Lipids

Types of Lipids
Fatty Acids
Fats, and Oils
Chemical Properties of Triglycerides

Introduction
Definition: water insoluble compounds
Most lipids are fatty acids or ester of fatty acid
They are soluble in non-polar solvents such as
petroleum ether, benzene, chloroform

Functions

Energy storage
Structure of cell membranes
Thermal blanket and cushion
Precursors of hormones (steroids and prostaglandins)

Types:
Fatty acids
Neutral lipids
Phospholipids and other lipids

Fatty acids
Carboxylic acid derivatives of long
chain hydrocarbons
Nomenclature (somewhat confusing)
Stearate stearic acid C18:0 noctadecanoic acid

General structure:
CH3

(CH2)n COOH

n = 0 : CH3COOH n = 1 : propionic acid

n is almost always even

Fatty acids
Common fatty acids
n = 4 butyric acid (butanoic acid)
n = 6 caproic acid (hexanoic acid)
n = 8 caprylic acid (octanoic acid)
n = 10 capric acid (decanoic acid)

Fatty acids
common FAs:
n = 12: lauric acid (n-dodecanoic acid; C12:0)
n = 14: myristic acid (n-tetradecanoic acid; C14:0)
n = 16: palmitic acid (n-hexadecanoic acid; C16:0)
n = 18; stearic acid (n-octadecanoic acid; C 18:0)
n = 20; arachidic (eicosanoic acid; C20:0)
n= 22; behenic acid
n = 24; lignoceric acid
n = 26; cerotic acid

Types of Lipids
Lipids with fatty acids
Waxes
Fats and oils (trigycerides)
Phospholipids
Sphingolipids
Lipids without fatty acids
Steroids
6

Fatty Acids
Long-chain carboxylic acids
Insoluble in water
Typically 12-18 carbon atoms (even
number)
Some contain double bonds

corn oil contains 86%

fatty acids and 14%
acids

unsaturated
saturated fatty

Fatty acids
Fatty acids can be classified either as:
saturated or unsaturated
according to chain length:

short chain FA: 2-4 carbon atoms

medium chain FA: 6 10 carbon atoms
long chain FA: 12 26 carbon atoms
essential fatty acids vs those that can be
biosynthesized in the body:
linoleic and linolenic are two examples of essential
fatty acid

Saturated and Unsaturated

Fatty Acids
Saturated = CC bonds
Unsaturated = one or more C=C
bonds
COOH
palmitic acid, a saturated acid
COOH
palmitoleic acid, an unsaturated fatty acid
9

Structures
Saturated fatty acids
Fit closely in regular pattern
COOH
COOH
COOH

Unsaturated fatty acids

Cis double bonds
H

C C

cis double bond

COOH
10

Properties of Saturated
Fatty Acids
Contain only single CC bonds
Closely packed
Strong attractions between chains
High melting points
Solids at room temperature

11

Properties of Unsaturated
Fatty Acids
Contain one or more double C=C
bonds
Nonlinear chains do not allow
molecules to pack closely
Few interactions between chains
Low melting points
Liquids at room temperature

12

Stearic acid is saturated and would

have a higher melting point than
the unsaturated fatty acids.
Linoleic has two double bonds, it
would have a lower mp than oleic
acid, which has one double bond.
stearic acid mp 69C
oleic acid
mp 13C
linoleic acid mp -17C
13

14

Neutral lipids
Glycerides (fats and oils) ; glycerides
Glycerol
CH2OH
H

OH
CH2OH

OH
OH
OH

glycerol is a prochiral molecule

Ester of glycerol - mono glycerides,

diglycerides and triglycerides

Waxes simple esters of long chain alcohols

GLYCERIDES
O

O
O

OH

OH

OH

R
R
R
O

MONOGLYCERIDE

DIGLYCERIDE

O
TRIGLYCERIDE

Function: storage of energy in compact form and cushioning

Fats and Oils

Formed from glycerol and fatty acids
O
CH2 OH
CH

OH

CH2

OH

glycerol

HO C
O
+

(CH2)14CH3

HO C (CH2)14CH3
O
HO C

(CH2)14CH3

palmitic acid (a fatty acid)

17

Triglycerides
(triacylglcerols)
Esters of glycerol and fatty acids
ester bonds
O
CH2

