Download Lipids and Membranes

LIPIDS
What are Lipids?




Class of biomolecules that are all water insoluble
No defining characteristic except that all of them
share the same trait: non-polar
Most common are fatty acids and esters of fatty
acids
Functions
 Energy
Storage
 Cell membrane
 Thermal blanket and cushion
 Precursors of hormones
Fatty Acids



Fatty acids consist of a hydrocarbon chain with a
carboxylic acid at one end.
A 16-C fatty acid:
CH3(CH2)14-COONon-polar polar
General Structure:
CH3
(CH 2)n COOH
n = 0 : CH 3COOH n = 1 : propionic acid
n is almost always even
Fatty Acids



Double bonds in fatty acids usually have the cis
configuration.
Most naturally occurring fatty acids have an even
number of carbon atoms.
IUPAC naming:
 COOH
carbon as C1
 Farthest carbon is ω
 Total carbons/# double bonds/Δdouble bond position
Fatty Acids

Some fatty acids and their common names:
14:0 myristic acid; 16:0 palmitic acid; 18:0 stearic acid;
 18:1 cisD9 oleic acid
 18:2 cisD9,12 linoleic acid
 18:3 cisD9,12,15 a-linonenic acid
 20:4 cisD5,8,11,14 arachidonic acid
 20:5 cisD5,8,11,14,17 eicosapentaenoic acid (an omega-3)


Essential fatty acids
ALA- ω-3 FA precursor for EPA and DHA
 LA – ω-6 FA precursor of AA

Fatty Acid Chemistry

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
Drying Oils: Application of
Peroxidation


based on the ease of autoxidation and polymerization of
oils (important in paints and varnishes)
the more unsaturation in the oil, the more likely the
“drying” process
 Non-drying

oils:
Castor, olive, peanut, rapeseed oils
 Semi-drying

Corn, sesame, cottonseed oils
 Drying

oils
oils
Soybean, sunflower, hemp, linseed, tung, oiticica oils
Fatty Acid Chemistry

Transesterification
 Acid-catalyzed
exchange betweein R groups of esters
 Frequently-used in polyester, methanolysis and
biodiesel industries
Fatty Acid Chemistry

Hydrogenation
 Reduces
double bonds on unsaturated fatty acids
 Prevents oils from going rancid
Fatty Acid Chemistry

Saponification
 Base
hydrolysis of
triglycerides to produce
fatty acid salts

𝑠𝑎𝑝𝑜𝑛𝑖𝑓𝑖𝑐𝑎𝑡𝑖𝑜𝑛 𝑛𝑢𝑚𝑏𝑒𝑟 =
 High
𝑚𝑔 𝐾𝑂𝐻
𝑔 𝑓𝑎𝑡
saponification number,
shorter chain length
Soaps

Types of soaps:
Sodium soap – ordinary hard soap
 Potassium soap – soft soap (shaving soaps are potassium
soaps of coconut and palm oils)
 Castile soap – sodium soap of olive oil
 Green soap – mixture of sodium and potassium linseed oil
 Transparent soap – contains sucrose
 Floating soap – contains air
 Calcium and magnesium soaps are very poorly water
soluble (hard water contains calcium and magnesium salts –
these insolubilize soaps)

Fatty Acid Chemistry

Iodine Number


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
H
H
I2
I
H
I
H
Fatty Acid Chemistry

Acetyl Number
 the
number of milligrams of KOH needed to neutralize
the acetic acid of 1 g of acetylated fat
acetic anhydride
fatty acid
OH
fatty acid
fatty acid
O C
OH
CH3
+
O
acetylated fatty acid
titrate with standardized
KOH
H3C
COOH
Fatty Acid Chemistry

Reichert-Meisl Number
 measures
the amount of volatile fatty acids (low MW
and water soluble Fas)
 the 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
 Indicator of non-fat compounds in edible fats, or
volatile fatty acids
Fats and Oils





fats are solids or semi solids
oils are liquids
melting points and boiling
points are not usually sharp
(most fats/oils are mixtures)
when shaken with water, oils
tend to emulsify
pure fats and oils are colorless
and odorless (color and odor is
always a result of
contaminants) – i.e. butter
(bacteria give flavor, carotene
gives color)
Waxes

simple esters of fatty acids
(usually saturated with long
chain monohydric alcohols)
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

O
H3C
(CH 2)14
C
O
CH 2
(CH 2)28-CH 3
fatty acid
long chain alcohol
Spermaceti source
Carnauba wax source
Bee’s wax
Glycerides

Function
 Storage
of energy
 Cushions
O
O
O
O
O
R
O
OH
OH
OH
O
R
R
R
O
MONOGLYCERIDE
DIGLYCERIDE
O
R
O
R
O
O
TRIGLYCERIDE
Triglycerides


Esters of fatty acids and glycerol
Constituent of fats and oils
Phosphoglycerides



aka glycerophospholipids
Major constituent of cell
membranes
Structure




Glycerol backbone with
esterifies fatty acids at C1
and C2
Fatty acids are usually nonidentical
Phosphate group attached
to C1
A polar group is usually
esterified to Pi (usually
serine, choline,
ethanolamine, glycerol, or
inositol
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
Phosphoglycerides

Structure=Function
region – glycerol,
phosphate group, X
 Nonpolar region – fatty
acid
 Amphiphatic character
 Ideal for forming bilayers
polar
 Polar
"kink" due to
double bond
non-polar
Phosphoglyceride
Phosphatidyl inositol


