin
Trioleylglycerol or triolein

Mixed triacylglycerides - two or three

different types of fatty acids.
Ex. 1-Palmitoeoyl, 2-linoeoyl, 3-stearoyl glycerol
Triglycerides
Triglyceride Physical Properties

• Depend on fatty acid components

• More carbons: higher melting point

• More saturated (fewer C=C): higher melting point

Triglyceride Physical Properties

• Oils:
• More unsaturated fatty acids
• Liquid at room temperature

• Fats:
• Primarily saturated fatty acids
• Semisolids or solids at room temperature
Triglycerides

• Melting points related to 3-D shape of triglyceride

• Saturated fatty acids can pack closely together

• More London dispersion forces between chains
• Higher melting points (above room temperature)

• Unsaturated fatty acids have cis double bonds

• Bend in chain prevents close packing
• Fewer London dispersion forces between them
• Lower melting points (below room temperature)
Hydrogenation

• Can convert liquid oil to solid fat by adding H2 to double bonds

by using a catalyst

• Can control hardening to produce fats of a desired

consistency

• Margarine produced by partial hydrogenation of

polyunsaturated oils derived from corn, cottonseed, peanut
and soybean oils
Hydrogenation of Triglyceride

O
H 2 C O C (CH2 )12 CH3
catalyst
O + H2
HC O C (CH2 )6 CH 2 CH 2 (CH2 )6 CH 3
O CH CH O
H2C O C (CH2 )6 CH 2 CH 2 (CH2 )6 CH 3 H 2 C O C (CH2 )12 CH 3
CH CH O
HC O C (CH2 )6 CH 2 CH 2 (CH2 )6 CH 3
O CH 2 CH 2
H2C O C (CH2 )6 CH 2 CH 2 (CH2 )6 CH 3
CH 2 CH 2
Soaps
• Natural soaps are prepared by boiling lard or
other animal fat with NaOH, in a reaction
called saponification (Latin: sapo, “soap”)

O
O CH2 OCR saponification
RCOCH + 3 N aOH
O
CH2 OCR CH2 OH O
A triglyceride - +
CHOH + 3 RCO N a
(a triester of glycerol) Sodium soaps
CH2 OH
1,2,3-Propanetriol
(Glycerol; Glycerin)
Soaps

• Soaps clean by acting as emulsifying agents

• Soap molecules spontaneously cluster into micelles wherein:

• Long hydrophobic hydrocarbon chains cluster so as to

minimize their contact with water

• Polar hydrophilic carboxylate groups remain in contact

with the surrounding water molecules
Soaps
Soaps

• Soaps form water-insoluble salts (scum) when used in

water containing Ca2+, Mg2+ and Fe3+ ions (hard water).

- +
2 CH3 ( CH2 ) 1 4 COO Na + Ca2 +
A sodium soap - 2+
(solu ble in w ater as micelles) [CH 3 (CH )
2 14 COO ] 2 Ca + 2 Na+
Calcium salt of a fatty acid
(insoluble in w ater)
 COMPOUND LIPIDS ( Polar lipids)
PHOSPHOLIPIDS (Phosphoglycerides, Glycerophospholipids)
Structural backbone: L- Glycerolphosphoric acids

O
CH2 - OH O CH2 - O - C - R1
HO - C - H O R2 - C - O - C - H O
CH2 - O - P - OH CH2 - O*- P - O*- X
OH OH
Glycerol - 3- phosphate Glycerophospholipid

Where: R1 & R2 - fatty acid aliphatic chain

X - polar head
* - phosphodiester bonds
Glycerophospholipids

• Major phosphoacylglycerols are derived from

phosphatidic acid
• Glycerol + 2 fatty acids + phosphate

• Fatty acid attached to C-2 is always unsaturated

• Most abundant fatty acids in phosphatidic acids are

palmitic (16:0), stearic (18:0) and oleic (18:1) acids.
Glycerophospholipids

• Phosphatic acid
• Glycerol + 2 fatty acids + phosphate

• Lecithins
• Glycerol + 2 fatty acids + phosphate + choline

• Cephalins
• Glycerol + 2 fatty acids + phosphate + ethanolamine or serine
 Glycerophospholipids