(CH2)14CH3 + H2O

O
CH
CH2

O
O

C (CH2)14CH3
O
C

+ H 2O

(CH2)14CH3 +

H 2O
18

Stereospecific numbering
Carbon 2 of triglycerides is frequently
asymmetric since C-1 and C-3 may be
substituted with different acyl groups
By convention we normally draw the
hydroxyl group at C-2 to the left and use the
designation of sn2 for that particular
substituent
C-1 and C-3 of the glycerol molecule become
sn1 and sn3 respectively

Fatty acid reactions

salt formation
NaOH

RCO2H

RCO2-Na+ (a soap)

ester formation
-H20

R'OH + RCO2H

RCO2R'

lipid peroxidation
R'

O2

R
H

non-enzymatic

R'
OOH
very reactive

Lipid peroxidation
a non-enzymatic reaction catalyzed by
oxygen
may occur in tissues or in foods
(spoilage)
the hydroperoxide formed is very reactive
and leads to the formation of free radicals
which oxidize protein and/or DNA (causes
aging and cancer)

principle is also used in drying oils

(linseed, tung, walnut) to form hard films

Properties of Triglycerides
Hydrogenation
Unsaturated compounds react with H2
Ni or Pt catalyst
C=C bonds
CC bonds

Hydrolysis
Split by water and acid or enzyme
catalyst
Produce glycerol and 3 fatty acids
22

Hydrogenated fats
hydrogenation leads to either
saturated fats and or trans fatty acids
the purpose of hydrogenation is to
make the oil/fat more stable to
oxygen and temperature variation
(increase shelf life)
example of hydrogenated fats: Crisco,
margarine

Hydrogenation
O
CH2 O

(CH2)5CH CH(CH2)7CH3

O
CH

CH2

C (CH2)5CH CH(CH2)7CH3
O
C

+ 3 H2

Ni

(CH2)5CH CH(CH2)7CH3

24

Product of Hydrogenation
O
CH2

(CH2)14CH3

O
CH
CH 2

O
O

C (CH2)14CH 3
O
C

(CH2)14CH3

Hydrogenation converts double bonds in oils to single bonds. The solid products are used to make margarine and other hydrogenated items.

25

Hydrolysis
Triglycerides split into glycerol and
three fatty acids (H+ or enzyme
catalyst)
O
CH 2

(CH2)14CH3

O
CH
CH2

O
O

C (CH2)14CH 3
O
C

H+
+3 H2O

(CH2)14CH3
CH2 OH
CH

OH

CH2

OH

O
+

3 HO C

(CH2)14CH3
26

Saponification and Soap

Hydrolysis with a strong base
Triglycerides split into glycerol and
the salts of fatty acids
The salts of fatty acids are soaps
KOH gives softer soaps

27

Saponification
O
CH2 O

C (CH2)16CH3
O

CH

CH2

C (CH2)16CH3 + 3 NaOH
O
C

(CH2)16CH3

CH2 OH
CH
CH2

+OH + 3 Na O C (CH2)14CH3
salts of fatty acids (soaps)
OH
28

Analytical methods to evaluate

lipids

saponification number
iodine value (Hanus method)
free fatty acids
acetyl number
Reichert-Meissl number
HPLC/GC (for more precise analysis)

Saponification number
gives some clue as to the average
size of fatty acids in a given sample
of fat
defined as the number of milligrams
of KOH needed to neutralize the fatty
acids in 1 Gm of fat
butter (large proportion of short chain FAs)
sap. no. 220 230
oleomargarine (long chain FAs) sap. No is
195 or less

Iodine number
H

I2

I
H

I
H

measures the degree of unsaturation in a

given amount of fat or oil
the iodine number is the number of grams
of iodine absorbed by 100 grams of fat
Cottonseed oil: 103 111
Olive oil: 79 88
Linseed oil: 175 202

frequently used to determine adulteration

of commercial lots of oils

Acetyl number
some fatty acids have hydroxyl
groups
OH

H3 C

(CH2)21 CH COOH

OH
H 3C

(CH2)5

cerebronic acid

CH CH2 CH CH

(CH2)7 COOH

ricinoleic acid

The acetyl number gives the proportion of these hydroxylcontaining fatty acids in a given sample of fat or oil
acetic anhydride
fatty acid
OH

fatty acid

fatty acid
O C

OH

CH3

O
acetylated fatty acid
titrate with standardized
KOH

H3C

COOH

Acetyl number
the acetyl number is the number of
milligrams of KOH needed to
neutralize the acetic acid of 1 Gm of
acetylated fat
examples:

castor oil 146 150

cod liver oil 1.1
cottonseed oil 21 25
olive oil 10.5
peanut oil 3.5

Reichert Meissl number

Measures the amount of volatile fatty
acids (low MW and water soluble FAs)
R-M number is the number of
milliliters of 0.1N alkali required to
neutralize the soluble fatty acids
distilled from 5 Gm of fat
Butter fat has a high R-M number