Inositol as a polar head group
Has roles in cell signaling as well as a cell membrane
component
O
O
R1
C
H2C
O
O
CH
H2C
C
R2
O
O
P
O
O
H
OH
OH
H
OH
phosphatidylinositol
OH
H
H
H
H
OH
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 symptom
 The ether linkage is stable in
either acid or base


Plasmalogens: cis a,bunsaturated ethers

The alpha/beta unsaturated
ether can be hydrolyzed more
easily
Sphingolipids



derivatives of the lipid
sphingosine, which has a long
hydrocarbon tail, and a
polar domain that includes
an amino group
Like phosphoglycerides, are
also constituents of cell
membranes
Can be reversibly
phosphorylated and utilized
as signaling molecule
Sphingolipid Derivatives


Ceramide - amino group of
sphingosine forms an amide
bond with a fatty acid
carboxyl
Sphingomyelin has a
phosphocholine or
phosphethanolamine head
group.
common constituent of plasma
membranes
 similar in size and shape to
the glycerophospholipid
phosphatidyl choline

OH
H2C
O
OH
H
C
CH
NH
CH
C
R
ceramide
HC
(CH2 )12
CH3
Sphingolipid Derivatives



Cerebroside a sphingolipid
(ceramide) with a monosaccharide
such as glucose or galactose as
polar head group.
Ganglioside – a ceramide with
polar head group that is a
complex oligosaccharide, including
the acidic sugar derivative sialic
acid
Both are collectively known as
glycosphingolipids and are
commonly found on the outer
leaflet of the cell membrane
CH2OH
O
OH
H
OH
H
H
H
OH
O
H
H2C
OH
O
cerebroside with
-galactose head group
H
C
CH
NH
CH
C
R
HC
(CH2 )12
CH3
Ganglioside Structure
Ganglioside

Cerebrosides

One sugar molecule



Sulfatides or sulfogalactocerebrosides


A sulfuric acid ester of galactocerebroside
Globosides: ceramide oligosaccharides

Lactosylceramide


Galactocerebroside – in neuronal membranes
Glucocerebrosides – elsewhere in the body
2 sugars ( eg. lactose)
Gangliosides


Have a more complex oligosaccharide attached
Biological functions: cell-cell recognition; receptors for hormones
Cardiolipids


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)
O
O
R2
C
O
H2C
O
C
C
H
O
H2C
O
P
OH
O
R1
R4
H
O
CH 2 C
CH 2 O
OH
C
O
CH 2
O
H
C
P
O
CH 2
O
O
C
R3
OH
glycerol
glycerol
glycerol
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
Lipid Storage Diease




a group of inherited metabolic disorders in which
harmful amounts of fatty materials (lipids)
accumulate in various tissues and cells in the body
also known as sphingolipidoses
genetically acquired
due to the deficiency or absence of a catabolic
enzyme
 Tay
Sachs disease
 Gaucher’s disease
 Niemann-Pick disease
 Fabry’s disease
Tay Sachs Disease
Fabry’s Disease
Niemann Pick Disease
Cholesterol and related compounds
Cholesterol

an important constituent of cell
membranes, has a rigid ring
system and a short branched
hydrocarbon tail.





HO
Cholesterol
serves as a component of
membranes of cells (increases or
moderates membrane fluidity)
precursor to steroid hormones and
bile acids
storage and transport –cholesterol
esters
Cholesterol is largely hydrophobic.
But it has one polar group, a
hydroxyl, making it amphipathic.
PDB 1N83
cholesterol
Steroid Ring System
18
11
19
1
2
A
3
17
C 13
D
14
9
10
8
B
7
5
4
12
6
16
15
Eicosanoids




Includes prostaglandins and related compounds
Derivatives of arachidonic acid
Serves as local hormones and intercellular signaling
Key hormones in inflammation response
9
8
COOH
20
11 12
15
prostanoic acid
Eicosanoids

Types of Eicosanoids
Prostaglandins
 Prostacyclins
 Thromboxanes
 Leukotrienes
 epoxyeicosatrienoic
acids.


Biological Functions
Inflammation
 Fever
 regulation of blood
pressure
 blood clotting
 immune system
modulation
 control of reproductive
processes and tissue
growth
 regulation of the
sleep/wake cycle

Terpenes





simple lipids, but lack
fatty acid component
formed by the
combination of 2 or
more molecules of 2methyl-1,3-butadiene
(isoprene)
monoterpene (C-10) –
made up of 2 isoprene
units
sesquiterpene (C-15) –
made up of 3 isoprene
units
diterpene (C-20) –
made up of 4 isoprene
units
CHO
OH
menthol
citronellal
limonene
HO
H
squalene
lanosterol
camphene
Terpenes

tetraterpenes (C-40) are not
as common as mono, di, and
triterpenes



include the carotenoids such as
beta-carotene (precursor of
vitamin A) and lycopene found
in tomatoes
usually colorful compounds due
to highly conjugated system
polyisoprenoids or polyprenols
consist of numerous isoprene
adducts (8 – 22)

examples include dolichol
phosphate, undecaprenyl
alcohol (bactoprenol) and the
side chains of vitamins K,
vitamin E and coenzyme Q
Lipid-linked proteins and
Lipoproteins
Lipid-linked proteins



Proteins that have lipids covalently bonded to them
Usually found in cell membranes
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)


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
Lipoprotein
class
Density
(g/mL)
Diameter (nm)
Protein %
of dry wt
Phospholip Triacylglycerol %
id %
of dry wt
HDL
1.063-1.21
5 – 15
33
29
8
LDL
1.019 –
1.063
18 – 28
25
21
4
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
7
84