Name of
N ame and Formula Glycerophosp holip id
ethan olamine cephalin
HOCH2 CH2 NH2
ch oline lecithin
+
HOCH2 CH2 N(CH3 ) 3
serine cephalin
-
HOCH2 CHCOO
+
NH3

inositol OH ph os phatidylinositol
OH
HO OH
HO OH
Glycerophospholipids

• Lecithin
choline
O
+
O P OCH2 CH 2 N(CH 3 ) 3
-
O
O CH2
lin olen ic acid
O CH

O CH2 glycerol
O
palmitic acid
Glycerolphospholipids are AMPHIPATHIC or AMPHIPHILIC
molecules with nonpolar aliphatic ‘tails’ and polar
phosphoryl-X ‘head’.
Amphiphilic or amphipatic property governs lipid aggregation
into higher order structure:
- spontaneous self assembly and self sealing.
- principle behind the formation of micelles, liposomes and bilayers.
FUNCTIONS OF PHOSPHOLIPIDS
• Major component of cell membranes
• Bioeffectors ( Phosphatidylinositol, phosphatidylcholine)
• Lung surfactant, maintains normal lung
function (dipalmitoyllecithin). Respiratory Distress
Syndrome occurs in premature infants who lack surfactant

• Detergent properties help solubilize cholesterol .

( ex. phosphatidylcholine)
• Donors of arachidonic acid for the synthesis of
prostaglandins, thromboxanes & leukotrienes
Lipid Bilayer

• Hydrophilic polar head

groups point to
aqueous environment

• Hydrophobic non-
polar tails are inside
the bilayer
Fluid Mosaic Model

•
 BIOEFFECTOR ROLE OF PHOSPHOLIPIDS

INOSITOL PHOSPHOLIPID SIGNALING PATHWAY

 GLYCOLIPIDS
SPHINGOLIPIDS - Sphingomyelins & glycosphingolipids
- derivatives of the C18 amino alcohols, sphingosine, dihydrosphingosine,
and their C16, C17, C19 & C20 homologs

CH3-[CH2]12- CH= CH- CH- CH - NH3+ CH3-[CH2]12-CH2-CH2CH- CH - NH3+

OH CH2OH OH CH2OH
Sphingosine Dihydrosphingosine

- the N-acyl fatty acid derivatives, ceramides, form the parent compounds of more abundant sphingolipids

Ceramide
O
CH3-[CH2]12- CH= CH- CH - CH - NH - C-R
OH CH2O--- X
Sphingosine
Glycolipids

• Complex lipid that contains a sugar (glucose or

galactose)

• E.g., cerebrosides found in brain and nerve synapses

(CH2 ) 1 2 CH3

a ceramide
a un it of
-D-glucop yranose HO O
H OH NHCR
HO
HO O
HO a -glycosidic bon d
H
OH
H H
Sphingolipids

• Contain sphingosine, a long-chain aminoalcohol

( CH2 ) 1 2 CH3 ( CH2 ) 1 2 CH3 ( CH 2 ) 1 2 CH3

HO HO O HO O
N H2 N HCR N HCR
O-
+
OH OH OPOCH 2 CH 2 N( CH3 ) 3
Sphingosine A ceramide
O
(an N-acylsphingosine)
A sphingomyelin
Sphingolipids

• Found in the myelin sheath of nerve axons

• Multiple sclerosis - sphingomyelin deterioration

 SPHINGOMYELINS ( Sphingophospholipids)
- ceramide + phosphocholine or phosphoethanolamine

- most common and

abundant

- present in most
animal cell
membranes (myelin
sheath).
CEREBROSIDES - the simplest sphingoglycolipids (or
glycosphingolipids).
ceramide + a single sugar residue for a head group

Ex. Galactocerebroside -
most prevalent in the
neuronal cell membranes of
the .brain.
Glucocerebroside -
occurs in the membrane of
other tissues

- no phosphate grp,
- nonionic or electrically neutral
cpds.
SULFATIDES- some cerebrosides are sulfated at the C3 of
the sugar.

GLOBOSIDES - cerebrosides with two or more sugar

residues.

GANGLIOSIDES - ceramide + oligosaccharides + at least one

sialic acid (N-acetylneuraminic acid)

- over 60 ganglioside structures are known.

- primarily components of cell surface membranes
- constitute significant fraction (6%) of the brain lipid
Some Physiological and Medical Significance of Gangliosides

 Their complex CHO head grp act as receptors for certain pituitary
glycoprotein hormones that regulate a number of key physiological
functions.

 Receptors for bacterial protein toxins such as cholera toxin.