WAXES
simple esters of fatty acids (usually saturated
with long chain monohydric alcohols)
O
H3C

(CH2)14

CH2

(CH2)28-CH3

fatty acid
long chain alcohol

Beeswax also includes some free alcohol and fatty acids

Spermaceti contains cetyl palmitate (from whale oil) useful for
Pharmaceuticals (creams/ointments; tableting and granulation)
Carnauba wax from a palm tree from brazil a hard wax used on
cars and boats

Spermaceti source

Carnauba wax source

Bees wax

Waxes
(CH2)14 CH2-OH

cetyl alcohol

H 3C

(CH2)24 CH2-OH

hexacosanol

H 3C

(CH2)28 CH2-OH

triacontanol (myricyl alcohol)

H 3C

Examples of long chain monohydric alcohols

found in waxes

Phospholipids
the major components of cell membranes
phosphoglycerides
O

glycerol

fatty acids (hydrophobic tail)

R'
O-

P
O

phosphate

Phospholipids are generally composed of FAs, a nitrogenous base, phosphoric

acid and either glycerol, inositol or sphingosine

glycerol

fatty acids (hydrophobic tail)

R'
O-

P
O

phosphate

X = H (phosphatidic acid) - precursor to other phospholipids

X = CH2-CH2-N+(CH3)3 phosphatidyl choline
X = CH2-CH(COO-)NH3+ phosphatidyl serine
X = CH2-CH2-NH3+ phosphatidyl ethanolamine

Sphingolipids
Based on sphingosine instead
of glycerol

OH
OH
NH2

sphingosine

HO

long chain hydrocarbon

NH2

attach fatty acid here

OH

attach polar head group here

Sphingomyelin
R

HO

O
NH

R'

usually palmitic acid

OO

O
P

N(CH3)+

O
phosphatidyl choline (also can be ethanolamine)

Ether glycerophospholipids
Possess an ether linkage instead of an acyl group
at the C-1 position of glycerol
PAF ( platelet activating factor)
A potent mediator in inflammation,
allergic response and in shock (also
responsible for asthma-like symptoms)
Plasmalogens: cis ,-unsaturated ethers

Ether glycerophospholipids
O
-O

P
O

H2C
O

CH

CH3
O

CH2

CH2

CH3

CH3

CH2

H2C

O
C

-O

CH

CH2

CH2

N
CH3

CH2

O
C

CH3

CH3

platelet activating factor or PAF

A choline plasmalogen

CH3

glycolipids

HO

O
NH
O

R'
SUGAR

polar head is a sugar

beta linkage
There are different types of glycolipids: cerebrosides, gangliosides,
lactosylceramides

GLYCOLIPIDS
Cerebrosides
One sugar molecule
Galactocerebroside in neuronal membranes
Glucocerebrosides elsewhere in the body

Sulfatides or sulfogalactocerebrosides
A sulfuric acid ester of galactocerebroside

Globosides: ceramide oligosaccharides

Lactosylceramide
2 sugars ( eg. lactose)

Gangliosides
Have a more complex oligosaccharide attached
Biological functions: cell-cell recognition;
receptors for hormones

Gangliosides
complex glycosphingolipids that
consist of a ceramide backbone with
3 or more sugars esterified,one of
these being a sialic acid such as Nacetylneuraminic acid
common gangliosides: GM1, GM2, GM3,
GD1a, GD1b, GT1a, GT1b, Gq1b

CH2OH

CH2OH

OH

OH

H
H

CH2OH

CH2OH

OH
O

OH

NH
C

D-Galactose

H3C

OH

HO

O
O

COO-

OH

N-acetylneuraminidate (sialic acid)

O
H
C

CH2

NH

C
C
H

CHOH
CH2OH

A ganglioside (GM1)

OH
H
C

CHOH
H

H
H

C NH

OH

CH3
O

D-glucose

D-galactose

N-Acetyl-D-galactosamine

Cardiolipids
O
O
R2

H 2C

H 2C

P
OH

O
R1

R4
H

CH2 C

CH2 O

OH

CH2

CH2

O
O

R3

OH
glycerol

glycerol

glycerol

A polyglycerol phospholipid; makes up 15% of total lipid-phosphorus

content of the myocardium associated with the cell membrane
Cardiolipids are antigenic and as such are used in serologic test for
syphilis (Wasserman test)

Sulfolipids
also called sulfatides or cerebroside
sulfates
contained in brain lipids
sulfate esters of cerebrosides
present in low levels in liver, lung,
kidney, spleen, skeletal muscle and
heart
function is not established

Lipid storage diseases

also known as sphingolipidoses
genetically acquired
due to the deficiency or absence of a
catabolic enzyme
examples:

Tay Sachs disease

Gauchers disease
Niemann-Pick disease
Fabrys disease

Blood groups
determined by various glycolipids on RBCs
A antigens
AcN

Gal

Ac
N

Glu-sphingosine

L-Fucose

B antigens
Gal

Gal

NAc-Glu-sphingosine

L-Fucose

H antigens

Gal

NAc--Glu-sphingosine
L-Fucose

not recognized by anti-A or anti-B antibodies

(found on type O blood cells)

52

53

54

55

56

Cholesterol and cholesterol

esters
H3 C
CH3
H

CH3

hydrophobic
O

H
OH

H
drawn this way

R
usually palmitate

hydrophillic

STEROID NUMBERING
SYSTEM
18

1
2
A
3
4

11
19

12

17

C 13

14

9
10
B 8
7

5
6

16
15

Cholesterol sources, biosynthesis and

degradation

diet: only found in animal fat

biosynthesis: primarily synthesized in the liver
from acetyl-coA; biosynthesis is inhibited by LDL
uptake
degradation: only occurs in the liver

Cholesterol and cholesterol

esters

HO
Functions: -serves as a component of membranes of cells (increases or
moderates membrane fluidity
-precursor to steroid hormones
-storage and transport cholesterol esters

61

Prostaglandins and other

eicosanoids
local hormones, unstable, key mediators of
inflammation
derivatives of prostanoic acid

COOH
20

12
prostanoic acid

Functions of eicosanoids
Prostaglandins particularly PGE1 block
gastric production and thus are gastric
protection agents
Misoprostol (Cytotec) is a stable PGE1
analog that is used to prevent ulceration
by long term NSAID treatment
PGE1 also has vasodilator effects
Alprostadil (PGE1) used to treat infants with
congenital heart defects
Also used in impotance (Muse)

Leukotrienes
Leukotrienes are derived from arachidonic acid via the enzyme
5-lipoxygenase which converts arachidonic acid to 5-HPETE
(5-hydroperoxyeicosatetranoic acid) and subsequently by
dehydration to LTA4

OH

OH

COOH

COOH
H
C5H11

H
S

C5H11

Cys
gGlu
LEUKOTRIENE F4 (LTF 4)

peptidoleukotrienes

S
Cys

Gly

gGlu
LEUKOTRIENE C4 (LTC 4)

SUMMARY OF ABOVE DONE THINGS

65

Lipid-linked proteins
Lipid-linked proteins (different from
lipoproteins)
lipoproteins that have lipids covalently
attached to them
these proteins are peripheral membrane
proteins

Lipid-linked proteins
3 types are most common:
Prenylated proteins
Farnesylated proteins (C15 isoprene unit)
Geranylgeranylated proteins (C20 isoprene
unit)

Fatty acylated proteins

Myristoylated proteins (C14)
Palmitoylated proteins (C16)

Lipid-linked proteins
glycosylphosphatidylinositol-linked
proteins (GPI-linked proteins)
occur in all eukaryotes, but are
particularly abundant in parasitic
protozoa
located only on the exterior surface of
the plasma membrane

Fatty acylated proteins

Prenylated proteins

GPI-linked proteins

Lipoproteins
particles found in plasma that
transport lipids including cholesterol
lipoprotein classes
chylomicrons: take lipids from small
intestine through lymph cells
very low density lipoproteins (VLDL)
intermediate density lipoproteins (IDL)
low density lipoproteins (LDL)
high density lipoproteins (HDL)

Lipoprotein
class

Density
(g/mL)

Diameter
(nm)

Protein % Phosphol
of dry wt ipid %

Triacylglycerol
% of dry wt

HDL

1.063-1.21

5 15

33

29

LDL

1.019
1.063

18 28

25

21

IDL

1.006-1.019

25 - 50

18

22

31

VLDL

0.95 1.006

30 - 80

10

18

50

chylomicrons

< 0.95

100 - 500

1-2

84

Composition and properties of human lipoproteins

most proteins have densities of about 1.3 1.4 g/mL and lipid aggregates usually
have densities of about 0.8 g/mL

Lipoprotein structure

75