 Specific determinants of cell-cell recognition (role in growth and

differentiation of tissues as well as in carcinogenesis)

 Sphingomyelins are found in nerve and brain tissue where they

serve as electrical insulators

 Disorders of ganglioside breakdown are responsible for several

hereditary sphingolipid storage diseases. ( Tay-Sachs disease)
Steroids

• Have steroid ring structure in plants and animals

• E.g., cholesterol

C D

A B
HO
Cholesterol

• Most abundant and most important steroid in the human

body

• Component in animal plasma membranes

• Precursor of all steroid hormones and bile acids

 CHOLESTEROL

 Structural
components of cell
membranes and
plasma lipoprotein
(LDL, HDL)
 Associated with
athroslerosis
- Steroid nucleus , a derivative of
perhydrocyclopentano phenanthrene ring  Precursor of bile
. acids and steroid
hormones :
- Planar conformation with two angular - (Glucocortecoids , ,
CH2 grps. At C10 and C13. ,Mineralocortecoids
Beta configuration - above the ring ,Sex hormones)
Alpha configuration - below the ring
Cholesterol modifies membrane
fluidity:
below Tm* – interferes with HC tails of
fatty acids  inc fluidity
above Tm – limits disorder, being more
rigid than HC tails  dec
fluidity

*Tm - phase transition temperature

 Phase
transition
temperature
(Tm) of Lipids
in Membranes
(from ordered
to disordered
state)
Lipoproteins

• Transport cholesterol along with fats

Composition (% dry w eight)
Cholesterol Ph os pho- Tri-
Lip op rotein Proteins and esters lipids glycerides
High-dens ity 33 30 29 8
lipoprotein (HD L)
Low -dens ity 25 50 21 4
lipoprotein (LD L)
Very-low den sity 10 22 18 50
lipoprotein (VLD L)
Chylomicron s 1-2 8 7 84
Lipoproteins

• Protein has higher density than lipid

• HDL (high density lipoprotein)

• Higher protein to lipid ratio

• LDL (low density lipoprotein)

• Lower protein to lipid ratio
Cholesterol Transport

Dietary lipids → carried by chylomicrons to liver → liver

produces VLDL → VLDL undergoes lipolysis becoming LDL
→ LDL is absorbed by cells → Excess cholesterol is
removed by HDL from cells via reverse cholesterol
transport
Hypercholesterolemia

• Exceeding normal plasma cholesterol levels (175 mg/100

ml)

• Results from not having enough LDL receptors

• Statin drugs inhibit the synthesis of cholesterol

Atherosclerosis

• Cholesterol forms plaque deposits inside of blood vessels

• Narrows blood vessel diameter leading to lower blood

flow

• Can lead to heart attack, stroke, kidney dysfunction or

other problems
Steroid Hormones

• Androgens
• Male sex hormones synthesized in the testes
• Responsible for development of male secondary sex
characteristics
H3 C OH H3 C O

H3 C H3 C

O HO
Testosteron e And rosterone
Steroid Hormones

• Synthetic anabolic steroids

H3 C CH3 H3 C OH H3 C O
OH
H3 C
H3 C CH3 H3 C

O O O
Meth andienone Methenolone 4-And rosten e-3,17-dion e
Steroid Hormones
• Estrogens
• Female sex hormones synthesized in the ovaries
• Responsible for development of female secondary sex
characteristics and control of the menstrual cycle
CH3
H3 C C=O H3 C OH

H3 C

O HO
Proges terone Estradiol
Steroid Hormones

• Progesterone-like analogs used in oral contraceptives

CH3
N
H3 C H3 C OH C CCH
3
"N or"refers to
the absen ce of a
meth yl group here H C OH
3 C CH

O
Mifep ristone
(RU 486)
O
N orethind rone
Steroid Hormones
• Glucorticoid
hormones
CH 2 OH
• Synthesized in the OH
C=O
adrenal cortex O CH
• Regulate H3 C H
carbohydrate
metabolism H H
• Involved in reaction O
to stress Aldosterone

• Decrease
inflammation
Bile Salts

• Oxidation products of cholesterol

• Synthesized in the liver, stored in the gallbladder, and

secreted into the intestine where they emulsify dietary fats
and aid in their absorption and digestion
 Bile Salts
O O
HO NH HO NH
COO-
SO3 2 -

HO OH HO OH
Glycoch olate Taurocholate
(from glycine) (from taurine)